updated
A DNA sequence is
not a genome

Conclusion

See also page:

Independent origin
and the facts of life
(a general overview)

Contents of this page

A seductive computer experiment

Searching for exons, ignoring introns (and non-coding DNA)

Eukaryotes with intronless genes, prokayotes with introns

A static versus a dynamic genome

A DNA sequence is not a genome

• A DNA sequence is not a genome
  Without a genetic code a DNA sequence itself is just a meaningless polymer. The genetic code specifies how DNA is translated into proteins. Given that there are 4 different bases in DNA and that they are read in triplets, it follows that there are 64 different triplets. Those 64 triplet codons are translated into 20 amino acids. That is the genetic code. The most remarkable fact is that all living creatures on earth have the same genetic code! One of the most profound questions one can ask is: Why is there a nearly (162) universal genetic code when there are millions of possible ways to connect 64 triplet codons with 20 amino acids? To be precise: 1.5 x 10⁸⁴ possible codes (127, p.163). But all these possible code assignments assume 64 triplets of A,T,C,G and the same 20 amino acids. But why assume this?

  The genetic code

  1. Why only 4 bases while more than 100 nitrogenous bases are possbile? (160). Why are there 2 types of bases: purine and pyrimidine bases? Why not use 20 bases? (as many as amino acids) (111). The problem of prebiotic synthesis of the DNA bases is the same for independent origin and evolution, except that life did not start with DNA (but with RNA or something even more simple). However, the fact that the 4 bases in DNA are common to all life is only a problem for independent origin.
  2. Life universally uses the same 20 amino acids. Why only 20 amino acids while 150 amino acids are possible in nature? (160). Why exactly those 20 amino acids and not others? (the universal use of the same 20 amino acids points strongly to common descent of all life). Only 12 of the 20 amino acids can be synthesized prebiotically, the other 8 can only be synthesized by living organisms (208). So independently arisen genomes coding for 20 amino acids cannot function because 8 amino acids are missing.
  3. Why does the DNA backbone universally consist of deoxyribose and phosphate? And why does RNA use ribose instead of deoxyribose and Uracil instead of Thymine? The sugar deoxyribose is harder to make, and in present-day cells it is produced from ribose in a reaction catalyzed by a protein enzyme, suggesting that ribose predates deoxyribose in cells. (260). Alternatives for DNA are chemically possible (256). Senapathy a priori excludes any evolution from simpler bases and sugars to the current ones.
  4. Why 3 bases (triplet) as the unit of the genetic code? A code with only two bases and a codonlength of 4 or 5 is also possible (111).
  5. Why a commaless triplet code? (126)
  6. Why a non-overlapping code? (126)
  7. Why does the code has polarity? (code must be read in a fixed direction)
  8. Why are there precisely 3 stopcodons? Is it optimal? Why not 1, 2 or 4? (204) Why exactly those 3? Why is there a strong bias for stop codon usage in different eukaryotes? The non-random assignment of the 3 stopcodons (they start with U, and two start with UA) conflicts with the random origin theory.
  9. Why only one and nearly universal Start codon (AUG=MET)? A start codon is necessary because bases must be read in triplets and the correct base must be identified as the first of the triplet. The startcodon must hold throughout the whole genome. Misidentifying the first base of a triplet would result –if translated at all– in a different amino acid and consequently in a different protein (Just as in case of a one-base deletion or insertion).
  10. The degeneracy (redundancy) of the code is not random. The codons for an amino acid are clustered. This is the structure of the genetic code.
      Info: a redundant code is a logical consequence of 64 triplet-codons coding 20 amino acids and 3 stopcodons. So, on average an amino acid is coded by 3 codons, the real number varies from 1 - 6. Mostly, the codons for a particular amino acid have the same first two letters. The third letter varies most. This is not random! Furthermore:
  11. Why does the genetic code minimize the chemical consequences of amino acid mistakes? Optimal code, Steve Freeland (234).
  12. Neighbouring triplets in the genetic code tend to specify biochemically similar amino acids, so that single-nucleotide substitutions rarely lead to radical amino acid replacements (238). This is a non-random code!
  13. Why is there a codon usage bias? (see also: codon usage database). Some codons for the same amino acid are used very frequently, others rarely. Codon usage should be random in the independent origin scenario.
      Info: this is not about the structure of the genetic code, but about how often the codons are used in a genome. Statistically, one would expect that all codons occur in about the same frequency in DNA. This is not so. For example. there are differences in the frequency of occurrence of synonymous codons (139). For the amino acid LEU the most freqeuntly used codon is used 140 times more often than the least frequently used codon (33). In the bacterial kingdom the C+G percentage varies from 25% to 75% (35).
  14. Why is methionine the starting amino acid in the synthesis of most protein chains if DNA arose spontaneously? (Initiation Codons, eukaryotes)
  
  A lot of freedom of choice! If all these variations are chemically possible, why is there only one genetic code? Every Origin of Life theory has to explain this restriction, but:
  If organisms originated really independently, there should have been as many variations of the code as independently born organisms. (161)
  The reason is: each independent origin is a new trial. The probability is zero that in a few million trials (= the number of species) the outcome would always be the same result, considering the 1.5 x 10⁸⁴ possible genetic codes alone. And that is assuming 64 triplets of A,C,T,G and 20 amino acids. Let alone all the variations above. So, independent origin spectacularly fails.
  
  
  • Chemical necessity?
    The only possible escape would be that the genetic code would be a chemical necessity. In that case the same genetic code would be produced automatically again and again. Is the code a chemical necessity? Is seems now likely that only 25% of the codons can be explained by a chemical affinity of amino acid and codon-RNA, and 75% of the codons are arbitrary assigned (127, p.174). The 25% follows from the universal laws of chemistry and thus will be the expected outcome on any planet. However, 75% of the genetic code must be explained by common descent. That is an inherited and 'frozen' accident. Independent origin cannot explain universal arbitrary features of the genetic code because there cannot be millions and trillions of trials with exactly the same outcome! Unless one particular 'frozen accident' is inherited by all descendant species. This is called evolution by common descent and modification. Of course the theory of evolution needs to explain how the genetic code originated, but the fact that every species has the same genetic code can only explained by common descent. The frozen accident theory may be not the most elegant theory, but at least it is not ruled out by probability theory! Any talk about 'common pool of genes' destroys a truly independent origin of life. Conclusion: the universal genetic code is the strongest argument against independent origin I can think of (128).
    
    
  • Inheritance of the code
    Additionally, and crucially, despite being largely the result of an accident, the code is encoded in DNA itself. The encoding of a codon to its amino acid is a result of the aminoacyl tRNA synthetase which adds the aminoacyl group to its allocated tRNA. This embodies the connection between DNA triplets and amino acids (82). This fact alone destroys the random origin of a genome. The rest of this page constitutes additional evidence.
    
    
  • Evolution of the code

    "The important point to realize is that in spite of the genetic code being almost universal, the mechanism necessary to embody it is far too complex to have arisen in one blow. It must have evolved from something much simpler. Indeed, the major problem in understanding the origin of life is trying to guess what the simpler system might have been". Francis Crick (1981) Life Itself, p.71 (184).

    Is gradual evolution of the genetic code compatible with independent origin? Independent origin of complete eukaryotic genomes must assume the full set of 20 amino acids, because the current genetic code codes for 20 amino acids. Less than 20 will prevent the production of functional proteins. It cannot start with a subset of amino acids and later add additional ones (as in evolutionary scenario's). Evolutionary scenario's make the problem easier. For example, Wong proposed the evolution of the genetic code in two phases. In the first phase 6 - 10 amino acids were assigned to 61 codons. The code then expanded by the addition of phase-2 amino acids (145a). Any gradual evolution of the genetic code is incompatible with Senapathy's scenario. Not only the genetic code but also the genome would have to evolve. Both are (and must be) fixed in Senapathy's scenario. So, the burden to explain the abrupt origin of a full-blown 64/20 genetic code rests on Senapathy's shoulders. He did not address this difficulty (see also § 27: PLOS One article). See for other proposals of the evolution of the genetic code: (158).
    
    

  The Standard Genetic Code contains 18 fragile codons (red) that can be changed into a STOP codon by a single point-mutation and whose mistranscription can therefore generate nonsense errors. The remaining 43 sense codons are "robust" to such errors. Six amino acids are encoded exclusively by fragile codons ("fragile amino acids", shaded), ten amino acids are encoded exclusively by robust codons ("robust amino acids", unshaded) and four amino acids can be encoded either by robust or fragile codons ("facultative amino acids", hatched shading). We observe a 8% depletion of fragile codons in single-exon genes in the human genome that is highly significant. After Brian P. Cusack et al (240)

  
  
• A sequence constructed with any 4 'letters' is not DNA
  A sequence constructed with 4 different 'letters' is not DNA because the letters must be able to chemically pair specifically and reliably. They must consist of pairs. For example: A must pair with T, C with G. So not any 4 letters will do. A restriction applies which cannot be ignored. Furthermore, they must not only be able to pair, they must be able to separate temporarily for DNA replication. This pairing is completely absent from all computer simulations. Strangely, it seems irrelevant for computer simulations. But it cannot be ignored if one wants to solve the origin of life because DNA cannot exist without pairing. "All organisms, from bacteria to humans, face the daunting task of replicating, packaging and segregating up to two metres (about 6 × 10⁹ base pairs) of DNA when each cell divides." (Nature 28 Jan 2010). See: cell division (below).
  
  
• A single-stranded linear sequence of 4 letters is not DNA
  A sequence constructed with 4 different letters is not DNA because Prokaryotic and Eukaryotic DNA have a double stranded helix. Single-stranded DNA (ssDNA) viruses exist. Double-stranded DNA (dsDNA) creates a problem. In nature usually only one strand of a particular region in DNA (sense strand or coding strand) is translated into proteins. The other non-sense or antisense strand ('noncoding strand', 'complementary strand') is not translated. Senapathy's example in figure 1 is a virtual single-stranded DNA sequence. He ignores that both strand could be used as a code. In most organisms, the strand of DNA that serves as the coding template for one gene may be noncoding for other genes within the same chromosome (source). Amazingly, there are several protein coding genes encoded in the opposing strand of another gene! These are genes within genes. Example is the gene for neurofibromatosis type I (NF1) which contains 3 genes in the opposing strand of the intron (167). If genomes are random sequences, then Senapathy should predict that genes are located randomly on either strand. If there is an excess of genes on one strand, the hypothesis is falsified. The problem is that his approach is incapable to incorporate all these complications because he uses only single-stranded sequences.
  
  
• Double-stranded DNA does not form spontaneously 1 Feb 2012
  The spontaneous formation of double-stranded DNA has never been observed. Double-stranded DNA is always formed by semi-conservative replication on the basis of an pre-existing double-stranded DNA polymere (Meselson-Stahl, 1958). So, of each double-stranded DNA molecule one strand is inherited as it is from the mother DNA molecule and the other strand is newly synthesized.
  
  
• A linear sequence of A,T,C,G is not a gene
  A sequence of the bases A,T,C,G of arbitrary length is not a gene (or exon) because the length must be a multiple of 3. The reason: the code is a triplet code.
  
  
• A DNA sequence is not a chromosome
  

  "A DNA sequence isn't enough; to understand the workings of the genome, we must study chromosome structure. Far from being the random result of packing 2 metres of DNA into a sphere perhaps 10 micrometres across, the structures vary across cell types and exert an as-yet-mysterious influence on gene expression." (176).
  
  "We usually think of genomes abstractly as one-dimensional entities that are purely defined by their linear DNA sequences. Reality, of course, is far more complex. The DNA helix is folded hierarchically into several layers of higher-order structures that eventually form a chromosome" (177).

  telomeres (white dots), centromeres (red dots) (Science 22 April 2011)

  A random DNA sequence is not a chromosome because important chromosomal structures are present: telomeres, centromeres, nucleosomes, euchromatin and heterochromatin. At least these structures are present in linear chromosomes in eukaryotes, not in the circular chromosomes of most bacteria. Although linear chromosomes probably have advantages, they come with problems: replication of linear chromosomes presents a problem as it leads to gradual loss of the terminal telomeric regions, the telomeres.
  
  • Telomeres are needed to protect the ends of linear chromosomes and prevent their fusion. Without telomeres, the chromosomes would be shortened during each cell division, because DNA polymerase is unable to copy to the very end of one of the two DNA strands it is replicating. The protection conferred by telomeres is a fundamental biological mechanism present in nearly all animals and plants (119). With dysfunctional telomeres cells can no longer divide.
    
  • Centromeres are defined as pieces of non-coding repeated DNA with variabel DNA sequence that function as the site of spindle attachment at cell division (mitosis and meiosis). They are essential for equal chromosome separation during cell division. Remarkably, centromeres are inherited epigenetically. That means DNA sequence does not determine the identity of the centromere. This implies that ultimately the centromere is inherited from a previous generation. There is no previous generation in the Independent Birth of Organisms hypothesis.
    
  • Nucleosomes form the fundamental repeating units of eukaryotic chromatin, which is used to pack the large eukaryotic genomes into the nucleus while still ensuring appropriate access to it. Already in 1987 a publication appeared pointing out the relation between chromsome structure and gene expression.
    "Since 1968, we have learned that DNA wraps around histones, packing ~10² base pairs into the 10^–8m nucleosome. We also know that individual chromosomes occupy distinct subnuclear volumes called chromosome territories which pack ~10⁸ base pairs into 10^–6 m (243). Where do histones come from in the independent origin scenario? It does not help that they are encoded in the DNA, because how are they supposed to be transcribed into mRNA and translated into protein?
    
    

    ©Science 2 Dec 2011

  • Linear chromosome: Here is the fundamental problem for the theory of independent origin: why should the most complex chromosome type, the linear chromosome, with all its problems, arise spontaneously in stead of the circular chromosome? For example: why don't humans have 46 circular chromosomes? Or why don't humans have one big circular or non-circular chromosome? On the other hand, evolution theory needs to explain the evolution of the linear chromosome (120).
• DNA requires a DNA synthesizer
  Even if we assume statistics allows for a complete eukaryotic genome in a random sequence of A,T,C,G, then still those DNA sequences must be synthesized from chemical building blocks: bases, deoxyribose, phosphate. It turns out that this is extremely difficult abiotically (83). Enzymes are required: Deoxyribose is generated from ribose 5-phosphate by ribonucleotide reductases. Nucleotides, the building blocks of DNA have never been produced in any prebiotic synthesis experiment. The enzyme dihydrofolate reductase is required for making nucleotides. At the same time enzym inhibitors prevent DNA synthesis. This is fatal for de novo DNA synthesis. (Mainstream science has the RNA-world and the Pre-RNA world).

• A DNA sequence is nothing without proteins: histones, DNA polymerases, RNA polymerases, telomerases, topoisomerases, helicases, ligases, release factors, nuclear receptors, histone demethylases, DNA repair enzymes, transcription factor, repressor, activator, spliceosomes, splicing regulatory proteins, nucleases, DNA methyltransferase enzymes, ribosome.
  Here is the paradox in a nutshell: to produce a protein from DNA specific proteins are needed. It does not help that those proteins are encoded in DNA. Surely, every necessary protein could be encoded in random DNA. The point is that it needs to be transcribed and translated (250). That requires enzymes to be present in the first place. The central dogma of molecular biology states that genetic information encoded in DNA is transcribed to mRNA by RNA polymerases, and mRNA is translated to protein by ribosomes. Since RNA-polymerase is a protein itself, it needs to be present before it can be produced. This is certainly impossible for the first 'independent organism'. This alone is fatal for independent origin. This is why the origin of any organism from pure DNA is impossible! This is why scientists concluded that there must have been a RNA-world before a DNA-protein world.
  Three examples:
  
  1. Transcription:
     There are more than 1000 transcriptional activator proteins encode in the human genome. Even in the simplest well-studied eukaryotes (yeast) there are perhaps 200 activators (228). 11 Oct 11
  2. Translation:
     "Translation is probably the most complex biochemical cellular process, needing more than 120 different molecular elements ranging from messenger RNA to ribosomes and their many protein and RNA accessories. According to Fraser and coworkers, even the smallest of cellular organisms (Mycoplasma genitalium) need a minimum of 90 different proteins for translation and about 30 for DNA replication." (185), (250). The eukaryotic ribosome is composed of 79 ribosomal proteins.
  3. Replication:
     DNA polymerases are a family of enzymes that carry out all forms of DNA replication. Human DNA polymerases are 900-1000 amino acids long (2700 - 3000 base pairs). Eukaryotes have at least 15 DNA Polymerases. "The work of a generation of biochemists, notably Arthur Kornberg, has shown that it takes dozens of protein complexes, each involving many proteins to accomplish this. [replication] They can be thought of as complex components of several giant molecular machines, which synthesize the new DNA, check it for errors, and pass it on for further interactions which package it in chromosomes." (264).

• DNA specifies amino acids but does not synthesize amino acids 1 Feb 12
  DNA specifies the sequence of amino acids in proteins but does not synthesize amino acids. So, when there are no amino acids available (for example essential amino acids), protein synthesis is impossible. To synthesize 'non-essential' amino acids the cell needs specific enzymes. Those enzymes can only be produced when the right amino acids are available. This is because enzymes are a sequence of amino acids.
  
