Senapathy Q & A Number 2

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From Periannan Senapathy
Date May 1995

I apologize for the long delay in drafting and posting this next set of replies. I run a small company that develops computational algorithms and software for genome-related research, and we were working against some tight deadlines. I have again prepared a comprehensive reply to all the relevant questions that have appeared in various forums regarding my new theory on the origin of life and organisms.

From Keith Robison in

>Senapathy's book expounding his theory of organismal emergence contains many incorrect statements about evolution, and many logical leaps which are undermined by available data. ....

>At the heart of this theory, though, is a hypothesis on the formation of genes which was published in the Proceedings of the National Academy of Sciences.

>What is this theory? It involves the probability of finding contiguous open reading frames (ORFs) in DNA versus the probability of finding them if one can splice regions together. In brief, Senapathy looks at the length of ORFs in DNA and pronounces it impossible to find gene-sized pieces this way. This is due to the expected distribution of ORF lengths (the waiting-interval between stop codons -- i.e. how many codons can you read before you hit another stop). But, he claims, if we can piece together shorter ORFs (via RNA splicing) we can make gene-sized ORFs.

>We can see the gaping flaw in Senapathy's logic quite simply in one of his examples. He shows how the sentence

    To be or not to be
>can be found in a block of random characters, if you skip nonsense and read only the words. But he was looking for that particular sentence. To properly apply his strategy, you must read EVERY English word which appears (after all, he is very fond of pointing out that selection can't occur until after a product is made). The following sentence is what I dredged out (I quite possibly missed some words):
    To awry hen
    be wet
    or wag bun kit kit
    not wed dew fed
    to set fed lop
>Not exactly the Bard, eh? (though it does have a certain rhythm...)

Keith Robison has again shown that he has not read the book fully, and has wholly missed the point about the extremely high probability of split-genes in random primordial sequences. As I have already explained, the probability of fully formed split- genes in random primordial DNA sequences is very high, no matter whether a gene contains only a few exons or as many as 100 or more exons. This is precisely the explanatory power of the new theory of the origin of split-genes: that due to many phenomena such as the codon-degeneracy in coding sequences, amino acid degeneracy in proteins, the high variability of sequences within the splice junctions, and the limitation in the length of exons to an upper limit of about 600 nucleotide characters (with only extremely rare exceptions), fully formed genes for fully functional proteins are highly probable within random DNA sequences that can be reasonably expected to occur within a small primordial pond. I have fully explained these phenomena and demonstrated how split-genes are highly probable in random primordial DNA sequences in my book (Chapter 7), and see no reason to repeat the argument here. The examples given are fully valid, showing that if we take exons in genes as words in a sentence, and ignore the intervening random characters as introns, a whole sentence is highly probable in a reasonably short random sequence.

>There is an additional level of complexity to this analysis which Senapathy conveniently ignores -- exons come in more than one flavor. Because the genetic code is read in sets of 3 (codons), the beginning of an exon has 3 possible alignments with the codons, and the end of an exon has 3 possible alignments. The beginning of codon exon N+1 must supply the missing bases in the last codon of exon N. I.e., if exon N ends on the first base of a codon, then exon N+1 must start with the second base of the codon. Known exons contain a mix of such flavors (called phases). The real waiting interval of interest here is the interval until the next usable splicing site -- not the next ORF (Senapathy essentially tries to equate these). In random DNA, 2/3 of the time simply picking two adjacent splice sites will result in a useless docking of exons. While it is perhaps plausible for genes with a few exons to show up randomly by this process, many genes contain 10-20 exons (and the current record is in the neighborhood of 100).

Keith is incorrect in his claim that my theory contains inconsistencies regarding the ORFs. In fact he has totally misunderstood it, because he has obviously not read the material concerning it. Contrary to his belief that I am ignorant of the ORFs and the exons being N, N+1 and N+2 nucleotide long where N is divisible by 3, I have extensively analyzed the ORF phases and have developed algorithms for finding exons of a gene. (See Shapiro & Senapathy, "RNA Splice junctions of different classes of eukaryotes: Sequence statistics and functional implications in gene-expression," 1987, Nucleic Acids Research, 15:7155-7175; and Senapathy et al, "Splice junctions, branch point sites, and exons: Sequence statistics, Identification, and Applications to the Genome Project," in Methods in Enzymology, Computer analysis of Protein and Nucleic Acid Sequences, Doolittle, R. F. ed., 183:252- 278.)