  
• DNA sequence is not sufficient to produce proteins 13 Jul 11
  About one quarter to one third of all proteins require metals to carry out their functions (metalloproteins: iron, copper, magnesium, cobalt, zinc, molybdenum, vanadium, manganese, nickel, selenium). For example, iron and copper are present in virtualy all enzymes and in some proteins that interact with oxygen (215). However, metals are not coded by DNA! So, protein specification by DNA is incomplete. Furthermore, most of the Mg2+ in a cell is bound to DNA, to RNA, to the cellular energy carrier ATP or to enzymes, and acts as an essential cofactor for these molecules. Mg2+ is not in the Sequence.
  
  
• DNA synthesis requires energy
  "Each building block needs to be activated, or chemically charged, before it can be incorporated into a polymer. Activation requires a preexisting source of chemical energy." (256). "It has been known for nearly 20 years that chromatin assembly is an ATP-dependent process" (146). There are two energetic components: the costs of nucleotide synthesis and the polymerization cost needed to make a DNA or mRNA molecule (188).
  
  
• Why a DNA genome? 24 Jun 11
  Why are the first genomes made of DNA? What's wrong with RNA genomes? Double-stranded RNA viruses do exist. If DNA is necessary for genomes, why does life use RNA at all? Where does RNA come form in the independent origin scenario? RNA is indispensable anyway.

• The Transcription Code 18 Feb 11
  The genetic code is not the only code. The processing of the information of DNA starts with transcription, which requires:
  • each gene has its own promoter element (contains a conserved gene sequence called the TATA box) and enhancer element(s)
  • initiation codon: AUG is an initiation codon or start codon. The next gene does not start right after the stopcodon, so an initiation codon is needed. Senapathy ignores this.
  • termination codon UAA that stops transcription.
  Where does the Transcription Code come from? It is not random.

• The Histone Code 4 Oct 2011
  The histone code is a hypothesis that the transcription of genetic information encoded in DNA is in part regulated by chemical modifications to histone proteins, primarily on their unstructured ends. Together with similar modifications such as DNA methylation it is part of the epigenetic code. (see Epigenetics below)

• The Splicing Code 18 Feb 11, 9 Mar 11
  The very existence of introns requires splice site recognition: the border between intron and exon. So, Senapathy simply assumes splicing machinery when talking about introns and exons. This is the splicing code. Where does it come from? How is it done? Why that specific code? Why the universal splicing code? The splicing sequence is in DNA, but that is only 'a code' if specific proteins (splicing regulatory proteins) recognize that sequence. So, it does not solve the problem of the origin of split genes to search for splicing codes in random DNA. Of course one will find it in random DNA. The point is, however, that the splicing code is not random, so where does it come from? The spliceosome is a very complex ensemble of five snRNAs and about 200 proteins, so cannot arise from scratch. Furthermore, alternative splicing implies different proteins in different cell types. In addition to splicing, eukaryotes possess elaborate mRNA surveillance mechanisms, in particular nonsense-mediated decay (NMD), to assure that only correctly processed mature mRNAs are translated (170). This effectively blocks the origin of splicing from scratch.

• The Poly(A) Code 18 Feb 11
  The information in DNA is modified before it is used. No equivalent to poly(A) or the caps are in DNA and these are added to the mRNA (Polyadenylation). Therefore, a DNA sequence is not enough. The mRNA is modified. This is crucial for exporting mRNA from the nucleus to the cytoplasm. Alternative polyadenylation can also shorten the coding region, thus making the mRNA code for a different protein. Again: the information in DNA is not enough.

• A DNA sequence does not survive
  

  "Any theory postulating that genes [!] may have emerged randomly and then waited to be used are fundamentally wrong, especially in a world dominated by the deleterious effects of the second law of thermodynamics. Genes had to have a functional meaning from the very beginning or they would have vanished soon after they emerged." (53).

  Please note, this applies to genes. Let alone to genomes. Furthermore, phenotypic effects of DNA are ignored: RNA-editing changes the sequence, and so the phenotypic effect. With no RNA-editing in the primary pond, the DNA sequence would probably not survive for this reason alone.

• A genome is not an arbitrary collection of genes
  Even if all eukaryotic genes are produced abiotically, on statistical grounds it can be excluded that random assembly of genes will produce an eukaryotic genome. We even haven't yet a good understanding of which genes are important and what their contribution to the whole genome is. (See problems with Genome Wide Association Studies).

• Epigenetics: a sequence of 4 bases is not enough to produce an organism.

  "The major problem, I think, is chromatin. What determines whether a given piece of DNA along the chromosome is functioning, since it's covered with the histones? What is happening at the level of methylation and epigenetics? You can inherit something beyond the DNA sequence. That's where the real excitement of genetics is now." (James D. Watson: 30).

  A genome is more than a sequence of 4 bases. A complete DNA-methylation map of the human genome is required. Methylated cytosine, often referred to as DNA's fifth base, makes up a subset of nucleotides in the mammalian genome (121). It can regulate tissue-specific gene transcription, without affecting the genetic blueprint. Cytosine methylation may function as a memory module of cell identity and developmental state.
  Two epigenetics examples:
  1. Two studies of mouse embryogenesis now show that transmission of DNA methylation from gametes is predominantly maternal. Mouse embryos need maternal imprints for normal development.
  2. FBHM (Familial biparental hydatidiform mole) is a recessive disorder that results in repeated pregnancy loss due to a failure to establish maternal imprints at multiple loci throughout the genome (227).
     
  Chromatin is defined as the dynamic complex of DNA and histone proteins that makes up chromosomes. Epigenetics is defined as the chemical modification of DNA that affects gene expression but does not involve changes to the underlying DNA sequence. As the emphasis in biology is switching away from genetic sequence and towards the mechanisms by which gene activity is controlled, epigenetics is becoming increasingly popular (104).

  ©Nature

  Epigenetic processes are essential for packaging and interpreting the genome, are fundamental to normal development and are increasingly recognized as being involved in human disease. Epigenetic mechanisms include, among other things, histone modification, positioning of histone variants, nucleosome remodelling, DNA methylation, small and non-coding RNAs. (Nature, 7 Aug 2008).

• 12 Feb 2011 A DNA sequence is nothing without a nucleus
  The defining property that sets eu-karyotic cells apart from pro-karyotic cells is the nucleus (wiki).
  "Genomes are more than linear sequences. We usually think of genomes abstractly as one-dimensional entities that are purely defined by their linear DNA sequences. In addition to the complex arrangement of the genetic information itself, the cellular factors that read, copy, and maintain the genome are organized in sophisticated patterns within the cell nucleus. Specific nuclear processes such as transcription and replication occur at spatially defined locations in the nucleus." (177), (178).

• A DNA sequence is nothing without a cell
  Remarkably, in the Appendix Senapathy knows:

  "Unsually, an organism starts its growth from a single cell" (p. 536)

  He seems to forget this important fact in his theory. A sequence of DNA is useless without a cell: membrane, mitochondria, ribosomes, nucleus, nuclear membrane, centrosome. (See further details: par 7 Genome-centered approach).
  • Cell division (mitosis): from the first animal or plant genome a body must be created. That means millions of cell divisions. Chromosomes do not only create an organism, they are duplicated just before each cell division. "Chromosome segregation must be executed with high fidelity so that the mother cell and the daughter cell that arise from division receive precisely the same DNA content". Otherwise aneuploidy will result. Comparing the length of metaphase chromosomes to that of naked DNA, the packing ratio of DNA in metaphase chromosomes is approximately 10,000:1 (Nature). Therefore, central to the problem of segregation is the issue of packaging." (Nature). Mitosis is a complicated process in which about 625 genes are involved (Nature). The spindle apparatus is the structure that separates the chromosomes into the daughter cells during cell division. Without spindle no cell division. The kinetochore is a complex machinery composed of more than 100 proteins through which chromosomes attach to the microtubules that form the spindle apparatus, which allows chromosome segregation. (see above: 'A DNA sequence is nothing without proteins').
  • Cell division and multicellularity: A human develops from a single cell. From that single cell, an individual grows to 10¹³ to 10¹⁴ cells. Each time a cell divides, the number of cells in the body increases by one, assuming no cell death. So, to start with one cell and expand to 10¹³ cells requires at least 10¹³ – 1 cell divisions (225). Prokayotes do not have this problem, because they are single-celled.
  • Synthetic genomes. Lessons from synthetic genomes: the first synthetic genome (a bacterial genome) was created from scratch in the lab by Craig Venter in May 2010.
    1. The first lesson: this work didn't create a truly synthetic life form, because the genome was put into an existing cell (129). (the original genome was carefully removed before it received the new genome).
    2. The second lesson: it is very difficult to create a 1-million-base genome. Blue Heron (The Gene Synthesis Company) has mastered the art of synthesizing relatively long, entirely accurate sequences, and stringing them together to create gene-sized fragments on the order of hundreds to thousands of bases. However, the human genome is 3000 times bigger! To assemble a one million genome from 1k pieces the process involved, according to Venter, "invention after invention after invention of new ways to do things" and "There were literally thousands of hurdles that had to be overcome" (201).
    3. The third lesson: errors! Initially the attempt failed because the artificial genome failed to take control of the cell. The cause was a single-base mistake which delayed the project 3 months (129).
• A DNA sequence is nothing without an organism: parts of the DNA sequence (genes) must be expressed at the right time and place in the right quantities in order to develop an adult from one cell and maintain life als an adult. To achieve this, proteins that control such processes have to bind to specific places in the genome. There is evidence that ageing entails a gradual drift towards more random patterns of gene expression, which might cause organ/tissue failure. There are millions of ways to express genes at the wrong time, place, quantity or sex. Furthermore:
  • other genes in the genome influence the function of a gene
  • the function of the gene product must be in accord with the laws of biochemistry (energy production, protein folding, catalysis, prevention of protein aggregation). Some proteins cannot fold without the help of other proteins, called chaperones, so that means: genes cannot function in isolation, they need other genes.
  • DNA must be protected from damage: right from the start DNA must be protected from damage (mutation). Indeed: a very complicated DNA-repair system exists. Furthermore, DNA must be faithfully duplicated (replication) with the help of specialised enzymes. It is highly improbable that they arose by chance.
  • a sequence of DNA is meaningless without the correct ecological context, that is biological and nonbiological (the physical conditions of the earth: temperature, atmosphere, climate, gravity, water). See: The genome is blind.

• A DNA sequence is not an organism: an eukaryotic organism contains multiple separate genomes. See: separate page. Explaining the nuclear genome is not enough.

• A computer generated DNA string is a virtual thing. See: here § 6.

• The limits of a Genome-centered approach: § 7

1. origin of DNA: a chemical problem
2. origin of genomes: a biological problem
3. origin of information: a mathematical problem (statistics)

A test for randomness

1. A test for randomness

   If DNA has directly arisen from random assembly of the building blocks and genomes are immutable, then all genomes we examine should show randomness. Every bit of processing or selection destroys the random nature of genomes. A prediction is that the distribution of stopcodons should be random. Is it? Actually there are two questions: What do we observe? What do we expect? Senapathy does not state this clearly at the beginning. Senapathy produces plots to answer both questions, but they are difficult to read, not well explained and do not seem to support his theory. A stopcodon is the DNA code for the end of the protein. If the distribution of stopcodons in current genomes would match a purely random distribution, it would be strongly suggestive for the random origin of genomes. The frequency of stopcodons in a random computer generated DNA string must be calculated on the basis of the fact that 3 out of the 64 codons are stopcodons (4.7%) (assuming this holds for the origin of life also). So I would expect 47 stopcodons in 1000 codons (=3000 bases). Assuming all codons have equal probability, the average length of genes between two stopcodons would be 1000/47=21 codons (=63 bases) (my calculation, Senapathy does not show this). However, this is too small for a gene! Genes are hundreds or thousands bases long. According to Senapathy the expected length of genes in computer generated random sequences would vary from 0 (two stopcodons next to each other!) up to 500 or 600 bases, but "More than 95% of all random genes are shorter than 100 bases" (p.234).
   According to Senapathy genes in organisms are often 9000 bases (=3000 amino acids) long (p234). So this is far above the length of the genes found in the computer generated sequences. Therefore, I would conclude that typical eukaryotic genes could not be formed directly from randomly assembled DNA. Nevertheless, Senapathy does not seem to be discouraged by this result. He invokes a kind of processing of DNA that results in eliminating all the shorter DNA sequences and leaving all the longer sequences. This processing has to result in two things: eliminating pieces with too many stopcodons and producing precisely the genes we find today. However, these 2 goals do not automatically cooperate. Worse, there is no connection.
   The problem with this idea is that right from the start in his procedure he makes unwarranted assumptions, such as that the key sequences necessary for proper splicing are just there! One must not only find exons! This is not shown in the above computer simulation! So we should not search for: TO BE OR NOT TO BE, but something like:

   XYZTOXYZ   XYZBEXYZ   XYZORXYZ   XYZNOTXYZ   XYZTOXYZ   XYZBEXYZ

   (XYZ being splicing recognition sites). How else can the words (exons) TO BE OR NOT BE be recognised? (26) In reality the number of bases that are essential for proper splicing is unlikely to be less than 10 and is plausibly as high as 30 (39). To be correctly processed to proteins, begin and end of exons need to be recognised. However, this would make the task of finding them in a random sequence far more difficult than Senapathy imagined.
   I see another problem with his data: he shows graphics showing that the shortest DNA sequences (down to zero length) are most frequent! Why is this? He does not explain. Why is there not a normal distribution around the mean length?
       Further questions: Senapathy does not tell us why there are only 3 stopcodons and not 1 or 2 or not more than 3. If only 1 stopcodon existed, that would produce much longer sequences. Maybe there used to be only 1 stopcodon at the origin of life and later 2 were added. So Senapathy's assumption is unsubstantiated, and he could have used speculatively 1 stopcodon: 1,56% stopcodons = 156 stopcodons in 10.000 codons (=30.000 bases) = mean length = 64 codons = 192 bases (still too short).
       A further question: (25 Sep 2011) why does Senapathy ignore Startcodons in his calculations? Genes require startcodons. Genes are not defined by stopcodons alone. A gene requires a startcodon and a stopcodon. This has a profound effect on the simulations.

2. Codon usage bias

   The genetic code is redundant. The number of codons for amino acids varies from 1 - 6. However, the usage of synonymous codons is non random. Some are rarely used, others with high frequency. For the amino acid LEU the most freqeuntly used codon is used 140 times more often than the least frequently used codon (33). This is a genome wide bias. There should be no such huge codon bias when genomes arose by chance from the primordial pond. In the independent birth scenario all codons for a amino acid are expected to occur on average with the same frequency.

3. Dinucleotide frequency

   Since the genome of any organism arose randomly, each genome must have identical statistical properties. How could they differ significantly? A departure from randomness refutes the random origin hypothesis. For example, within the human genome each of the 4x4=16 possible dinucleotides should be present in equal frequency (6.25%). However, there is a notable depressed level of the CG dinucleotide (0.99% compared with 9.80% of TT dinucleotde). (Stewart Scherer (2008) A Short Guide to the Human Genome, p. 11.)

4. Mononucleotide repeats 18 Nov 11

   Are nucleotide sequences actually used by organisms a random sample of all the possible sequences encoding that particular amino acid sequence, or do they deviate from a random choice? Short mononucleotide repeats occur at about the frequency expected by chance, but longer mononucleotide repeats are substantially rarer than predicted by the null model in all three organisms C. elegans, S. cerevisiae, and E. coli. For example, in E. coli, the codon TTT is avoided in favor of TTC at positions immediately followed by a T. This reduces the frequency of runs of four Thymines, and thus indirectly also of longer stretches of Thymine that necessarily contain runs of four. (237). Explanation: as mononucleotide repeats are prone to slippage during transcription and translation, the most parsimonious explanation is selection against error-prone nucleotide composition.

5. Chargaff's cluster rule

   Apart from the first parity rule (A=T C=G), Erwin Chargaff made three other fundamental observations on the base composition of DNA, which are only now being incorporated into mainstream biology. The first species-invariant observation was that individual bases are clustered to a greater extent than expected on a random basis (197) which contradicts random origin.

   "Another consequence of our studies on deoxyribonucleic acids of animal and plant origin is the conclusion that at least 60% of the pyrimidines occur as oligonucleotide tracts [runs] containing three or more pyrimidines in a row; and a corresponding statement must, owing to the equality relationship [between the two strands], apply also to the purines." (197)

6. Chargaff's second parity rule

   The second species-invariant observation was that Chargaff's first parity rule also applies, to a close approximation, to single-stranded DNA. The validity of the rule became clearer when full genome sequences became available. For example, the "top" strand of Vaccinia virus has 63921 A, 63776 T, 32010 C, 32030 G (197). The bacterium Sarcina lutea has an extreme (A+T)/(G+C) ratio of 0.35 (Biopolymer Chemistry). If DNA were random 25% A, 25% T, 25% C, 25% G are predicted. So, again random origin is refuted.