>It is interesting to note here an inconsistency in Senapathy's book -- the frequency/specificity of splice sites in DNA closely follows the needs of the argument at hand. When he is arguing that it is probable to find genes in random sequence data, then just about every stop codon is a working splice site (otherwise, his proto-exons would be much rarer; many long ORFs would not be spliceable). When he needs to explain away large introns (more than a few are 100Kb-1000Kb in length), they are suddenly rare and highly-specific.

Keith has missed completely my explanation as to how fully-formed genes can occur within totally random primordial sequences. If we look for only exons of a gene in a random DNA sequence, and skip the random DNA sequences between the consecutively occurring exons, we are certain to find the complete gene within lengths that are realistic (meaning that the length of the gene that we so find will be comparable to the lengths of genes that we find today in living organisms). In doing so, we do start with the complete sequence of a given protein (with all its known amino acid degeneracy). The underlying idea is that, within a finite quantity of random primordial DNA in a primordial pond, we should be able to find all the genes that are needed for constructing the genomes of all organisms that we find on earth. In other words, we can find a gene for almost any protein function within the finite random DNA sequences. Under these circumstances, it is completely valid to look for a particular gene's occurrence within the finite random sequence. The example taken in the book is one of such any genes. This is the reason for looking for the given words of the given gene.

The book explains with clear examples how the fully-formed split- gene for a protein with almost any biochemical function we can think of can occur within the finite amount of random primordial DNA sequence. I show that a finite amount of random DNA sequences totaling 10^26 nucleotides is the approximate quantity for fully- formed genes to occur. In this amount, billions of distinct genes for distinct biochemical functions can occur, with precisely all the structural features that the genes of all living multicellular organisms exhibit today. This can be demonstrated by computer simulations that incorporate all the structural features of the genes of living organisms, and this is precisely what I have done in Chapter 7 of my book.

In this context it should be noted that there are only three competing theories as to how genes have originated on earth.

Keith Robison wrote in

>Senapathy argues quite forcefully that the mutations required to change one genome into another are simply not possible: that at measured mutation rates not enough time could ever pass to change an extended region of DNA by even a small amount (say 10-20%). Rather than trying to argue how mutations fix or at what rate, we can go to some data. Suppose we look at fruit flies. There are many species of fruit flies, and even Senapathy's theory would claim that they have a common ancestor. Drosophila melanogaster and D.virilis are two fruit flies, and we can compare the DNA sequences between them. Strikingly, what is found is that most sequences which do NOT code for protein or RNA show essentially no resemblance to each other. In other words, an impossible (according to Senapathy) number of mutations has occurred! Since the data is real, there must be a flaw in the logic which declares this impossible.

Yes! I do argue quite forcefully that mutations required to change the genome of one distinct organism into that of another distinct organism are simply not possible. Now, what Keith proposes is that we simply ignore all that we have learned about mutation rates and come to some data, which is in fact pointed by a special case. The example of the Drosophila is probably caused by a transposon element such as the P elements, which are known to cause drastic changes within the genome, but without changing the coding regions of the genes. This phenomenon is known as "Hybrid Dysgenesis," which phenomenon cannot contribute anything to evolution. I have described this phenomenon in my book (pages 116-117 in Chapter 4). I am fully aware of questions such as these, and that is why I have made a point of addressing such special cases in my book, demonstrating how even these cases cannot be contributors to evolution, as molecular evolutionists simply assume. The most important thing that should be taken into account is the fact that none of the genes' coding sequences within the Drosophila's genome has been changed by this phenomenon. My premise that no mutation will change the constancy of the genes and the fixity of the genome's developmental genetic network is borne out to be true here.

In essence what Keith says here is that "Senapathy says that mutation rate is limited, but see here in this case of fruit flies, there is a great deal of mutation within the non-coding regions." But can Keith answer this question: After the great many number of mutations did the organism Drosophila change into another organism? No! It remained the very same organism, and changed only to a very similar species. With these many mutations, did the coding regions of genes (i.e. the proteins) change into new proteins? No, they did not.

>Senapathy claims that the taxon "Mammalia" is an artificial grouping of independently derived lines. While he isn't specific about how many independent lines, he explicitly claims that monotremes (egg-layers), marsupials, and eutherians (placental) mammals are independent. If we look at the chromosomes of mammals, we see that there is a great degree of synteny (conserved chromosomal ordering of genes). Furthermore, it is likely that some of this synteny extends beyond the mammals and into other vertebrates.