7. Chargaff's GC rule

   The ratio of C + G to the total bases (A+C+G+T) (CG-content) tends to be constant in a particular species, but varies between species (197). The CG-content or AT/CG ratio of genomes is not 1:1. Already in 1952 CG percentages as low as 34,8% have been discovered in the DNA of insect viruses (34). In the bacterial kingdom the CG percentage varies from 25% to 75% (35). Acidianus infernus and Methanococcus jannaschii have 31% GC-content (255). A species with an extremely low GC-content is Plasmodium falciparum: ~20% (wikipedia). Although some deviation from the mean of 50% is to be expected in a random sequence of DNA, extreme deviations are highly improbable and contradict random origin.

8. A test for randomness of phase 0,1,2 introns 16 Mar 11

   An intron could start between or within triplet codons. The same is true for the end of an intron. Between codons is called (phase 0), within codons is called phase 1 (after the first base) or phase 2 (after the second base). If introns have the same phase at the beginning and end, they are symmetric, otherwise they are asymmetric. There are three symmetric intron types (0,0), (1,1), and (2,2) and six asymmetric types (0,1), (0,2), (1,2), (1,0), (2,0), and (2,1). The theory of random origin of introns and exons predicts that all 9 intron phases should have approximately the same frequency in random DNA. Already in 1992 Fedorov et al. showed that the proportions of the three intron phases were significantly unequal. In 1993 Green et al. showed excess phase 0 introns and excess symmetric exons in ancient conserved regions (ACRs). Later publications based on GenBank give the same results. The proportions of three intron phases and frequencies of nine associations of introns showed significant nonrandom distribution: 48% phase 0, 28% phase 1, and 24% phase 2 and all symmetric exons (0,0), (1,1), and (2,2) showed significant excess over a random prediction (199). Conclusion: random origin is refuted.

9. A test for randomness of proteins

   Ptitsyn (136) concludes "that primary structures of proteins are basically just the examples of random amino acid sequences which have only been 'edited' during biological evolution". Pande et al (137) examine the possible random nature of protein sequences. The hypothesis was that proteins are slightly edited random sequences. They found pronounced deviations from pure randomness. Keefe & Szostak (138) state that "Functional primordial proteins presumably originated from random sequences". However, even if proteins emerge spontaneously prebiologically, this is irrelevant for the origin of life, because proteins cannot be translated in to DNA (Crick's central dogma of molecular biology). So, the result is useless for the question of random origin of DNA. Douglas L. Theobald (130) wrote "Many proteins probably do exist that have independent origins. For instance, in the Metazoa certain protein domains have probably evolved de novo that are not found in either Bacteria or Archaea. However, the independent evolution of unique Metazoan proteins, by itself, is not evidence for or against UCA." (UCA= Universal common ancestry).

10. Non-random genome architecture
    Are genomes randomly arranged assemblages of genes or is gene order non-random? Genome architecture (that is, the order, spacing and orientation of genes in the genome) can be highly non-random (239).

11. Paul Davies about genomes

    "If genomes are information-rich, then they have to be random (or almost so). If biological organization is random, its genesis should be easy. [!] The vast majority of possible sequences in a nucleic-acid molecule are random sequences. Only a tiny, tiny fraction of all possible random sequences would be even remotely biologically functional. A functioning genome is a random sequence, but it is not just any random sequence. It belongs to a very, very special subset of random sequences" (40)

    So Senapathy is right about genomes being mathematical random, but its production is not easy because only a tiny, tiny fraction of the genomes are functional. Without knowing it, Davies refuted Senapathy.

The genome-centered and information-centered approach

"Thus, the genome is the master of the cell and the organism."     (p.551, Appendix - Genetics Primer)

The pervasive effect of the discovery by Watson and Crick of the α-helix structure of DNA and the Central Dogma is the genome-centered view of life. However, DNA only codes for protein. DNA does not create carbohydrates, fatty compounds, energy, nutrients. Energy and nutrients are external to DNA and the cell. DNA may encode a cell's potential, but the RNA molecules present dictate the activities that define a cell's state at any particular moment (252). Introns and splicing are central to Senapathy's theory. Splicing occurs at the level of RNA, not DNA. Senapathy's approach is genome-centered and information-centered. Life is first reduced to genomes and then DNA is reduced to information which a computer can handle. The Central Dogma is indeed central to biology, but that by no means does imply that it was involved in the origin of life. DNA does not produce Life. A related problem is genetic determinism. Niche-construction theorists, like developmental biologists, view phenotypes (and hence their environmental modification) as underdetermined by genes (247). A phenotype cannot be predicted from a genotype.

A quick glance at the internal structure of a cell is enough to see the limitations of the genome-centered approach:

According to wikipedia

According to Senapathy, p.552 Please note: except mitochondria, there are no internal structures in the cell and no indication of DNA in mitochondria. See: Endosymbiosis theory refutes Senapathy, and: section 28.

Senapathy has a gene- and genome-centered approach to explaining life. Probably, that was the common wisdom in 1994 when he wrote his book. Indeed, genes determine most of the differences between humans and other species. But Senapathy does not know its limitations when explaining the origin of life. The big mistake is to believe a naked genome is technically capable of creating a human being. This is succinctly described by the historian Jan Sapp:

"Critics of gene theory continue to emphasize that only a cell can make a cell, and that plant and animals emerge from eggs, not genes" (38)

"strange claim by some of the world's leading molecular biologists that the human genome is the holy grail of biology is a stunning example of a biology that has no genuine guiding vision"

Cell membrane

"One of the main arguments I will make in this book is that structures resembling microscopic soap bubbles were an absolute requirement for life to begin, as essential to the process as the assembly of genes and proteins". (David Deamer (2011) 215, p.3.)

A DNA sequence is meaningless "A DNA sequence, by itself, is meaningless. The information in the double helix is interpreted through its interactions with the rest of the cell." Barton et al (2007), EVOLUTION, p.381.

A DNA sequence is an archive "An organism is not a linear script in a DNA language we have learned to read. In fact, such a simplification is a shocking distance form the truth." "Without RNA, a cell would be all archive and no action". Michael Yarus (2010) Life from an RNA World, Harvard University Press, p. 97.

A DNA sequence is dead "Despite its obvious importance to life, biological energy receives far less attention than it deserves. According to molecular biologists, life is all about information. (...) Life without energy is dead" Nick Lane (2005) Power, Sex, Suicide, p.68.

DNA is an inert database "DNA isn't life. It doesn't even leave the nucleus of the cell. A whole army of proteins is needed to unpack, edit, and execute the information it contains. Without this apparatus, DNA is but an inert database, full of errors and repetitions. To grasp the nature of life, we must move away from our obsession with genes alone." front flap text of Denis Noble (2006) The Music of Life. Biology Beyond the Genome (216)

DNA does not 'play itself' Does this sheet music play itself? Of course not. Sheet music is coded music, but it needs an interpreter to become music. Even a pianola roll does not play itself! You need a pianola to play the music encoded in the paper roll. A pianola roll without pianola is dead. Also, DNA does not 'play itself'. It needs cell machinery to 'play itself'. DNA without a cell is dead. Would a paper roll with random holes encode 'random music'? That is certainly possible, but still a pianola is required to play it. And the pianola itself does not spontaneoulsy arise out of random parts.

The logic of the genome-centered view

Why would the primordial pond not produce independent nerve cells, muscle cells, kidney cells, brain cells, heart cells which combine randomly into organisms? Why would the primordial pond produce multicellular organisms by means of single cells developing into multicellular organisms? Why would a genome-centered theory predispose to our well-known embryological developing programme?

Information centered approach

This is what I wrote in a review years ago: "Information is the ultimate explanation of life. Information is the secret of life. This view of life is an oversimplification" (202). Senapathy is victim of this oversimplification because he thinks a computer simulation of statistical properties of DNA is enough to explain the origin of life (eukaryotes). However, Senpathy is not the only one. Famous ultra-Darwinist Richard Dawkins described organisms as information carriers based on the idea that bodies are containers for DNA, which itself is just a code and storage format from an informational point of view.
Another aspect of the information and DNA centered view is the fact that DNA contains the information that is faithfully transcribed and translated into proteins. This view is wrong. One of the main reasons is RNA-editing, which means the non-random replacement of one base by another (for example A-to-G or C-to-T) and ends up in the protein sequence (214). This means that the DNA sequence is not sufficient for producing proteins. Furthermore, RNA-editing does not make sense if the information of DNA originated from random DNA sequences. If the endproduct of RNA-editing is useful for the organism, why would DNA sequences representing the protein sequence not be selected in the first place? That would be the more likely event.
Furthermore, Senapathy ignores DNA methylation which adds extra information to the primary DNA sequence (epigenetics) and it controls transcription factor binding sites and regulatory regions.

Conclusion:
Shortcomings of the DNA-centered approach are: it ignores cell and cell membrane, cell arises from fertilization, and genes need to be regulated and true understanding of gene regulation requires the study of epigenetics and a lot more. Furthermore, RNA-editing changes the information transcribed from DNA. Therefore, any DNA-centered theory of the origin of life is incomplete and wrong. Certainly, if eukaryotic life is claimed to be the first form of life.
Even within the genome-centered view two different views are possible: 'the regulatory code' versus 'the protein code'. Senapathy exclusively pays attention to protein-coding sequences (exons). However, many of the observed differences between species likely stem from when and where the products of the genes are made, in other words: 'the regulatory code'.

I collected additional technical reasons from developmental biology, genetics and ecology on the page: Independent Origin and the facts of life.

Everything you always wanted to know about s e x, but were afraid to ask

1. Human body cells are diploid: one complete set of chromosomes from the father, plus one complete set from the mother. (95)
2. sperm and egg cells are haploid: 1 incomplete set of chromosomes.
3. a zygote is a fertilized egg: haploid egg + haploid sperm = diploid zygote.
4. humans have a diploid set of 23 pairs or 46 chromosomes in total
5. females have 23 identical pairs, including a X-chromosome pair, excluding the Y-chromosome
6. males have 22 identical pairs and one non-identical pair of a X-chromosome and a Y-chromosome. The Y-chromosome is about 1/5 the size of an X-chromosome (see photograph, and diagram: Fig. 2).
7. Egg cells have always one X chromosome and sperm cells have either one X or one Y chromosome.
8. additionally female egg cells contain many mitochondria each containing 37 genes. The mitochondria are transmitted exclusively via the female egg cell.
9. The number of genes in the human genome is about 22,000 genes (estimates vary, but that is not relevant for my argument).

So far the facts of life. Now Senapathy's claims that

"The genomes were directly assembled into single seed cells, analogous to the fertilized eggs of sexually reproducing organisms" (p.5) "male and female 'seed cells' lead to male and female individuals"; "Both male and female seed cells can be assembled"; "One can infer that it is not difficult to segregate the genes for a male or a female into a specific chromosome and in two different sex cells". (p.358)

"Perhaps among the organisms produced in the primordial pond, some had only secondary sex organs, but no genital organ to copulate; whereas other organisms would have the latter but not the former. Both the above situations may or may not have had the reproductive cycles of sperm/egg production. There could have been many seed cells producing individuals, with wrong combinations of male and female sex organs and secondary sex characteristics. Rarely, some seed cells will process all the three sets of genes for all these three functions - attractiveness by secondary sex features, copulation by genital organs, and reproduction by sperm/egg cycles. This is analogous to many seed cells giving rise to individuals with improper or incomplete organs, which will not survive. Only those individuals with the absolutely right organs will survive. Therefore, only one out of myriads of seed cells may form a viable organism. This may explain why it would have taken geological time for seed cells to be formed with genomes capable of producing viable organisms." (page 358-359.) (my emphasis) (97)

Can a male or female arise from haploid cells?

X     Y Fig 2. Human sex chromosomes (2)

      Degenarate polyploid genomes  

The situation is even worse. Many plant species are polyploid, having duplicated genomes. For example: yeast Saccharomyces cerevisiaea is a tetraploid and its genome consists of four roughly identical genomes (the diploid number is 4N). Because of the accumulation of mutations during the history of the species the original identical genomes start to differ. These are called degenerate tetraploids. Is is highly unlikely that degenerate tetraploids originated spontaneously from a pool of random DNA segments (especially all mutations being neutral).

      Virgin birth?  

Male bees, wasps, and ants develop from unfertilized haploid eggs, so are haploid. Would that help Senapathy's theory? No, because a diploid female has to produce the egg. Although it is known for an egg to start developing without being fertilised (parthenogenesis) in some insects, snakes (boa constrictor), lizards, and Komodo dragons, and parthenogenesis has been reported in about 70 vertebrate species (roughly 0.1%) and even in sharks (75), but not in mammals. Early mammalian development has a strict requirement for genetic contributions from a male and a female parent (174) and fully parthenogenetic human embryos cannot develop to term (4). The embryos die after a few days. Maternal and paternal genomes are both necessary for normal development in mice, and this is believed to account for the absence of parthenogenesis [=development without fertilisation by a father] in mammals (31). An embryo that did not have a sperm involved in its formation cannot make a placenta (the organ that keeps the fetus alive) and so cannot be born (54).
In plants the formation of asexual seeds is called apomixis and it leads to populations that are genetically uniform maternal clones (apomixis is found in more than 400 species of flowering plants). Even if parthenogenesis would work in humans, this only produces females, so would not explain the origin of males. This does apply to all animal species with an XX-female/XY-male sex-chromosome system. There is no Y-chromosome in a female cell, therefore a male cannot be produced parthenogenetically.
    Apart from the Y-chromosome, all sexually reproducing animals, simply have two parents. Asexually reproducing species (making clones of themselves) like bacteria, only have one parent.

      Conclusion  

Senapathy's computer experiment shows a single sequence (Fig 1). The analogy with a haploid genome is obvious. I guess he based his theory of independent birth on the idea of a haploid genome and assumed it was no problem to produce diploid organisms. Regrettably, the haploid method fails to produce the first human male and female. The haploid method can only produce asexually reproducing bacteria and other prokayotes. The funny thing is that Senapathy knows about X and Y chromosomes when he wants to refute neo-Darwinism, but does not realise that they are an insurmountable obstacle for his own theory. Nobody would deny that simple genomes have a higher probability than complex genomes. Therefore, a haploid organism should be the expected outcome of the primordial pond. Multicellular haploid organisms do exist: males of the honeybee are haploid. Senapathy is confronted with the amazing but inevitable question: why on earth are not all species haploid?

The above problem points to a wider problem: Senapathy does not distinguish between the origin of an individual and a species. How to proceed from the first individual to a population of interbreeding individuals? (Note: Only a few genes can prevent interbreeding of individuals of the same species (incompatibility genes, hybrid sterility, reproductive isolation). Self-incompatibility is of special importance because of obligate outcrossing. Self-pollination in plants requires only one individual, but still is sexual reproduction and few plants actually self pollinate.

Can a male or female arise from diploid cells?

        two kinds of cells - two kinds of cell division  

Could the first organism be a hermaphrodite? In a hermaphrodite species all individuals have both male and female reproductive organs. The possible advantage would be that there is no need to produce two individuals (males and females) which differ in the DNA that determines sexual characteristics, but have otherwise equal genomes. Therefore, the origin of the hermaphrodite species could start with just one self-reproducing individual (snails, plants). Apart from all other objections, if successful, it would only explain hermaphrodite species, not the majority of species with males and females. Furthermore, it would not even explain all hermaphroditic species: many flowering plant species are obligate outcrossers that cannot self-fertilize because of self-incompatibility: they recognize and reject their own pollen.

      A male without a Y chromosome?  

Males of grasshoppers and aphids ('plant bugs') do not have a Y chromosome, they are described as XO. Females of those species have two X-chromosomes; they are XX (36). Are females of grasshoppers and aphids perhaps candidates for independent origin? Theoretically they could produce a species. However, apart from the absence of the Y-chromosome problem, the problem of producing a female and male version of the same genome still exists. Furthermore, the production of males requires a rather unusual form of meiosis. Apart from this, if successful, it would only explain XO species, not the majority of species with a Y-chromosome!

Did prokaryotes arise from eukaryotes?

Endosymbiosis theory refutes Senapathy
    Mitochondria (see illustration) are organelles in all eukaryotic cells; they are crucial for the energy supply of the eukaryotic cell; they multiply independently within eukaryotic cells in a simple asexual fashion (just like bacteria!); their DNA is circular (just like bacteria!); the genes are intronless (just like bacteria!); have have little noncoding DNA and few intergenic regions between genes (just like bacteria!); are haploid (just like bacteria!); are exclusively inherited from the mother (maternal transmission) and have their own DNA (37 genes in vertebrate animals) which is autonomously copied. In every respect, mitochondria resemble the prokayotic counterparts more than those of eukaryotes. None of these facts is controversial. These facts support the hypothesis that mitochondria were once free living single-celled prokaryotes. This hypothesis is called endosymbiosis theory and was proposed by Lynn Margulis in 1970 (Senapathy knows this on pages 231, 598). Initially rejected by biologists as too speculative, the theory was accepted by evolutionary biologist John Maynard Smith as early as 1975 in his The Theory of Evolution. That was 19 years before Senapathy published his book (1994). The entire DNA sequence of the human mt genome - 16,569 nucleotides - was determined in 1981 (249), 13 years before the publication of Senapathy's book. It was relatively easy to identify the bacterial ancestors of the mitochondria in 1985 (246,p.177). The theory is now the standard view in biology and evolution textbooks (5). Nobel Prize winner Christian de Duve said about the proofs for the bacterial origin of mitochondria: "In the opinion of the vast majority of investigators, these proofs are conclusive." (6). Grauer and Li (2000) in Fundamentals of Molecular Evolution state "the molecular evidence is now overwhelmingly in favor of the endosymbiotic theory". What Senapathy has to say is this:

"Some scientists have suggested that eukaryotes were formed by "endosymbiosis"... Although there exists some resemblance between mitochondrion and bacterial cells, the origin of the nucleus in the eukaryotic cell is still considered to be a total mystery." (p. 231).

Energetics refutes Senapathy
Mitochondria bestowed upon their eukaryotic host 10⁵-10⁶ times more power per gene than a prokaryote. Mitochondria allowed their host to evolve, explore and express 200,000-fold more genes with no energetic penalty. Eukaryotes harbour approximately 12 genes per Mb, bacteria 500-1,000 genes per Mb. The high gene density and small protein size of bacteria can be explained in bioenergetic terms. "Prokaryotes cannot have evolved from eukaryotes, because the energy per gene required to bring forth the complex eukaryotic starting point for prokaryotic evolution under such views requires a prokaryotic endosymbiont to begin with" (131).

Termites refute Senapathy
Termites mostly feed on dead plant material, generally in the form of wood, leaf litter, soil, or animal dung. This is a problem if termites originated independently in a primary pond. To survive they immediately need other organisms (pants, animals, in other words: an ecosystem). Furthermore, to digest wood (cellulose) termites (eukaryotes) need bacteria (prokayotes) in their hindguts. A termite never could originate and survive in the primary pond, because prokayotes could not originate in the primary pond according to Senapathy.

Immune system of eukaryotes 28 jul 11
The immune system of eukaryotic animals is a problem for Senapathy. The function of immune systems is to combat bacteria. Bacteria are prokaryotes. According to Senapathy eukaryotes arose from the primordial pond and prokaryotes later developed from eukaryotes. What's the point of having an immune system if there are no bacteria? Individuals without immune system would survive, and since genomes are fixed, eukaryotes could not 'evolve' the necessary genes (HLA genes) later when encountering pathogenic bacteria.

Chloroplasts contain DNA   3 Dec 2011 Several researchers proposed that chloroplasts evolved from bacteria (endosymbiosis) in the late 19th century on the basis of microscopic study of plant cells (246, p.44) and again in 1905 and 1907 (244). In 1962 Hans Ris and Walter Plaut demonstrated DNA in chloroplasts in plants (245). This is not an obscure publication, it has been cited at least 15 times between 1964 and 2011 (it is not known in wikipedia). In 1967 Lynn Margulis under the name L. Sagan concluded that not only chloroplasts, but also mitochondria evolved from endosymbiotic bacteria (246, p.44). In 1970 she published her paradigm-changing book Origin of Eukaryotic Cells. In 1978 Robert Schwartz and Margaret Dayhoff proved the endosymbiosis theory (248). Senapathy could and should have known all this in 1994. Secondly, chloroplasts are derived from free living cyanobacteria. That means those cyanobacteria must have existed before eukaryotic plants. This contradicts Senapathy's scenario in which bacteria evolved from eukaryota.

All mammals require a mother

© Lennart Nilsson (1990) Human embryo with umbilical cord. The umbilical cord is the link between mother and embryo and symbolizes dependency.

genome
Would the first human genome include genes for implantation, placenta, umbilical cord? What's the point? This is a dramatic problem because warm-blooded animals with a constant body temperature require a tenfold increase in energy expenditure above cold-blooded animals (101). Does the primordial pond have a temperature of precisely 37 °C?
Even a 100% accurate and complete human genome sitting in a cell does not have a higher probability of survival than any random genome. It could only survive when it is self-supporting: when it could get its own food (adult). Until that it really is a kind of parasite. The human genome is simply not designed to be self-supporting in a primordial pond at the one cell stage and many years after that.

viviparity
Viviparity means the embryo develops inside the body of the mother. The best example is placental mammals. Another group is the pouched marsupials like the kangaroos and koalas of Australia. At birth, the baby kangaroo is no larger than a peanut, a blind, pink, hairless fetus-without-a-whomb that must crawl on its own through the mother's fur into the pouch. It drinks milk from a teat (122). However, scorpions, some sharks, some snakes, and velvet worms also are viviparous. Roughly 20% of non-avian reptile species (lizards, snakes) give birth to live offspring (viviparity).

birth
Other problems: if the human embryo is in the water of the primordial pond during nine months, how does the sudden transition to air breathing (usually called: 'birth') happen? Who helps the baby out of the water to prevent death by drowning? After normal birth fetal haemoglobin (a crucial oxygen-carrying protein) drops off and the adult version kicks in. How is this regulated? Timing?
Babies have average birth weights around 7.5 pounds. In the primordial pond, the baby could grow to any size before 'birth', because it does not have to pass the birth canal of its mother. Females have wide hips and a large enough pelvic opening that enable babies with big brain sizes to be born. A real genome 'knows' to start the delivery at the right size of the baby. How does a human genome in the primordial pond know about the nine months? Timing of birth in humans is under genetic control (207). Does the mouse genome know that it is sitting in smaller animal and needs to deliver in a shorter time?
    The human baby is born premature when compared with chimpanzees. The first teeth appear only after 6 - 12 months. The head of the foetus is still small enough to pass through its mother's birth canal. One of the consequences is that humans at birth are utterly helpless (42). The human brain doubles in size in the first year of life and achieves 95% of its adult size by the age of 5 (although white matter grows at least to age 18).

energy
It takes roughly 13 million calories to rear a human baby from birth to nutritional independence at around age 18 or older (168). Big brains are so metabolically expensive that primates must postpone the age of reproduction in order to build them. High fecundity requires at least an extended family with fathers and grandmothers around to help provision and care for the young (109).

hormones
Amazingly, in order to be a healthy individual, in Senapathy's scenario the first female genome would not need hormones for ovulation, menstruation, womb, pregnancy, and lactation. If no hormones are necessary, then genes for hormones are unnecessary. The genomes would be different.

immune system
The mother must tolerate a fetus that is an antigenically foreign body. The human fetal immune system has the ability to recognize noninherited maternal alloantigens and must somehow tolerate them. Mother and fetus must prevent autoimmunity (attacking own tissues).

sex organs
The fetus has internal and external sex organs which are useless in the womb. Furthermore, sex organs would be unnecessary for survival of the first individual. There is no reason to expect that the primordial pond would produce complete male and female genomes. Sex organs simply do not contribute to the health and survival of the first individual.

parental care
Why should the first female have a pair of breasts which grow considerably during puberty? A pair of breasts does not contribute in any way to the health and survival of the individual possessing them. They are a burden and a risk (breast cancer). Additionally, how does Senapathy explain that only 50% of the individuals have breasts? The first individual needs food, needs to escape disease and predation to survive, not sex. So why is the primordial pond not producing sexless individuals forever? (25).
Why are parents (especially mothers) motivated to care for their young? It certainly does not help the survival of the parents themselves.

complete genomes
Returning to the issue of complete genomes: what is a complete genome? If spontaneous generation of genomes were nature's method for producing animals and plants, then a healthy sexless individual is viable and complete. As an illustration: only one missing gene can make healthy male or female mice sterile (27). On the other hand one needs a few hundred genes, I guess, to add maleness and femaleness. To evaluate 'independent birth' we need to eliminate our deeply rooted prejudices about the necessity of sexual reproduction. Senapathy should take his primordial pond serious and reason from the point of view of the primordial pond, and resist relying on the benefit of hindsight.

altricial species
In general, in bird and mammal biology altricial species ("requiring nourishment") are those whose newly hatched or born young are relatively immobile, have closed eyes, lack hair or down (naked), and must be cared for by the adults. Altricial young are born helpless and require care for a comparatively long time. Among birds, these include, for example, herons, hawks, woodpeckers, parrots, owls and most passerines. Rodents and marsupials are altricial, as are cat, dog, fox, lion (they are carnivores) and humans. Altricial species usually have relatively short gestation periods. Altricial individuals, if ever 'born independently', don't survive.

imprinting
The best known form of imprinting is filial imprinting, in which a young animal learns the characteristics of its parent.

©Antal Festetics, 1983

Common descent versus independent origin

similar species of a distinct creature millions of distinct independently-born creatures Fig 3. Senapathy, p.462

pheasants ducks dogs   cats   horses creation of basic types Fig 4. Paul Nelson (7)

"slightly changed creatures could also be produced in the primordial pond by mechanisms of genome mixing and genome alteration and or restructuring" (p.455).

1. This is again contradicting independent origin;
2. If 'genome mixing' completely mimics common descent, then there is no observational difference of his theory and common descent
3. 'genome mixing' and 'in part or full' is arbitrary, too vague, too 'cheap', too 'easy' a maxiumum of freedom
4. it does not make sense that anything goes at the moment that genomes originate and millions of years thereafter all genomes are frozen (immutable)
5. It is impossible to refute such a theory. When showing evidence that refutes independence, Senapathy always can claim 'my theory can explain this by a common pool of genes and genome mixing'. We do not learn anything new about nature.

The role of randomness and improbability

The role of natural selection

©Dries Buytaert

Fig 5.

Fig 6.

Fig. 7. Later Senapathy produced this figure on the internet, demonstrating the extensive involvement of natural selection (although he disingenuously used different names such as 'failed trials', 'filter', 'window', 'pinhole'). He also uses the word 'natural selection', contradicting his book title "...Showing That Evolutionary Theories Are Fundamentally Incorrect."

Ecology and Climate

The role of mutation: exploring DNA sequence space

"Mutations in a genome can only lead to normal individual variations, or to genetic defects, which are absolutely (28) useless for organismal evolutionary change"(p.46)

"the genome of every independently born creature is unique and unchangeable into that of another unique creature, and therefore is essentially immutable." (p.6)
"a snail can give rise to many different snail varieties, but never to a crab or a sea star." (p.46).

Exploring DNA sequence space

Random origin of a human genome

The role of adaptation: random perfection

Fig. 8. Is the match between the extreme long spur of the orchid and the extreme long tongue of the moth an accident? © image Sinauer 2005 (60)

Fig. 9. Which genome originated first: the humming bird genome or the flower genome? How could they survive and reproduce without each other? Is this mutual adaptation merely a genome accident? © image Sinauer 2005 (60)

The genome is blind
"The genome is blind and cannot visualize the existing niches and environments. Therefore, millions of bizarre phenotypes must be produced in a species for the selection of one useful structure. (p. 89, see also p.75. my emphasis).

This looks like a devastating argument against Independent Origin. Surprisingly, these words are written by Senapathy himself. He is perfectly aware of the problem that genomes are blind. Remarkable for someone rejecting natural selection, he uses the word 'selection' in the above quote! He writes: "the genome of the reptile or the wingless invertebrate did not "know" that there was a medium called air in which the animal could fly if it developed a wing for its host" (p.89). "To the genome of an animal that lacks a wing, the new genes that code for the feathers have no meaning." (p.75). Surprisingly, he turns this into a problem for Darwinism by stating that an almost infinite number of random mutations should occur in order to arrive at a wing. 'Infinite' is exaggerated, but in principle Independent Origin has the hypothetical advantage compared to Darwinism, and that is because it sidesteps the need to modify existing structures because all organisms originate de novo. Consider for example the origin of land animals. The vertebrate transition from water to land requires changes in a variety of functional systems including feeding, respiration, support and locomotion. The key question is: is it easier to produce an organism from chemicals or to modify an existing organism? How many random genomes are needed to produce a land animal or a flying animal from scratch compared with modifying aquatic animals or non-flying animals? That must be billions of times more. In the theory of evolution the origin of flight starts with a fully functional reptile or insect (evolution is cumulative). Senapathy has to produce a fully functional animal plus a pair of fully functional wings from a random genome. Which of the two is the most difficult task? He is also fully aware of the fact that birds have additional unique properties. Again: the probability of producing all those features from scratch must be very much lower than adding them one by one to an existing animal. Even if Darwinists would not have any idea about the genes and mutations involved, still the probability of adding features to an existing design must be orders of magnitude easier than developing a complete animal from scratch. Birds inherit all their features (metabolism, anatomy, cell structure, behaviour, reproduction) from reptiles, tetrapods, multicellular organisms, eukaryotes, and single celled ancestors. The primordial pond has to reinvent everything as many times as there are species. Rejecting common descent comes at a huge cost: it equals reinventing the wheel a billion times!
See also: Common descent versus independent origin and: The role of natural selection).

The role of time: the chronological order of life

Figure 11.1. The chronology and time table of the independent birth of organisms. Chapter 11: 'A New Look at The Fossil Record', page 497.

first humans did appear 6-7 million years ago Old World Monkeys: 25 -33 million years ago first bats, dogs, weasels, elephants: 30 - 40 million years ago first placental mammals (rabbits, whales, rodents): 60 - 65 million years ago first mosquitoes, honeybees: 65 - 70 million years ago first turtles: 65 - 190 million years ago first butterflies (Lepidoptera): 150 million years ago first birds: 155 million years ago first frogs, crabs: 135 - 190 million years ago first flowering plants appeared about 135 million years ago; grasses appeared around 94 million years ago first sex chromosomes (XY) appeared some 200 million - 300 million years ago first amphibians: 360 million years ago first tetrapods: 375 - 363 million years ago reptiles did not appear before 416 million years ago first land plants appeared 465 - 470 million years ago; plant with leaves appear with a delay of 40 million years; trees: 475 million years ago. fish with jaws appeared: 416 - 359 million years ago jawless fish appeared: 500 - 435 million years ago multicellular animals: 635 million years ago eukaryotes: 1,000-1,300 million years ago cyanobacteria: 2.15 billion years ago stromatolites: 3.4 billion years ago The reader is advised to have a look at: TimeTree: The Timescale of Life

source

Furthermore, many forms of life appeared in the fossil record before the start of Senapathy's primordial pond (600 Mya). There is solid evidence that life was present on the earth more than 3 billion years ago. Conclusion: life appeared 2400 million years before the start, and 500 million years after the end of Senapathy's primordial pond. Secondly: the first fossil animals found in the oldest layers were creatures that lived in the sea (trilobites, brachiopods), only later animals and plants living on land are found. Why? The first animals on land were amphibians and reptiles. Reptiles dominated the earth before mammals appeared. Mammals appeared much later. This was known before Darwin (1859). There was little overlap between "the age of reptiles" and "the age of mammals". Traces of humanity did not appear until the very end of the record. This is chronolgy.

Anyone proposing a non-evolutionary explanation for the origin of life and species must start with explaining the fossil record as known in 1859 and everything that has been learned since then. Senapathy did not do this. This fossil record cannot be explained by a primordial pond that produces every species at the same time.

2 Jun 11 Fact: Nitrogen cycle: bacteria first Proteins and DNA contain Nitrogen (N). The atmosphere of the earth contains enough nitrogen (78%), but remarkably, animals and plants can not use it. Only nitrogen-fixing bacteria (prokaryotes!) can use nitrogen from the air. (Some fixation occurs in lightning strikes). This imposes a chronological order: first bacteria, then plants, then animals. So, independent origin of animal and plant genomes is impossible. In Senapathy's genome-centered view the chronological and ecological context is absent. See: Nitrogen cycle (wikipedia)

How many primordial ponds?

Why not propose thousands or millions of primordial ponds in stead off one? It could make independent origin much and much more easier! Maybe Senapathy needs "a common pool of genes in the same primordial pond"? (see: §13). That suggests he needs just one pool. If necessary he claims a separate primordial pond ('Burgess pond', p. 324, 328) without discussing what it means for the universal genetic code. Why not propose a primordial pond that lasts millions of years? In the Preface he notes that numerous organisms might have been assembled more or less simultaneously within the primordial pond (page x). Amazingly, Senapathy did all this! He claimed that there exists a single primordial pond (p.8), two distinct ponds (p.500), many (p.502) and 'millions of small and large ponds must have existed on the primitive earth' (p.214). Please note that millions of separate ponds make the existence of a universal genetic code an unsolved mystery, to put it mildly.

Extinctions and recoveries

The independent birth theory does not predict a specific order of appearance or extinction in time because genomes are randonly generated in time. However, the fossil records shows for example that "the extinction of dinosaurs at the Cretaceous/Paleogene boundary was the seminal event that opened the door for the subsequent diversification of terrestrial mammals" (133). For the first 140 million years of their evolutionary history, mammals were small (up to 15 kg). Such a pattern should not exist according to the theory of independent birth.