>Why do biologists care about all this? Because it leads to useful hypotheses. For example, Senapathy basically claims that cloning genes by sequence similarity is a fad and not inherently informative. I offer in contrast

>Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes Aparicio et al. Proc Natl Acad Sci U.S.A. 1684-1688 (1995)

>Aparicio et al cloned a hox-type developmental gene from Fugu, the notorious Japanese delicacy. Comparison of the upstream non-coding regions revealed a few islands of sequence similarity. Transgenes containing these segments were put into mice, and the segments directed specific expression of reporter constructs in mice. In other words, sequence similarity implied functional similarity, which was demonstrated in vivo. The underlying logic behind this is that the entire system (sites, Hox gene, DNA binding protein) in both organisms has a common origin. There is no particular reason to expect these results given Senapathy's hypothesis -- there are thousands of possible recognition sequences for transcription factors, and no particular reason that Mouse Hox and Fugu Hox should use the same ones.

I have discussed at length how homeobox genes can be used as common reagents in the development of distinct and unrelated organisms by the inclusion of such genes in distinct genomes being assembled from a common pool of genes. I have also gone into detail as to how the homeoboxes are short DNA sequences and their probabilities are high, and how sequence similarity leading to functional similarity can arise in totally independent random sequences in the primordial pond. It is very important to note that in the homeobox containing proteins, only the homeodomain (which are short) are similar, and the other long regions of proteins (other domains) are very distinct.

Again, as I have said before, my theory does accommodate the molecular synteny among groups of organisms. My theory says that during the independent assembly of genomes from a common pool of genes in the primordial pond, genome mixing can occur, once the genomes started to form. Also, once the genomes were being formed, they could change into slightly changed genomes and could give rise to changed organisms, but with similar genomes. This phenomenon of genomic repatterning and restructuring, and mixing between distinct genomes could lead to distinctly new genomes but with large portions common to the different resulting genomes. Please note that all these processes could have happened within a small primordial pond, like in a closed vessel. This will lead to organisms that were independently arising from the otherwise independently assembled genomes, but which can have varying degrees of chromosomal synteny. This fits well with the fact that all these organisms appear fully formed in the fossil record, and the fact that they have never changed from their original state of appearance in the fossil record until today.

From Keith Robison in (who begins by quoting me):

"Even molecular evolutionists know full well that partially new genes en route to evolving fully functional new genes (called incipient genes) have no selection value in evolution and are not preserved, so only fully formed genes could be selected. This, as even Bernd-Olaf Kuppers puts it, is an unsolved and unsolvable problem for molecular evolutionists."

>You should look up the Drosophila gene jingwei in Flybase. Jingwei is a new gene, formed by a retrotransposition event. Jingwei is a chimaera between alcohol dehydrogenase and another gene. The molecular function which jingwei has assumed is not known...

>: Under such circumstances, it is simply improbable to evolve a new gene by tinkering with a duplicated gene within the short time-frame in which the distinct organisms are said to have evolved.

>See jingwei. Also, the most likely scenario for a duplicated gene remaining in the genome is if it assumes a different role. There are several plausible mechanisms for this, and I will detail 2.

>1) Suppose the parent gene is expressed in two different tissues, and this expression is guided by specific controlling elements for each tissue. In other words, enhancer A drives expression in tissue A and enhancer B drives expression in tissue B. Duplication of the gene results in two copies. If one loses function of one enhancer, then the other copy loses selective pressure on the opposite enhancer. In other words, a duplication event can lead to a splitting of responsibilities between the two duplicated pieces.

Please note that Keith simply proposes a scenario, and then simply assumes it to be correct. From where does Keith derive the enhancers in the first place? His many "if" statements are simple propositions, but the last sentence is a conclusion based on these propositions and assumptions, without any corroborating validation. Unfortunately in evolutionary discussions we tend to do that a lot.

>2) Transposons. Senapathy is quite clear in his feelings towards the potential role of transposons in evolution. He titles one section Analysis of an example organism: Mutations of the fruit fly indicate that transposons can have no evolutionary contribution I contrast this bold statement, and the rhetoric which tries to back it up, with the recent publication Transposon-induced promoter scrambling: A mechanism for the evolution of new alleles Kloeckener-Gruissem and Freeling. Proc Natl Acad Sci U S A 92: 1836-1840 (1995). The authors describe a complex transposon-induced rearrangement in Maize which leads to alteration of the expression pattern of the alcohol dehydrogenase gene. The gene's expression is increased in some tissues, decreased in others, and remains the same in still others.