How does the theory of independent origin deal with the big extinctions and recoveries? The figure shows 5 major mass extinctions. Each is followed by recovery of the number of species. Overall, there is a clear increase in the number of species from 600 million years ago to today. This would require that primordial pond(s) must have been active continuously from 600 million years ago up to today. Figure: Nicholas Barton et al (2007) Evolution, p. 283.

Macroevolutionary trends in animal diversity and gene regulation show that there is a chronological order in the appearance of animal groups and regulatory sequences contradicting expectations of random origin in a primordial pond. Source: (221).

The role of place: the biogeography of the origin of species

Independent origin and the clumpiness of morphospace

• Why do animals take the forms they do, and not others? Why are all land vertebrates 'tetrapods', while none have six or eight legs?
• With a few exceptions, all mammals and birds are warm-blooded, and all reptiles, insects, arachnids, amphibians and fish are cold-blooded (218). Why is this, if they are independently born?
• Why do birds (of prey) have no teeth? It would be advantageous for larger pieces of food which cannot be swallowed in one piece. Why don't birds have a third pair of arms to handle their food? (since they can't use their wings for that task). Humans, apes, squirrels can use their hands for handling food. Why aren't there birds with internal gestation?
• What is the matter with genomes that insects are more numerous than any other type of animal, accounting for 80% of species?
• What is the matter with genomes: birds have remarkably small genomes, averaging 1/2 to 1/3 of the size of typical mammalian genomes. Why should that be when all eukaryotic genomes arose independently? Small genome size is intriguingly correlated with flight. Bats, compared to other mammals, have small genomes, and flightless birds, compared to other birds, have larger genomes. (220)
• Why does not one of the almost 40,000 species of spiders fly? Why do all spiders have eight legs? Why do all spiders produce silk? Why are all spiders predatory and not herbivorous?
• Unlike most animals, female birds are the heterogametic sex, having the equivalent of a human Y chromosome, called the W chromosome (so females are ZW, males ZZ). Why is this property not randomly distributed over animals and birds?
• Why does the domain of mammalian carnivores contain a large cluster of cats, another of dogs, a third of bears, leaving so much unoccupied morphological space between?

The primordial pond is a free lunch

Incompatible requirements for a primordial pond

Furthermore, if born, why and how do organisms migrate from the primordial pond to all those different locations? Some organisms only survive at deep sea, hydrothermal vent communities are found at depths ranging from 1,500 to 3,200 m. Giant tube worms (chemoautotrophs), in the absence of sunlight, subsist on hydrogen sulfide found in the warm waters surrounding vent communities. There is evidence for living prokaryotic cells in 1626 meters below the sea floor sediments that are 111 My old and at 60° to 100°C (79). The bacterium D. audaxviator lives at 2.8 kilometer depth in a South African gold mine and is lacking a complete system for oxygen resistance, suggesting the long-term isolation from O₂. That means it is damaged by oxygen (102).
Emperor penguins live in probably the most extreme conditions endured by any warm-blooded animal on earth. They even breed in the depths of the Antarctic winter at temperatures of -30°C (-22°F). They have so many cold adaptations that in warmer weather, overheating can be a problem. So, if the primary pond is located in moderate or tropical regions they will die from overheating.

Eggs incompatible with water

In the primordial pond organisms develop from 'egg cells'. Please, have a look at the cover illustration again: not accidently, there is no bird or mammal creeping out of the primordial pond. Bird eggs do not survive in water (apart from the requirement of incubation). Saltwater crocodiles, marine iguanas and sea turtles, although marine, lay eggs on land. Please have a look at the cover illustration: a turtle is coming out of the primordial pond! However, all turtles lay eggs on land. Also, reptiles cannot successfully lay eggs under water because gas exchange across the eggshell is much slower in water than in air.

Bar-headed goose. © Chalto Digital Images

If one wishes to escape from incompatible requirements, why not propose thousands or millions of primordial ponds in stead off one? It could make independent origin much and much more easier! For example it would make it easier to explain the unusual breathing system in some dinosaurs, a group called Saurischian dinosaurs who lived at a time when the oxygen level at the surface of the earth was only 10 percent (103). Alternatively, why not propose a primordial pond that lasts millions of years? (see: §18 The role of time: the chronological order of life). The secret could be that Senapathy needs "a common pool of genes in the same primordial pond"! (see: §13 Common descent versus independent origin).

The origin of life

The origin of life
In modern science the Origin Of Life field has grown into a separate research field with strong connections to astrobiology, organic chemistry and geochemistry. According to the most recent textbook of Evolution (89) there are seven criticial steps in the origin of life:

1. the generation of simple organic molecules from inorganic molecules
2. chemical "evolution" to produce more complex organic molecules and primitive metabolic netwerks
3. the origin of self-replication and the creation of "genotypes"
4. compartimentalization and the creation of cells
5. the linking of genotype and phenotype
6. the origin of the genetic code
7. the takeover of early replication systems by one involving DNA

The RNA World
The discovery that RNA molecules can act as catalysts provides a possible solution to a long-standing dilemma:

• DNA encodes the genetic information of proteins
• proteins cannot self-replicate (except prions)
• DNA replication and transcription requires proteins

1. a repository of information (in its sequence of nucleotides)
2. a catalyst

Multiple origins of life hypothesis
Raup and Valentine (140) propose multiple origins of life: "The probability of survival of life is low unless there are multiple origins, and given survival of life and given as many as 10 independent origins of life, the odds are that all but one would have gone extinct, yielding the monophyletic biota we have now." This mainstream hypothesis does not contradict common descent of all life. It only proposes that there must have been many origins, but they did not survive except one which formed the universal tree of life. Senapathy proposes independent origin of all species.

• See also: §25: What is life? in which I argue that one must first know what life is, before one can start to explain its origin.
• See also: Exploring Life's Origins. (animations!)

The final refutation of independent origin

What is life?

1. a chemical motor (metabolism) that supplies energy to synthesise compounds necessary for the other 2 subsystems and is stable;
2. a membrane which keeps the other 2 subsystems together, protects against dilution and is itself stablel;
3. an information-carrying subsystem (for example DNA) which enables reproduction of the 3 subsystems.

Rerun the tape of life

PLOS ONE article

I tried to decipher the logic of his argument in the PLOS article. Despite I studied his argument for years, it is not easy. I guess, he does not want to defend the idea that the present-day human genome is random with respect to the frequencey of stopcodons. No scientist would want to do that. A random genome could not produce a human being. On the other hand, nobody can argue against the claim that "The presence of three stop-codons for every 64 codons limits the average ORF [Open Reading Frame] length to about 60 bases in random DNA" ('random DNA' is a computer generated random string of four different symbols). What he seems to argue is that, despite the predominant non-random nature of present-day genomes, exon length still has a random signature.

Figure 7A. The ROSG model. Origin of an eukaryotic gene from primordial random DNA.
ORF = Open Reading Frame, is DNA sequence between two stopcodons.
Red: coding sequence is an exon. Stop codons occurred too
frequently to allow functional proteins to be encoded in random DNA.
That's why processing is necessary. Please note there are no startcodons.

When?
Senapathy does not distinguish clearly between the timing of the different events: 1) the origin of the very first DNA sequences, 2) the processing of those sequences, 3) subsequent genome evolution during 2 billion years. But prebiotic environments are completely different from those of a living organism. Irrespective of when (106) this processing occurred, after 'splicing together short coding pieces', exons lengths, gene lengths and genomes are not random anymore. Any selective processing of random DNA makes it non-random. Any non-random removal of stopcodons change the statistical properties of the sequence. If present-day exons are a combination of shorter pieces joined together, than by definition current exon lengths are not random.

The mechanism
His figure shows the combination of 4 small exons into one large exon, but any exon length can be explained in this way. An arbitrary number of exons with arbitrary lengths can be joined to an arbitrary number of new exons with arbitrary lengths. Also, an arbitrary number of exons may stay unmodified. Exon length distribution is the main thing Senapathy wants to explain and he introduces a mechanism that changes them in an unspecified way. Why do introns still exist? Why are there still so many introns in our genes? Why did his mechanism not eliminate all introns? Senapathy observes present-day exon lengths and postulates a hypothetical mechanism that produces exactly the exon sizes of today. That does not add anything to our knowledge.
My own suggestion would be: it is true that stopcodons would limit gene length, but a far more simpler solution would be elimination of stopcodons by a one-base mutation of the stopcodon in the context of living organisms. That is a far more simple because it does not require complicated splicing machinery. Certainly under prebiotic conditions where no functional enzymes are present. He did not give evidence that this complicated processing is possible in prebiotic chemistry. He stated that functional proteins cannot be encoded in genes with average ORF length of about 60 bases.

Facts
In addition to the contradiction of his own model with his own data (called 'non-confirming' data by Senapathy), two types of evidence are contradicting his hypothesis: too many short exons and too many long exons. Humans have 170 exons of length up to 25 bp (107) which is significantly lower than the expected size of 60 and exon sizes up to 2087 bp exist (108) which is much outside the predicted maximum. The length of an average human exon is 126 bp which is more than twice the expected 60 bp.
Possibly, his ideas and data about the origin of splice signals (Figure 7B, not shown) are interesting. I would suggest submitting it to scientific journals such as Genomics.
Finally, the idea that the very first DNA sequence must have been random, is plausible only if that idea is part of a plausible 'DNA-first' theory of the origin of life.

Nature Precedings articles

History
The Conclusion of the article starts with: "This work does not claim to provide historical details of early evolution." (p. 9). You can focus your Origin of Life theory on any aspect you are interested in. Maybe you are not interested in the history of life. That's ok. However, the moment you want to test your theory, you cannot ignore history. Simply because your theory could conflict with the fossil record. And it does. Eukaryotes include vertebrates like birds, whales, elephants, horses and humans. They easily fossilize. If they are produced in the primordial pond, why are those fossils not found during the 'Cambrian explosion of multicellular organisms'? Where are the fossils? See: §18: the chronological order of life.

Self-assembly?
Some of his claims seem to be more modest than earlier claims: "Our findings demonstrate that complete split genes encoding complex proteins could have arisen within a minute amount of pre-biotic random DNA, explaining the origin of biological information and serving as the basis for the evolution of the very first genome." (p. 2. my empahsis). And in the conclusion he writes: "that these genes could have been used in the self-assembly process to create countless eukaryotic genomes" (p.9 my emphasis). So, Senapathy does not explain genomes (strong claim), but genes (weak claim). The word 'evolution' in a non-evolutionary theory? Self-assembly of genomes? This is pure magic! He provides no details, no mechanism, no probabilities, no evidence for self-assembly of genomes. That means that the most important part of his theory is left unspecified. Again: explaining genes does not explain genomes. Genomes are not arbitrary collections of arbitrary genes (See: § 5). What determines whether a specific collection of genes is a genome? Sooner or later one must invoke selection of viable collection of genes, and death of inviable collections of genes. So, the crucial step to genome formation in the independent origin scenario would invoke the Darwinian principle of natural selection! Question: could it be that if genome formation depends on self-assembly of isolated genes, that the larger the genome, the lower the probability of successful self-assembly of that genome? It must be.

Genetic code
The stopcodon statistics story, which was an important part of the PLOS article, is not defended explicitly in this article, although he refers to it. The stopcodon issue is part of the genetic code problem (see 'The elephant in the room' above). The genetic code problem, the main ingredient of the origin of life problem, is stated and dismissed in a shallow way in a two-sentence paragraph. This is very disappointing from a scientific point of view. (See: § 5)

Figure 1. The common ancestor of eukaryotes, bacteria, and archaea may have been a community of organisms. +M = endosymbiosis of mitochondrial ancestor. Kurland et al, ©Science

There is an even more remarkable mainstream publication of J.E. Darnell (1978), not cited by Senapathy as far as I know, which claims "that eukaryotes evolved independently of prokaryotes" for exactly the same reason as Senapathy: "noncontiguous sequences in eukaryotic DNA" and that eukaryotic DNA "may reflect an ancient, rather than a new, distribution of information in DNA" (169). Martin and Koonin ((170) say about this: "James Darnell submitted similar ideas at a time when the issue in early evolution was how to generate long coding sequences from scratch" (my emphasis). From scratch? (This is exactly Senapathy!). At a time? Was it a mainstream issue at the time? But has become irrelevant? Because of what? Mysterious! Whatever, Darnell did not claim that complex multicellular eukaryotes could have originated from prebiotic random DNA.

Anyway, it is a logical mistake to think that gaps in knowledge of eukaryotic origins is evidence for any alternative theory. Senapathy needs positive evidence for his theory. (See also: § 11).
Senapathy uses references to the literature to support his views, which do not support his views at all. For example: "Even after the knowledge that eukaryotic split genes may have been the very first genes became widespread, ..." (p.7, my emphasis). This is a serious misrepresentation of the literature. What the publication (153) says: "the proposal that introns arose before the origin of genetically encoded proteins and DNA," (my emphasis), which refers to a RNA world (self-splicing RNA's). Nobody in the literature claims that complex eukaryotic genomes (like the human genome!) were produced at the time of the origin of life. There is simply no evidence in the fossil record of vertebrates in the Cambrian fossil record. Nobody claims that the "last eukaryotic common ancestor had an intron-dense genome" means that these were the first forms of life.
Senapthy's interpretation of the relevant scientific literature appears to be idiosyncratic, unorthodox, and often erroneous. His references are so numerous, that it is a huge undertaking to check all his references.

Introns-Early — Introns-Late
Senapthy's theory is beyond the Introns-Early (IE) versus Introns-Late (IL) controversy. It would not be correct to label his theory as 'Intron-Early'. If anything, it could be called 'Intron-First' (IF), (but the context of IF is the RNA world). Introns-Late is certainly incompatible with his theory. In Senapathy's theory introns and exons simply do occur in random DNA. It is a static phenomenon. Introns do not have biological causes. Introns did not invade genomes. The mainstream view, whether Introns-Early or Introns-Late, is that introns are a dynamic phenomenon: they invade existing genomes like parasites. In Senapathy's theory it makes no sense to talk about 'mechanisms of intron loss and gain'. They were just there from the beginning.
Mainstream science agrees with Senapathy in one point and that is that introns have evolved extremely early: "introns that currently reside in eukaryotic genes, after all, do derive, through an uninterrupted lineage of selfish elements, from primordial genetic elements." and "introns have evolved extremely early, very likely, earlier than cells themselves." (Koonin 165). Although Koonin uses the suggestive phrase "primordial pool of genetic elements" (233), big differences are that "the primordial genetic pool is believed to have evolved from a pure RNA world to a RNA-protein system to the modern world of the Central Dogma (DNA-RNA-protein)" (165), and that the method was descent with variation (tree of life). Ford Doolittle: "Really we know nothing about how genes arose, and to suppose that they sprang full blown and full length from noncoding polynucleotides seems to me more of a stretch than to imagine that they were cobbled together from smaller oligopeptide-encoding modules" (165).

Summary and Conclusion

• science should seek a natural explanation of the origin of life
• prokaryotes very rarely have introns, have high gene densities, low-entropy, compact, relatively small genomes
• eukaryotes have many large introns, have low gene densities, have high-entropy, noisy, large genomes
• it is possible to find the sequence of any eukaryotic gene in computer generated random strings of A,T,C,G if the sequence is long enough (262)
• stopcodon statistics in random computer DNA necessary follow from the fact that there are 3 stopcodons in 64 codons
• mainstream scientists use the concept "primordial gene pool" (233)

1. reduction of life to genomes (genome-centric view of life, ignoring cells, ignoring chromosomes)
2. reduction of genomes to genes (reduction of genomes to an arbitrary collection of genes)
3. reduction of genes to exons (ignoring intron sequence).
4. reduction of exons to information (reduction of biology to statistics, ignoring chemistry).

The second major error (I became aware of this only after nearly 10 years) is that even a 100% accurate human DNA sequence without a cellulair context has no more meaning than a random DNA sequence of the same length. Even if a correct human sequence of 3 billion base pairs would be found in a random sequence, including all introns, exons, splice sites, regulatory sequences, promotors, enhancers, etc, would be present as a double-helix and in a diploid heterozygote state and correctly distributed over 46 units (simulating human chromosomes; 2n=46, XY or XX pair), and even if all sequence characteristics of the chromosomses were present (telomeres, centromeres), and even admitting that 95% of the genome is 'junk-DNA', the sequence would be as dead as a doornail! The human genome sequence could not even produce a human. The sequence would not even be 'living' (see: here). Even if the most simple prokaryote (a bacterium) would have contained sufficient introns, it could not originate from naked DNA in a primordial pool. Worse, it is completely irrelevant whether there are introns or not. The reason is the same as why a DNA virus is unable to reproduce outside a living cell (viruses are intracellular parasites): a naked DNA sequence is unable to do anything outside a living cell. There is a profound reason for this error: the genome-centered view of life ('genetic determinism'): (219) THE SEQUENCE IS NECESSARY AND SUFFICIENT TO CREATE AN ORGANISM This is wrong if applied to the origin of an individual (216). But Senapathy got carried away by the idea, took it too literally, and transformed it into: THE SEQUENCE IS NECESSARY AND SUFFICIENT TO EXPLAIN THE ORIGIN OF LIFE The idea that The Sequence is necesssary and sufficient to create an organism is an absolute requirement for independent origin. For, if other factors than The Sequence would be required, The Sequence itself could never explain the origin of life. The next step is: let the Sequence be created abiotically by the Primordial Pond and the origin of life would be explained. Both scenarios (1) and (2) fail for the same reason as why a virus could not be the explanation for the origin of life: The Sequence depends on other factors to do anything. Both naked DNA and a virus need a living cell to do anything. A virus, despite containing genetic information, cannot be called 'living' because it does not and cannot do anything itself. Just as naked DNA. Just as a sperm, despite the fact that a sperm has a complete human genome. A sperm itself cannot produce a human. It needs an egg cell. These objections are so fundamental that no future developments can change that situation.