>In this and jingwei we see two different experimentally- demonstrated routes to genes moving into new developmental pathways, something Senapathy is certain is impossible. In one (jingwei), retrotransposition of a gene has resulted in a hybrid gene with the expression pattern of one parent. In the other (Maize adh), the developmental expression pattern of a gene has been altered by a transposon-induced DNA rearrangement.

>: The reality is that the set of genes of any organism is : essentially constant.

>Ms Jingwei would respectfully disagree with you on this.

Here Keith is talking about an outcome whose cause is well known, but which outcome has nothing to do with evolution -- except that he believes it to be so. As I have discussed in my previous posts, many normal DNA mechanisms such as the DNA recombination can sometimes lead to erroneous combinations. Sometimes intragenic recombination can occur due to unequal crossing over, resulting in chimeric genes. Such genes are either deleterious to the system, or are neutral and will be randomized. They are neither caused by any evolutionary mechanism, nor have any evolutionary consequences. I have discussed that such genes could even cause cancer (page 170 of my book). A clear example of such a gene is v-fgr onc, which is a recombinant between a portion of actin gene and a tyrosine-specific protein kinase gene (Naharo, G., et al, Gene Product of v-fgr:onc Hybrid Protein Containing a Portion of Actin and a Tyrosine-Specific Protein Kinase, Science, 223:63-66, 1984). This gene that is present in a retrovirus (Gardner-Rasheed feline sarcoma virus) can cause cancer. Clearly this does not mean that this gene has some evolutionary value.

The two alleles Kloeckener-Gruissem and Freeling have led to only slight variations in essentially the same Maize organism. I have explained many such incidental variations in my book. In the case of jingwei, as Keith has rightly pointed out, we do not know the function of the chimeric gene. It is possible that it is simply the result of a random recombination event, and such random recombinants have no function. It is important for us to realize that such random recombinants of genes in a genome are the unavoidable erroneous consequences of the normal mechanisms of DNA recombination, but by no means do they carry any evolutionary consequences.

Keith has made some interesting points, but they only reiterate the fact that mutations cannot cause evolutionary change. It is important not to confuse the issues here. There is no doubt that mutations do occur within the genomes, and that point mutations and recombinations change DNA and sometimes produce chimeric genes. But we must realize that DNA mutations occur only because it is an inherent biochemical property of DNA to mutate and change. And it is even more important to realize that, because of the extraordinary tolerance of proteins to accept amino acid variations, and because of the degeneracy of codons, most of these mutations are simply neutral. They only change the constant set of genes in a genome into its normal variants. The rest of the mutations only cause genetic abnormalities. No more! The constancy of the set of genes and the genetic network of a genome of an organism is never affected. I certainly do agree that a mind trained in evolution always tends to view any DNA changes as "causing some evolution," or "contributing to evolution," or "having some evolutionary value or advantage." I am fully aware of that orientation, for I was myself an evolutionist for a number of years, and indeed used to marvel at the beauty of evolution through these thoughts. I now know that I was only caught up in the belief system, without really knowing the underlying truth.

A very important thing to note here is the fact that is indeed largely unknown to even molecular biologists. When I say that there are numerous distinct unrelated genes in distinct organisms, I mean totally unrelated genes. For example, there are nearly one thousand proteins in the vertebrate plasma. Not even one of these proteins is found to be present in any of the invertebrates, although numerous explorations have been carried out. Only a handful of molecular biologists are doing this kind of exploratory research (such as Russell Doolittle of the University of Southern California), and they are simply puzzled that a whole set of proteins (genes) present in vertebrates are completely absent in invertebrates, the very organisms from which the vertebrates are assumed to have evolved. It is absolutely improbable for this large set of totally new genes to have simply evolved in one single step from an invertebrate to a vertebrate.

Invertebrates have their own set of plasma proteins and cells. In fact there is no relationship between the "blood" of an invertebrate and that of a vertebrate. And, in fact, the term "blood" is used only generically here, and there is absolutely no relationship between the blood of invertebrates and that of vertebrates. In addition, the vertebrate blood coagulation system of cells and proteins is completely absent in all of the invertebrates. Invertebrates, on the other hand, have their own system of coagulation cells and proteins (called coagulons) that help seal cuts on their body surface. (Note also that different sets of invertebrates seem to have different protein and cell systems for such functions.) Vertebrates have immune systems that are totally distinct from those in invertebrates. Vertebrate immune systems are based on immunoglobulins, T cells and B cells, whereas invertebrate immunity is based on a totally different kind of molecule called lectins and kinds of cells that are unrelated to the T and B cells. (I have described these details and more in my book in Chapter 9.)