Appendix: Genetics Primer

Notes

1. Senapathy: "When I initially tried to explain my theory to my wife, I said, All the organisms could have come about just as they are, independently from the primordial pond. Her response..." (p.295). Please note, she forgot to ask about humans.
2. Source of chromosomes. These chromosomes are not from Senapathy's book. There are no chromosomes in his book. That is the point.
3. Only male honeybees hatch from unfertilized eggs [are haploid], but female honeybees hatch from fertilized eggs [are diploid], therefore that won't help independent origin theory very much. See: Olivia Judson(2002) Dr. Tatiana's sex advice to all creation, p.18 . Hermaphrodites (organism with both female and male sex organs) usually need another individual to reproduce.
4. Helen Pearson: Human genetics: "Dual identities", news feature, Nature 417, 10-11 (2002), 2 May 2002.
5. See for a full exposition for the non-specialist Mark Ridley (2000) Mendel's Demon. Gene Justice and the Complexity of Life (review), Chapter 6 "Darwinian merger and acquisition" is about the far reaching implications of having mitochondria in the cell.
6. Christian de Duve (2002) Life Evolving, Oxford Univeristy Press, p. 141.
7. Robert Pennock (2001) Intelligent Design Creationism and its Critics, p. 685.
8. S.G. Gregory et al (2002) A Physical map of the mouse genome. Nature AOP, published online 4 August 2002.
9. Carina Dennis and Richard Gallagher (2001), The Human Genome, p.120: "The largest apparently contiguous conserved segment in the human genome is on chromosome 4, including roughly 90,5 Mb of human DNA that is orthologous to mouse chromosome 5."
10. Similarities found in mouse genes and human's. Nicholas Wade, NewYork Times Science, 5 Dec 2002.
11. Comparision of Human chromosome 4 and Mouse chromosome 5.
12. Comparision of Human chromosome 17 and Mouse chromosome 11.
13. Comparision of Human chromosome 20 and Mouse chromosome 2.
14. A memorable misunderstanding on this site.
15. Evolution (Third Edition) on this site.
16. A Chemist's View of Life: Ultimate Reductionism & Dissent on this site.
17. Ernst Mayr (2001) What Evolution is, p.46. See also: Lynn Margulis(1998) Five Kingdoms. An illustrated guide to the phyla of life on earth, third edition. p.12.
18. Senapathy has a short paragraph What is a "seed cell"? (p.307), in which he uses 'haploid' and 'diploid', but there he neither explains what a seed cell is, nor how a diploid cell arises out of the primordial pond.
19. Portrait of a molecule by Philip Ball. This is a good article for those who think that a genome is just naked DNA. Nature 421, 421 - 422 (2003) (free). Have a look at the beautiful diagram of the 3-D structure of the chromosome showing that a genome is more than just the sequence of the bases! Looking at this image it is clear that Senapathy's discovery about split genes in random DNA is almost irrelevant. He did not explain the massive amounts of highly specialised proteins (histones), which form the complex 3-D structure of the eukaryotic chromosome.
20. Richard Dawkins used the now famous weasel computer experiment to demonstrate the difference between one-step and cumulative selection in The Blind Watchmaker, chapter 3. See also Spetner review.
21. David Foster attributed this argument to Thomas Huxley (see review of Foster's book).
22. Senapathy states (p.222) that the occurrence of the uninterrupted text of Shakespeare is improbable.
23. Senapathy easily contradicts his own theory: "Thus it is possible for the prokaryotic genome to have been derived directly from contiguous genes in the open primordial pond". (p.238)
24. In fact, this question is wrong. There is no such a thing is "the human genome". Only female and male human genomes exist.
25. "the primordial pond could have been productive for a very long geological time" (p.345).
26. "indentifiying exon-intron borders is a notoriously difficult task", Antoine Danchin(2002) "The Delphic Boat", p.238.
27. Charles Spruck (2003) Requirement of Cks2 for the first metaphase/anaphase transition of mammalian meiosis. Science 300 (5619):647. 25 Apr 2003.
28. Whenever Senapthy is uncertain, he says "absolutely". The word occurs 138 times in his book!
29. Even Jesus, the son of God, had a mother. Significantly, this is claimed by people who otherwise accept miracles. However, Adam and Eve did not have a mother and father, but were created as adults. Senapthy's creatures also did not have a father and mother, but at least did not start as adults!
30. A Conversation with James D. Watson, Scientific American, April 2003.
31. David Haig (2002) Genomic imprinting and kinship, Rutgers University Press, p.11. A further reason for the absence of parthenogenesis in animals is that the sperm also contributes the centrosome to the egg which is essential for initial divisions of the fertilized egg (Christiane Nüsslein-Volhard, 2006, p.15).
32. John Maynard Smith & Eörs Szathmáry (1999) The Origins of Life. From the Birth of Life to the Origin of Language. Furthermore, the members of higher levels are composed out of members of lower levels.
33. Graur and Li (2000) Fundamentals of Molecular Evolution. Second edition. p. 136.
34. Donald Forsdyke (2001) The Origin of Species Revisited, p. 103. (see review on this site).
35. Syozo Osawa (1995) Evolution of the Genetic Code, p. 45.
36. Michael Majerus (2003) Sex wars. - Genes, bacteria, and biased sex ratios, p.63,66.
37. Actually, meiosis is more complex. In males, the products of meiosis are four sperm, each sex chromosome in the original diploid cell being present in two of the products. In females of most species, however, only one egg is produced for each parent cell that undergoes meiosis, the other three haploid products together giving rise to the yolk of the ensuing egg. See also review of Mendel's Demon (Unexpected predictions and explanations).
38. Jan Sapp (2003) Genesis. The Evolution of Biology, Oxford University Press, paperback, p.x (Prefeace). This is elaborated in the chapter "Beyond the Genome".
39. M. Lynch (2002) 'Intron evolution as a population-genetic process' Proc. Natl. Acad. Sci. U.S.A. 99, 6118 (2002)
40. Paul Davies (1999) The Fifth Miracle. The Search for the Origin and Meaning of Life. p.119. Very important book!
41. What is known about the function of introns? , Scientific American, Ask the experts/Biology, 1999. Of course Senapathy could not have known this in 1994.
42. Louis Berman (2003) The Puzzle. Exploring the evolutionary puzzle of male homosexuality, p.478
43. Tibor Ganti (2003) The Principles of Life, Oxford University Press. (review). Furthermore, Ganti writes: "A living organism can never be developed from genetic material alone", "An egg, a seed, or a spore must always contain the substances of the cytoplasm". p.126.
44. Freeman Dyson (1999) "Origins of Life", second edition. p.18.
45. J.J. Emerson et al (2004) "Extensive Gene Traffic on the Mammalian X Chromosome", Science 303, nr 5657, 23 Jan 2004, pp. 537-540.
46. However, retrogenes are known for a long time. Examples of intronless retrogenes are: PGK (1987), calmodulin gene (1987), globin gene (1987), actin gene (1985). See Wen-Hsiung Li (1997), p.347.
47. S. J. Gould (2002) "The Structure of Evolutionary Theory", pp 252-253, 325, 527-528, 1174 (slightly adapted).
48. Solving the origin of life without the origin of species is difficult enough. However, even the origin of life itself is difficult enough because it commonly includes the origin of the genetic code. Hungarian chemist Gánti simplified the question by distinguishing between the origin of life an the origin of the genetic code.
49. Motomichi Matsuzaki et al (2004) 'Genome sequence of the ultrasmall unicellular red alga Cyanidioschyzon merolae 10D', Nature 428, 653-657. 08 Apr 2004. This species has 5331 genes, only 26 genes have introns.
50. Iris Fry (2000) The emergence of life on earth, p.56, 170.
51. Paul G. Falkowski and Colomban de Vargas (2004) Shotgun Sequencing in the Sea: A Blast from the Past? Science, 304, 58-60, 2 Apr 2004.
52. Iain Cheeseman and Arshad Desai (2004) Cell division: Feeling tense enough?, Nature, 428, 32-33, 4 March 2004.
53. Radu Popa (2004) "Between Necessity and Probability: Searching for the Definition and Origin of Life", p. 95-96. [ 18 June 2004 ]
54. David Bainbridge (2000) Making babies. The science of pregnancy, page 35-36.
55. Philip Ball (2004) "Synthetic Biology: starting from scratch", Nature, 431, 624-626 (7 Oct 2004). "Bacterial genomes are within the range of current DNA-synthesis technology" says John Mulligan, president of the DBA-synthesizing company Blue Heron Technology. But bacterial genomes must be embedded within a cell and its attendant biochemical machinery, making them much harder to synthesize than viruses.". [ 9 Oct 2004 ]
56. Why are stem-cells so important? Stem-cell biology is the second pillar of twenty-first-century biology. If a genome were enough, why are stemm cells so important for medicine? See: Ann Parson (2004) The Proteus Effect: Stem Cells and their Promise for Medicine. [ 24 Oct 2004 ]
57. Mark T. Ross et al (2005) "The DNA sequence of the human X chromosome.", Nature, 434, 17 Mar 2005, 325-337.
58. Christian de Duve (2002) Life Evolving, p.38.
59. Gil Ast (2005) The Alternative Genome. Scientific American April 2005 pp40-47.
60. Douglas Futuyma (2005) Evolution, Sinauer Associates, page 53 and 440. (figures adapted for the web).
61. This is similar to explaining everything by saying 'God created the perfect fit between organism and environment'.
62. Large genomic differences explain our little quirks, Nature, 19 May 2005, 252.
63. Patrick Forterre (France) argues "that bacteria probably evolved more recently, and that LUCA was in fact a eukaryote", NewScientist 3 Sept 2005, p.28. (LUCA=Last Universal Common Ancestor). So Forterre seems to suggest that bacteria evolved from eukaryotes, but the difference with Senapathy is that Forterre does not claim that all eukaryotes arose independently. So although Forterre's view is highly unorthodox and implausible, Senapathy's view is a million times more unlikely.
64. Nick Lane (2005) Power, Sex, Suicide. Mitochondria and the Meaning of Life, p.143.
65. Asexual reproduction in animals is rare: the freshwater polyp Hydra reproduces by budding and some insects like aphids show life phases of quick multiplication through diploid eggs that form large, genetically identical clones. But in difficult times, even these animals reproduce sexually. (Christiane Nüsslein-Volhard, 2006, p.21).
66. Please note that the primordial pond illustration on the cover shows a turtle, a frog, a crab, a butterfly, a worm, a fern, but no mammal and no human being. Please note that the illustration suggest frogs develop directly from DNA, but in reality they develop from tadpoles. Similarly, butterflies develop from larva; pupa (not in water!).
67. Blowing In The Wind. Seeds & Fruits Dispersed By Wind. (a beautifully illustrated page about all kinds of seed dispersal).
68. Robert Shapiro (2007) 'A simpler Origin for Life', Scientific American, june 2007, page 28.
69. Alec Panchen (1993) Evolution, p.175.
70. Reduced fitness in individuals due to homozygous deleterious alleles is known as "inbreeding depression". See: Scott Freeman and Jon Herron (2007) 'Evolutionary Analysis', page 270. See also: "the analysis found more than 4 million variants between Venter's maternal and paternal chromosomes. This suggests that humans differ by 0.5%, not 0.1%, as suggested by earlier estimates." Jon Cohen (2007) Venter's Genome Sheds New Light on Human Variation, Science, 7 Sep 2007. On the other hand inbreeding (of dogs) can result in extremely long stretches of identical DNA common in different individuals of the same breed -millions of bases long compared to the typical tens of thousands of bases in humans. This is artificial selection with probably high costs (Science 21 September 2007). It is no accident that DNA of dog breeds are now investigated for genes for 18 diseases including four cancers, four inflammatory disorders, and three heart diseases.
71. Catherine Jessus & Olivier Haccard (2007) 'Fertilization: Calcium's double punch', Nature 449, 297-298 (20 September 2007).
72. David Beerling (2007) The Emerald Planet: How Plants Changed Earth's History, pp.180-183. There are regions on earth (Athi Plains in Kenya) were C₃ and C₄ plants coexist, so that would be the place for Senapathy's primordial pond!
73. See: Carl Woese (review).
74. Catherine Brady (2007) Elizabeth Blackburn and the Story of Telomeres: Deciphering the Ends of DNA, The MIT Press.
75. Erika Check Hayden (2008) 'Evolution: Scandal! Sex-starved and still surviving', Nature, 10 april 2008. " "Bdelloid rotifers reproduce entirely without males: females package a complete copy of their DNA into eggs that develop, sans fertilization, into the next generation. Asexual reproduction certainly isn't unheard of in the animal world: parasitic bacteria force some insects to reproduce without males and female sharks kept alone in captivity have surprised their keepers by giving birth to baby sharks."
76. Vaclav Smil Energy in Nature and Society, MIT Press: 2008. 512 pp. reviewed in Nature, 10 april 2008.
77. David A. Wheeler et al (2008) 'The complete genome of an individual by massively parallel DNA sequencing', Nature, 452, 872-876 (17 April 2008)
78. Elliott Sober (2008) Evidence and Evolution. The logic behind the science, p.116.
79. Erwan G. Roussel et al (2008) 'Extending the Sub-Sea-Floor Biosphere', Science, 23 May 2008.
80. For this amazing story see: Audubon Magazine. For a map see here. If the primordial pond is at sea level, do these geese survive at that level? How does the bizar migratory behaviour originate? Random? That's a helpful explanation! Senapathy never tells us when, and where the primordial pond existed!
81. In fact when one looks closely to the quote from page 204, Senapathy is describing random mutation followed by natural selection!!!
82. See for explanation 'Vicious circle' box in my review of Hubert Yockey. This is a devastating obstacle for Independent Origin for the same reason that any mutation in the tRNA genes is lethal. See also: 'Does life look unlike evolution?' in my review of Walter Remine.
83. "RNA nucleotides have never been synthesized from scratch, in spite of decades of focused effort" (Robert M. Hazen (2005) Genesis. The scientific quest for life's origin, p.219. Also: "Nucleotides, the building blocks of DNA have never been produced in any prebiotic synthesis experiment" (Barton, p.95). Senapathy can never solve this problem by supposing that nucleotides where synthesised under genome control, because without nucleotides no genomes!
84. But not impossible. It is quite funny that Senapathy did not claim that with enough time prokaryote genomes could originate.
85. Gordon Campbell in: M.R. Wright (2000) 'Reason and necessity'.
86. Pier Luigi Luisi (2006) The Emergence of Life. From chemcial origins to synthetic biology, page 208.
87. Sheref S. Mansy et al (2008) 'Template-directed synthesis of a genetic polymer in a model protocell', Nature, 3 Jul 2008.
88. "Neo-Darwinism is in fact falsifiable, for there are many empirically testable claims made, for example within modern genetics which currently explains the core principle of inheritance. However, if it were to be falsified a new theory would have to replace it, in order to explain design in a non-theological fashion, and this would have very many features in common with neo-Darwinism simply because of the explanatory burden such a theory would have to carry." Thomas E. Dickins in: Evolutionary Psychology, 2005. 3: 79-84. This is very interesting: not only any alternative to evolution needs to explain the same set of facts, it also is expected to have much in common with neo-Darwinism. This is exactly what Senapathy is doing: he copies natural selection and common descent into his theory!!! What he does not do is use the same set of data as neo-Darwinism. Furthermore, Intelligent Design theorist Michael Behe incorporates natural selection and common descent into his ID theory!
89. Nicholas H. Barton, Derek E.G. Briggs, Jonathan A. Eisen, David B. Goldstein, Nipam H. Patel (2007) Evolution, Cold Spring Harbor Laboratory Press, hardback 833 pp. (review).
90. See for the probability of the spontaneous origin of a well-designed body: Richard Dawkins (1991) The Blind Watchmaker, Penguin books 1991 paperback edition, page 146.
91. Additionally, meiotic recombination shuffles the genome, so each generation inherits a new combination of parental traits. How does Senapathy's theory explain the origin and continued existence of such a widespread, complex and costly proces as meiotic recombination? Meiotic recombination contradicts the idea that genomes are essentially fixed. What is the purpose of a recombination of parental genomes?
92. John Maynard Smith (1999) The Origin of Life, page 3.
93. John Maynard Smith (1995,1997) The Theory of Evolution, Cambridge University Press paperback. p.110.
94. I overlooked this figure and his claim that the primordial pond coincides with the Cambrian explosion. However, it only makes my argument stronger and clearer.
95. Senapathy appears to know that chromosomes occur in pairs. On pag 588 in note 109 he mentions homologous chromosomes. He even knows that one chromosome of a homologous pair of chromosomes is from the father, the other from the mother.
96. However, he seems to adopt an infinite universe of DNA sequences which does the trick for him.
97. Of the myriad problems of this scenario I mention a simple error: "Only those individuals with the absolutely right organs will survive" is not correct for reproductive organs! The situation is not analogous. One does not need sex organs to survive, while one does need hart, lungs, kidney, liver, mouth, teeth, stomach, intestines, and anus to survive. Infertile people don't die. See: 'The female and male genome' on this page.
98. A good overview is: chapter 17 in: Stephen Stearns and Rolf Hoekstra (2005), second edition.
99. page 8. This is a revealing and charming description of his naive way of thinking.
100. Daniel Fairbanks (2007) Relics of Eden. The powerful evidence of evolution in human DNA, p.154.
101. John Allman (2000) Evolving Brains, Scientific American Library, page 86
102. Dylan Chivian et al (2008) 'Environmental Genomics Reveals a Single-Species Ecosystem Deep Within Earth', Science 10 October 2008.
103. Science Daily (2003) Ultra-low Oxygen Could Have Triggered Die-offs, Spurred Bird Breathing System, Oct. 31, 2003.
104. Helen Pearson (2008) 'Outcry at scale of inheritance project', Nature, 10 October 2008
105. Periannan Senapathy et al (2008) 'Origination of the Split Structure of Spliceosomal Genes from Random Genetic Sequences', Plos One, October 20, 2008. Open Access.
106. When did this processing occur? Some evidence suggests that Senapathy means prebiotic processing, because he writes: "Stop codons occurred too frequently to allow functional proteins to be encoded in random DNA" (my emphasis). Life could not have started with too short genes and proteins, that would be incompatible with life. Life requires functional proteins. On the other hand, Senapathy also provides evidence that a substantial amount of processing occurred after the origin of random DNA: "The average exon length from the intron-rich genomes is about 170 bases whereas that expected from random ORF lengths is 60 bases. This may indicate that there has been a selection for longer exons within the allowed maximum ORF length of 600 bases for optimizing the frequency of suitable exon lengths." (my emphasis). Further evidence supports this interpretation: "mRNA splicing evolved to overcome the problem of the frequent occurrence of stop codons in primordial random DNA"; "RNA splicing evolved to circumvent the problem of short ORFs"; "According to the ROSG model, mRNA splicing evolved to overcome the problem of the frequent occurrence of stop codons in primordial random DNA that severely restricted ORF lengths." This is vague. Senapathy is not clear about it. A good scientific theory should be clear.
107. Computational Discovery of Internal Micro-Exons
108. Stewart Scherer (2008) A Short Guide to the Human Genome, p.32.
109. Ann Gibbons (2008) 'The Birth of Childhood', Science 14 November 2008.
110. Henry Nicholls (2008) 'Darwin 200: Let's make a mammoth', Nature 456, 310-314 (2008). Let's make a mammoth from its DNA is a perfect analogy with Senapathy's project to create an animal from its genome! All the problems and obstacles to create a mammoth from its DNA appear in Senapathy's scenario!
111. Organisms could do with only CG pairs or only AT pairs. Furthermore, it is chemically possible to have 3 different base pairs and 6 bases, or 4 base pairs and 8 bases, or 6 base pairs and 12 bases (Nicholas Barton et al (2007) Evolution, page 561). Information in DNA can still be coded with one base pair. Each strand would have a sequence such as GCCGGGGC..., and each amono acid could be coded by four or five bases instead of three. Replication with only one base pair would be most accurate because only G or C (say) would need to be distinguished.
112. In an interview Jerry Coyne says: "I don't know of any challenge to evolution that's ever come from a non-religious person. Personally I've never experienced one.". Senapathy is such a non-religious critic of evolution.
113. Noncoding DNA
114. Actually Carl Woese showed that 'Prokaryotes' must be replaced with 'Archaea' and 'Bacteria' or alternatively with 'microorganisms'. See also: Norman R. Pace (2009) 'It's time retire the prokaryote', Microbiology Today, May 2009, 85-87.
115. Kurland CG, Collins LJ, Penny D (2006) Science 312:1011-1014. Quoted by Lynch
116. John S. Mattick and Igor V. Makunin (2006) 'Non-coding RNA', Human Molecular Genetics 2006 15.
117. Eugene V. Koonin (2009) Darwinian evolution in the light of genomics, Nucleic Acids Research, 2009, Vol. 37, No. 4 1011-1034.
118. Henrik Kaessmann (2009) More Than Just a Copy, Science.
119. Carol Greider, Elizabeth Blackburn and Jack Szostak received the Nobel prize 2009 for their work on telemeres. Nature
120. Fuyuki Ishikawa and Taku Naito (1999) 'Why do we have linear chromosomes? A matter of Adam and Eve', Mutation Research/DNA Repair Volume 434, Issue 2, 23 June 1999, Pages 99-107: "Bacterial circular chromosomes have sporadically become linearised during prokaryote evolution".
121. Dirk Schübeler (2009) 'Epigenomics: Methylation matters' Nature 462, 296-297 (19 November 2009)
122. Dennis McCarthy (2009) Here be dragons. How the study of animal and plants distributions revolutionzied our views of life and Earth, p.100.
123. Dennis McCarthy (2009) 'Here be dragons', p.186 and 191.
124. See also: "As Simpson himself pointed out, -any event that is not absolutely impossible ... becomes probable if enough time elapses" (Nature, 4 Feb 2010) about Madagascar species. What we need is quantification.
125. Stewart Scherer (2008) A Short Guide to the Human Genome, p.41.
126. Explanation of basic principles: Reading the Genetic Code (Nature Education).
127. Michael Yarus (2010) Life from an RNA world, Harvard University Press.
128. This very profound objection to independent origin occured to me only 7 years after I started this review.
129. Elizabeth Pennisi (2010) 'Synthetic Genome Brings New Life to Bacterium', Science, 21 May 2010.
130. Douglas L. Theobald (2010) 'A formal test of the theory of universal common ancestry', Nature 465 219-222 (13 May 2010). But see: The common ancestry of life.
131. Nick Lane & William Martin (2010) 'The energetics of genome complexity', Nature, 467 929-934 21 October 2010
132. France Denoeud (2010) 'Plasticity of Animal Genome Architecture Unmasked by Rapid Evolution of a Pelagic Tunicate', Science, Published Online 18 November 2010.
133. Felisa A. Smith et al (2010) 'The Evolution of Maximum Body Size of Terrestrial Mammals', Science, 26 November 2010.
134. Elizabeth Pennisi (2010) Shining a Light on the Genome's 'Dark Matter', Science 17 dec 2010
135. 'meaningless/meaningful': is relative to the language. This also holds for the genetic code language! Senapathy would have found genes from an arbitrary genetic language in a random piece of computer DNA, because meaningful genes can be produced by any genetic language. The point is however, that in a computer experiment it's easy to use the same language during the experiment, while in natural experiments there is nothing that ensures the same genetic language during the production of even one genome, let alone all genomes.
136. O.B. Ptitsyn (1984) 'Random sequences and protein folding', Journal of Molecular Structure: THEOCHEM Volume 24, Issues 1-2, July 1985
137. V. S. Pande et al (1994) 'Nonrandomness in protein sequences: Evidence for a physically driven stage of evolution?' PNAS Vol. 91, pp. 12972-12975, December 1994.
138. Anthony D. Keefe & Jack W. Szostak (2001) 'Functional proteins from a random-sequence library', Nature 410, 715-718.
139. Codon usage in E. coli and: codon usage.
140. D M Raup and J W Valentine Multiple origins of life PNAS May 1, 1983 vol. 80 no. 10 2981-2984
141. Senapthy uploaded 3 papers to Nature Precedings (Documents on Nature Precedings are not peer-reviewed, but any visitor can comment):
     - Origin of biological information: Inherent occurrence of intron-rich split genes, coding for complex extant proteins, within pre-biotic random genetic sequences 13 December 2010 07:04
     - The inherent occurrence of complex intron-rich spliceosomal split genes, including regulatory and splicing elements, within pre-biotic random genetic sequences 13 December 2010 07:27
     - Parallel genome assembly from pre-biotic split-genes: A solution for the mosaic genome conundrum 13 December 2010 07:53
     I submitted 3 comments to the first document, but only one was posted. Remarkably, that comments are blocked while simultaneous submitting 3 large articles is no problem at all! Only later the second one appeared. And on 28 February 2011 Senapathy replied.
142. T. Mourier and D. C. Jeffares (2003) 'Eukaryotic Intron Loss', Science p.1393, 30 May 2003.
143. Sakharkar KR (2006) 'Functional and evolutionary analyses on expressed intronless genes in the mouse genome', FEBS Lett. 2006 Feb 20;580(5):1472-8. Epub 2006 Jan 31.
144. Jain M et al (2008) 'Genome-wide analysis of intronless genes in rice and Arabidopsis', Funct Integr Genomics. 2008 Feb;8(1):69-78. Epub 2007 Jun 20.
145. Syozo Osawa (1995) Evolution of the Genetic Code, Oxford University Press. page 150.
146. Dmitry V. Fyodorov & James T. Kadonaga (2002) 'Dynamics of ATP-dependent chromatin assembly by ACF', Nature 418, 896-900 (22 August 2002)
147. C. G. Kurland, L. J. Collins, D. Penny (2006) Genomics and the Irreducible Nature of Eukaryote Cells, Science 19 May 2006
148. T. M. Embley, W. Martin (2006) 'Eukaryotic evolution, changes and challenges', Nature 440, 623 (Mar 30, 2006):
     "In recent years, even that has been called into question, as some phylogenies have suggested that prokaryotes might be derived from eukaryotes".
149. Eugene V. Koonin (2009) 'Intron-Dominated Genomes of Early Ancestors of Eukaryotes', J Hered (2009) 100 (5): 618-623.
150. N. H. Barton et al (2007) Evolution, Cold Spring Harbor Laboratory Press, p.220.
151. Group I catalytic intron in wikipedia. Homing endonuclease recognition sequences are long enough to occur randomly only with a very low probability: approximately once every 7×10¹⁰ bp.
152. Scott William Roy, Walter Gilbert (2006) The evolution of spliceosomal introns: patterns, puzzles and progress, Nature Reviews Genetics Volume 7 March 2006 211
153. Francisco Rodríguez-Trelles, Rosa Tarrío, Francisco J. Ayala (2006) 'Origins and Evolution of Spliceosomal Introns', Annu. Rev. Genet. 2006. 40:47-76. Very imporant article (introns-first hypothesis).
154. Sequence and organization of the human mitochondrial genome, Nature (1981) 290: 457-65. Also: The mouse mitochondrial genome displays exceptional economy of organization, protein-coding genes with zero or few noncoding nucleotides between coding sequences .
155. Lawrence A. David, Eric J. Alm (2011) 'Rapid evolutionary innovation during an Archaean genetic expansion', Nature, 469, 93-96. 06 January 2011
156. GenScript (accessed 6 Jan 2011)
157. "Our findings thus show that any split gene that can encode complex proteins which form the structure of the spliceosome or any other eukaryotic cellular organelle," (p.8). This equals to the claim that organelles were designed.
158. Brian Hall, Benedikt Hallgrimsson (2008) Strickberger's Evolution, Fourth edition, page 139.
159. Lee R. Kump (2010) 'Earth's Second Wind', Science 10 December 2010
160. Radu Popa (2004) Between Necessity and Probability: Searching for the Definition and Origin of Life, Springer, p. 67-68.
161. In previous versions I stated only that every OOL theory needs to explain the restricted choice of the genetic code in the face of the huge freedom of choice, but later I realised that precisely this freedom of choice forces any theory of independent origin to predict a huge diversity of genetic codes (11 Jan 11).
162. "The non-universal genetic codes are not produced randomly, but are derived from the universal genetic code as the result of a series of non-disruptive changes" (Syozo Osawa (1995) 'Evolution of the Genetic Code', p.171). Senapathy's theory would predict that non-universal codes are (1) random, (2) ubiquitous, (3) originated in the beginning. All predictions are wrong.
163. Michael Lynch (2002) 'Intron evolution as a population-genetic process', Proc Natl Acad Sci U S A. 2002 April 30.
164. Michael Lynch, John S. Conery (2003) 'The Origins of Genome Complexity', Science 302 21 Nov 2003.
165. Eugene V Koonin (2006) 'The origin of introns and their role in eukaryogenesis: a compromise solution to the introns-early versus introns-late debate?', Biology Direct. Koonin seems to be a little bit genome-centered too! (with response from Ford Doolittle).
166. D. Fridmanis et al (2007) 'Formation of new genes explains lower intron density in mammalian Rhodopsin G protein-coupled receptors', Mol Phylogenet Evol. 2007 Jun; 43(3):864-80.
167. Tom Strachan, Andrew Read (2000) Human Molecular Genetics Second Edition, p.150-152.
168. Sarah Blaffer Hrdy (2009) Mothers and Others, p. 101.
169. JE Darnell, Jr (1978) Implications of RNA-RNA splicing in evolution of eukaryotic cells, Science 22 December 1978:
     Abstract: "The differences in the biochemistry of messenger RNA formation in eukaryotes compared to prokaryotes are so profound as to suggest that sequential prokaryotic to eukaryotic cell evolution seems unlikely. The recently discovered noncontiguous sequences in eukaryotic DNA that encode messenger RNA may reflect an ancient, rather than a new, distribution of information in DNA and that eukaryotes evolved independently of prokaryotes."
     
170. Martin and Koonin (2006) Introns and the origin of nucleus-cytosol compartmentalization, Nature 440, 41-45 (2 March 2006)
171. Daniel C. Jeffares, Tobias Mourier, David Penny (2006) 'The biology of intron gain and loss', TRENDS in Genetics Vol.22 No.1 January 2006
172. In theory Senapathy could argue that prokaryotes originated independently and had as many introns as eukaryotes but lost them completely, since several publications argue that clear instances of massive intron loss make the case for complete intron loss in prokaryotes plausible. This implies strong Darwinian selection.
173. Anthony Poole, Daniel Jeffares, David Penny (1999) Early evolution: prokaryotes, the new kids on the block, BioEssays 21:880-889, 1999.
174. Morgan Ryan (2011) Unauthorized reproduction not prohibited, American Scientist, Vol 99, p. 30.
175. M.B. Shapiro, P. Senapathy (1987) "RNA splice junctions of different classes of eukaryotes" is cited in: László Patthy (1999) Protein Evolution, p. 148.
176. Monya Baker (2011) 'Genomics: Genomes in three dimensions', Nature, 470, 289-294 (10 February 2011)
177. Tom Misteli (2007) Beyond the Sequence: Cellular Organization of Genome Function, Cell 128, 787-800, February 23, 2007
178. Tom Misteli (2011) The Inner Life of the Genome Scientific American Feb 2011.
179. Dan Graur, W H Li (2000) Fundamentals of Molecular Evolution, p.289 and 296.
180. Guy M. Narbonne (2011) Evolutionary biology: When life got big, Nature 470, 17 February 2011
181. Eddo Kim (2007) Different levels of alternative splicing among eukaryotes, Nucleic Acids Res. 2007 January; 35(1): 125-131.
182. Aubrey E. Hill, Eric J. Sorscher (2006) The non-random distribution of intronless human genes across molecular function categories, FEBS Letters.
183. Ribozymes.
184. Francis Crick (1981) Life Itself. It's Origin and Nature, Simon and Schuster.
185. Monroe Strickberger (2000) Evolution, Third edition, p.143.
186. Michael IP (2005) Intron retention: a common splicing event within the human kallikrein gene family. Clin Chem. 2005 Mar;51(3):506-15.
187. Gene Splicing Overview & Techniques.
188. Andreas Wagner (2005) Energy Constraints on the Evolution of Gene Expression, Molecular Biology and Evolution, 22, 6 Pp. 1365-1374
189. Ner-Gaon H (2004) Intron retention is a major phenomenon in alternative splicing in Arabidopsis, Plant J. 2004 Sep;39(6):877-85.
190. Knowles DG, 2. McLysaght A (2009) Recent de novo origin of human protein-coding genes. Genome Research
191. Maren Krull, Jürgen Brosius and Jürgen Schmitz (2005) Alu-SINE Exonization: En Route to Protein-Coding Function, Molecular Biology and Evolution 22, 8 1702-1711
192. Manfred Eigen (1992) Steps towards Life. A perspective on Evolution, Oxford University Press. (paperback edition: 1996) See also wikipedia article Error threshold.
193. Richard Dawkins (1986) The Blind Watchmaker, chapter 3.
194. P Senapathy (1986) Origin of eukaryotic introns: a hypothesis, based on codon distribution statistics in genes, and its implications, PNAS April 1, 1986 vol. 83 no. 7 2133-2137. The abstract is a beautiful succinct summary (written 8 years before his book) of his whole theory!
195. Francesco Catania, Xiang Gao and Douglas G. Scofield Endogenous Mechanisms for the Origins of Spliceosomal Introns, J Hered (2009) 100 (5): 591-596. Quote: "Spliceosomal introns have also been suggested to directly arise from random primordial and canonical ancestral gene sequences (the 'split-gene model' and the 'proto-splice site model', respectively). In particular, Senapathy (1986)". Further Senapathy (1986) is quoted in: Masaru Tomita et al (1996) 'Introns and Reading Frames: Correlation Between Splicing Sites and Their Codon Positions', Mol. Biol. Evol. 13(9):1219-1223.
196. Lewin's GENES X, 2011, p. 86.
197. Donald R. Forsdyke & James R. Mortimer (2000) Chargaff's legacy, Gene (2000) 261, 127-137
198. Cory Y. McLean et al (2011) Human-specific loss of regulatory DNA and the evolution of human-specific traits, Nature 10 Mar 2011
199. Manyuan Long and Carl Rosenberg (2000) Testing the 'Proto-splice Sites' Model of Intron Origin: Evidence from Analysis of Intron Phase Correlations, Mol Biol Evol (2000) 17 (12): 1789-1796. Another way of measuring intron phases is expressing exon length as multiples of 3, 3N+1, 3N+2.
200. Compare with W F Doolittle: 'Genes in pieces: Were they ever together?' Nature 1978, 272:581-582.
201. Jeffrey M. Perkel (2011) Synthetic Genomes: Building a better Bacterium, Science, 25 Mar 2011
202. See my review of Information theory and molecular biology by Hubert Yockey.
203. Eileen E. M. Furlong (2011) Molecular biology: A fly in the face of genomics, Nature 471, 458-459 24 March 2011
204. S Ragsdale (2011) Biochemistry: How two amino acids become one, Nature, 31 Mar 2011 shows that the stopcodon UAG from methanogenic Archaea encodes the new amino acid Pyrrolysine. So it only has two stopcodons. Tetrahymena species recognize only UGA as a stop codon, while Euplotes species recognize only UAA and UAG as stop codons (Joe Salas-Marco et al, 2006).
205. Ryan E. Mills et all (2011) 'Natural genetic variation caused by small insertions and deletions in the human genome', Genome Research April 1, 2011
206. Gretchen Vogel (2011) 'Do Jumping Genes Spawn Diversity?, Science, 15 April 2011.
207. Jevon Plunkett et al (2011) An Evolutionary Genomic Approach to Identify Genes Involved in Human Birth Timing, PLoS Genetics April 2011
208. Kevin Plaxco and Michael Gross (2006) Astrobiology. A Brief Introduction, page 71: "These amino acids were almost certainly introduced by biochemistry after the origins of life".
209. Hadas Keren, Galit Lev-Maor & Gil Ast (2010) Alternative splicing and evolution: diversification, exon definition and function, Nature Review Genetics, 11, 345-355 (May 2010)
210. Elizabeth Pennisi (2011) 'Green Genomes', Science 17 Jun 2011
211. "It is worth noting that the average length of metazoan exons (125 - 165 bp) is similar to the length of DNA that wraps around a nucleosome (147 bp), which suggests that nucleosome occupancy might confer purifying selection on exon length. However, the length of an average human exon is only 126 bp." From ref 209.
212. Elçin Ünal et all (2011) Gametogenesis Eliminates Age-Induced Cellular Damage and Resets Life Span in Yeast, Science, 24 Jun 2011.
213. "The oceans are teeming with viruses — typically, there are 100 billion viral particles per litre of water in the top 50 metres of most marine ecosystems. With an average of ten viruses for each bacterial cell, these parasites impose a tight control over the composition of marine microbial communities. The 'arms race' hypothesis holds that the selective pressure exerted by viruses continuously triggers adaptive mutations in the bacterial genomes, with counteracting genetic adaptations occurring at a similar pace in the parasites." Science 30 jun 2011.
214. Mingyao Li et al (2011) Widespread RNA and DNA Sequence Differences in the Human Transcriptome, Science, 1 Jul 2011 :"We have uncovered thousands of exonic sites where the RNA sequences do not match those of the DNA sequences, including transitions [changes a purine nucleotide to another purine] and transversions [substitution of a purine for a pyrimidine or vice versa]".
215. David Deamer (2011) First Life. Discovering the Connections between Stars, cells, and How Life Began. University of California Press, p. 183.
216. Denis Noble (2006) The Music of Life. Biology Beyond the Genome, Oxford University Press. See my short description on the Introduction page. The first four chapters are the most important, they explain what is wrong with genetic determinism.
217. See: David Deamer (note 215) page 214: "Can genetic information really appear out of nowhere, by chance?" where he reports the experiments of Bartel and Szostak (1993) "Isolation of new ribozymes from a large pool of random sequences', who began by synthetizing many trillions of different random RNA molecules 300 nucleotides long and found RNAs with catalytic activity. Furthermore, selection and amplification are involved, which are absent from Senapathy's scenario. Deamer concludes "The inescapable conclusion is that genetic information can appear out of random mixtures, as long as there are populations containing large numbers of polymeric molecules with variable sequences of monomers and a way to select and amplify specific property" (p.216). The conditions in this claim are extremely important! The problem here is: how do you get long polymeres in the first place? Long enough to be of catalytic value?
218. Warm and Cold-Blooded
219. The Central Dogma of molecular biology certainly reinforces genetic determinism because the direction of the flow of information is from DNA to RNA to proteins. This strongly suggests DNA is in control and there is no feedback.
220. Which came first, the bird or the smaller genome? 30 August 2007
221. Craig B. Lowe et al (2011) Three Periods of Regulatory Innovation During Vertebrate Evolution, Science, 19 August 2011.
222. A story of chromosome number, Nature 477, 9 1 September 2011
223. Y. Jiao et al (2011) Ancestral polyploidy in seed plants and angiosperms. Nature 473, 97 (2011).
224. T. E. Wood et al (2009) The frequency of polyploid speciation in vascular plants. Proc. Natl. Acad. Sci. U.S.A. 106, 13875 (2009).
225. Steven A. Frank (2009) Somatic evolutionary genomics: Mutations during development cause highly variable genetic mosaicism with risk of cancer and neurodegeneration, PNAS January 26, 2010 vol. 107
226. Centrosome (24 Sep 2011)
227. Kyle Vogan (2011) Maternal imprinting defect, Nature Genetics 43, 928
228. James Darnell (2011) RNA. Life's Indispensable molecule, p. 243.
229. Senapathy knows about the existence of the spliceosome in the Genetics Primer (p. 547, 555), although it does not occur in the index.
230. Evolution of nested gene arrangements, the ruvinsky lab.
231. Chun-Long Chen et al (2008) Genomewide Analysis of Box C/D and Box H/ACA snoRNAs in Chlamydomonas reinhardtii Reveals an Extensive Organization Into Intronic Gene Clusters, Genetics May 2008 vol. 179 no. 1 21-30.
232. Michael B. Clark et al (2011) The Reality of Pervasive Transcription PLoS Biology July 2011.
233. Eugene V Koonin, Tatiana G Senkevich, Valerian V Dolja (2006) 'The ancient Virus World and evolution of cells', Biology Direct 2006, 1:29. The authors use the words: "the primordial pool of primitive genetic elements"; "the primordial genetic pool", "The primordial gene pool", and "existence of a complex, precellular, compartmentalized but extensively mixing and recombining pool of genes"; "viral origin from the primordial genetic pool". However, "In this pool, RNA viruses would evolve first, followed by retroid elements, and DNA viruses.". So that is different from Senapathy: he starts with complete eukaryotic genomes. (I need to investigate this important publication! It seems that the authors make the mistake of 'protein-coding genes' without transcription and translation machinery!)
234. Stephen J. Freeland, et all (1999) Early Fixation of an Optimal Genetic Code, Mol Biol Evol (2000) 17 (4): 511-518.
235. A. D. Ellington (2009) Evolutionary origins and directed evolution of RNA, Int J Biochem Cell Biol. 2009 Feb;41(2):254-65. (See also Stuart A. Kauffman about random DNA libraries)
236. "A long explanation for introns", New Scientist, June 26, 1986 (see google books); "Exon, introns, and evolution", New Scientist, March 31, 1988 (see google books).
237. Martin Ackermann, Lin Chao (2006) DNA Sequences Shaped by Selection for Stability, PLoS Genetics, February 2006.
238. Woese, C. R. On the evolution of the genetic code. Proc. Natl Acad. Sci. USA 54, 1546–1552 (1965).
239. Tobias Warnecke, Laurence D. Hurst (2011) Error prevention and mitigation as forces in the evolution of genes and genomes, Nature Reviews Genetics 12, 875-881 (December 2011)
240. Brian P. Cusack, Peter F. Arndt, Laurent Duret, Hugues Roest Crollius (2011) Preventing Dangerous Nonsense: Selection for Robustness to Transcriptional Error in Human Genes, PLoS Genetics October 2011
241. Miodrag Grbic et al (2011) The genome of Tetranychus urticae reveals herbivorous pest adaptations, Nature 479, 487–492 (24 November 2011) Supplementary information Figure S2.4.2.
242. Richard Cordaux, Mark A. Batze (2009) The impact of retrotransposons on human genome evolution, Nature Reviews Genetics 10, 691-703 (October 2009) is a very usefull overview.
243. Erez Lieberman Aiden (2011) Zoom! Science 2 December 2011
244. William A. Wells (2005) There's DNA in those organelles, The Journal of Cell Biology, March 14 2005
245. Hans Ris and Walter Plaut (1962) Ultrastructure Of DNA-Containing Areas In The Chloroplast Of Chlamydomonas, The Journal of Cell Biology, 1 Jun 1962.
246. Eugene V. Koonin (2011) The Logic of Chance. Pearson Education, hardback.
247. Kevin N. Laland, Kim Sterelny, John Odling-Smee, William Hoppitt, Tobias Uller (2011) 'Cause and Effect in Biology Revisited: Is Mayr's Proximate-Ultimate Dichotomy Still Useful?', Science 16 Dec 2011.
248. RM Schwartz and MO Dayhoff (1978) 'Origins of prokaryotes, eukaryotes, mitochondria, and chloroplasts', Science 27 January 1978: 395-403.
249. Structure of the Mitochondrial Genome, Genetic Origins website.
250. "Translation in Escherichia requires the coordinated and complex interactions of at least 100 gene products." from: Ravi Jain, Maria C. Rivera, and James A. Lake (1999)Horizontal gene transfer among genomes: The complexity hypothesis, Proc. Natl. Acad. Sci. USA Vol. 96, pp. 3801–3806, March 1999
251. Stuart A. Kauffman (2011) Approaches to the Origin of Life on Earth, Life 2011, 1, 34-48 (Open Access)
252. Joan A. Steitz (2012) RNA Rejoice! Review of RNA Life's Indispensable Molecule by James Darnell, Science 6 January 2012
253. Ming Zou, Baocheng Guo, Shunping He (2011) 'The Roles and Evolutionary Patterns of Intronless Genes in Deuterostomes', Comparative and Functional Genomics, Volume 2011.
254. Brian K. Hall, Benedict Hallgrimsson (2008) Strickberger's Evolution Fourth Edition, p. 134.
255. Dennis W. Grogan (2002) Hyperthermophiles and the problem of DNA instability, Molecular Microbiology.
256. Scott Freeman and Jon Herron (2007) 'Evolutionary Analysis', page 657.
257. Martin Egli (2006) Uncovering DNA's 'sweet' secret. One particular curiosity: how did DNA and RNA come to incorporate five-carbon sugars into their "backbone" when six-carbon sugars, like glucose, may have been more common?
258. Miklos Csuros, Igor B. Rogozin, Eugene V. Koonin (2011) A Detailed History of Intron-rich Eukaryotic Ancestors Inferred from a Global Survey of 100 Complete Genomes, PLoS Computational Biology September 2011.
259. Igor B. Rogozin, Yuri I. Wolf, Alexander V. Sorokin, Boris G. Mirkin, and Eugene V. Koonin, (2003) Remarkable Interkingdom Conservation of Intron Positions and Massive, Lineage-Specific Intron Loss and Gain in Eukaryotic Evolution, Current Biology, Vol. 13, 1512–1517, September 2, 2003.
260. NCBI The RNA World and the Origins of Life.
261. Lindberg J, Lundeberg J. (2009) The plasticity of the mammalian transcriptome, Genomics 2010 Jan;95(1):1-6.
262. Furthermore, E. Koonin notes that the emergence of spurious (weak) transcription initiation sites in random DNA sequences is relatively easy (given the existence of Transcription factors of course) (p. 240, Note 246).
263. Aaron E. Engelhart and Nicholas V. Hud (2010) Primitive Genetic Polymers, Cold Spring Harbor Perspectives in Biology, 12 May 2010.
264. Aaron Klug (2004) 'The Discovery of the DNA Double Helix', Journal of Molecular Biology, Volume 335, Issue 1, 2 January 2004, Pages 3-26 (available as: klug-DNA.pdf)
265. The standard laboratory technique to isolate DNA includes digestion with proteinase which removes all proteins (histones).
266. How Many People Have Ever Lived On Earth? Population reference Bureau, assessed 9 Feb 2012.
267. Monya Baker (2012) Functional genomics: The changes that count, Nature 482, 257–262 09 February 2012
268. Kerstin Lindblad-Toh et al (2011) A high-resolution map of human evolutionary constraint using 29 mammals, Nature 478, 476–482 (27 October 2011)

• Periannan Senapathy's company Genome Technologies.
• Senapathy's new home site.
• Senapathy's immodest autobiography.
• Independent Birth of Organisms - A New Theory That Distinct Organisms Arose Independenlty From the Primordial Pond Showing That Evolutionary Theories Are Fundamentally Incorrect (1994). Genome Press, Madison, 635 pages. The book is free available as an Adobe pdf file (3 MB!). Fast internet connection recommended. The pdf file is full-text searchable, which is extremely handy for research purposes (recommended for any book! Each book should also be published on CDROM!)
• Here is a list of publications of Senapathy P (Periannan) from the BioInfoBank Library. More on p.598 of his book. Please note that peer-reviewed journals are included in the list, but as far as I can see from the abstracts those publications do not mention his theory of independent origin of organisms!
• PRWEB Genome Data Proves False the Theory of Evolution, New Theory Shows Complex Animals and Plants Originated from Prebiotic Chemistry, December 15, 2010
• A layman's summary of the new theory by Jeffrey Mattox. With many links (some dead links). Mattox is an electrical engineer who discovered Senapathy.
• Double helix: 50 years of DNA (from Nature), containing a collection of overviews celebrating the historical, scientific and cultural impacts of the discovery of the double helix. All content is free.
• Gert Korthof: A Chemist's View of Life: Ultimate Reductionism & Dissent. A review of Schwabe's book
• Gert Korthof: Independent Origin and the facts of life. Reasons from developmental biology, genetics and ecology (please note that I skipped reasons from evolution biology!)
• Gert Korthof: a review of The principles of Life by Tibor Gánti. (the origin of life)
• Gert Korthof: a review of Lynn Margulis and Dorion Sagan (2002) Acquiring Genomes. A theory of the origin of species. Recommended reading. If anything contradicts independent origin then it is Margulis' now well established symbiosis theory.
• Gert Korthof: The Feathered Onion is a review of Clive Trotman's book. Summary: Is the time span for the origin of life on earth too short?
• How Many New Genes Are There? Science Vol 311 24 March 2006 1709. This article uses computer generated random (intron-free) cDNA sequences of 2000 bases in length and concluded that by chance 1247 of 20,000 (6,2%) contain Open Reading Frames which could produce proteins of 119 or more amino acids.
• Robert M. Hazen, Patrick L. Griffin, James M. Carothers, and Jack W. Szostak (2007) 'Functional information and the emergence of biocomplexity', PNAS published online May 9, 2007. "Here we explore the functional information of randomly generated populations of Avida organisms." That is random genomes are generated! This would be a modest but careful way to explore genomespace and the probability of random generation of a funtional genome.
• Periannan Senapathy et al (2008) 'Origination of the Split Structure of Spliceosomal Genes from Random Genetic Sequences', Plos One, October 20, 2008. Open Access. ("and that a machinery was required for removing the genetic waste.": the concept 'genetic waste' has only meaning if a functional genome exist. Similarly, 'stop codon' only has meaning if the genetic code is already established.) Please note that the book reviewed on this page is present in the PLOS article as note 36, but the subtitle 'A New Theory That Distinct Organisms Arose Independently From The Primordial Pond Showing That Evolutionary Theories Are Fundamentally Incorrect' is omitted.
• T. Ryan Gregory and Niles Eldredge (2008) Spore biology. Surprisingly, this page is usefull for Senapathy supporters, because Senapathy's theory is like Spore Biology (need to elaborate this).

• Gert Korthof (2011) Senapathy publiceert in Nature Precedings, on korthof.blogspot.com 7 Jan 2011.