A careful analysis of this scenario reveals that vertebrates could not have evolved from invertebrates. The vertebrate/invertebrate distinction is only one example that I cite to illustrate the point. Such totally unrelated genes are present in numerous distinct creatures, showing their independent origins, albeit from a common pool of genes in one single primordial pond. This, I believe, is one of the major corroborations from molecular biology for my theory: that the genomes of numerous distinct organisms must have been assembled independently from a common pool of genes in a single primordial pond, leading to the presence of not only distinct unrelated genes in different genomes, but also many essentially same genes. This scenario predicted by the new theory is what we really observe in living organisms, and not the one predicted by evolution theory. It is time for us to take a fresh look at all the details of the molecular scenario and honestly ask ourselves which theory is really valid.

From Arlin Stoltzfus in bionet.molbio.evolution:

>The Independent Birth of Organisms theory proposes that the genomes of all organisms are "immutable" and arose "independently." On page 311 of Senapathy's book ... there is a diagram that nicely illustrates the meaning of "independent" origins. I have attempted to replicate the diagram below. The original has a circle around the central text, with 8 separate arrows pointing outwards to the 8 separate organisms:

                 rat               |             millipede
                     \             |           /
                      \            |          /
                            common pool of   
     jellyfish ------- the genetic code and the ------- frog
                      genetic machineries in the
                            primordial pond
                      /            |         \
                     /             |          \
             dolphin               |            crab
                              sea anemone
>This idea can be distinguished experimentally from the hypothesis of common ancestry + descent with modification (i.e., rats+dolphins arose from a common mammal stock; jellyfish+anemone arose from a common coelenterate stock), as follows. One may scan the sequence databases for a gene of interest that has been characterized in all or most of the above species, e.g., suppose it is a gene for 16S rRNA. One may make a bifurcating dendrogram from this sequence information using a phylogenetic inference package (e.g., PAUP, Phylip). Under the common ancestry theory, the dendrogram for 16S rRNA is interpreted as an estimate of the organismal phylogeny, representing the course of evolution from a common animal ancestor, through descent with modification.

>A single dendrogram will not allow us to distinguish common ancestry vs. independent birth. Under the independent birth theory, the 16S rRNA sequences for crab, anemone, rat, dolphin, frog, etc. are proposed to have been drawn from random sequences in the primordial pond. A dendrogram can be constructed from these randomly generated sequences -- but the pattern of branching that results represents nothing in particular, only the stochastic process of drawing from a pool of random sequences.

>However, the two theories have different predictions about what will happen if we construct dendrograms from additional genes and compare them with each other. The common ancestry theory predicts a relationship of congruence -- the trees inferred from 16S rRNA from rat, frog, anemone, etc. should tend to match the trees inferred from tubulin (or whatever) genes from rat, frog, anemone, etc.. In this view, the trees are not independent, but arise from a common set of processes of descent with modification. By contrast, in the independent birth theory, the trees are independent in the exact sense of "independent": they are derived from drawing random sequences from the primordial pond, and no particular relationship is expected.

>This creates the conditions for an objective and falsifiable test of the independent birth theory. One may quantify the expectations for random congruence of tree topologies, as predicted by the independent birth theory, and compare this to observations. A significant tendency for the trees inferred from different genes to match would exclude a major tenet of the independent birth theory, which would then have to be either abandoned or revised extensively. At the very least, the name would have to be changed from "Independent Birth of Organisms" to "Non-independent Birth of Organisms."

>By the way, gene sequences are readily available from rat and frog, but not (yet) from millipedes, dragonflies, crabs, anemones and dolphins, so I would suggest that we substitute fruitfly, mouse, human, C.elegans and chicken. Before actually making the trees, though, perhaps Dr. Senapathy will comment on whether the test is fair.

In my theory, the genes for the components of cells and cellular structures such as the ribosomes had been already established (available) in the primordial pond before the formation of any living cells. These sets of genes for the cellular components were like reagents (available in multiple copies) that could be used in many different genomes (i.e., by any and all life arising from the common gene-pool). Under these circumstances, the fundamental cellular structures were the same, and the fundamental genetic mechanisms ought to be the same when many genomes were assembled from a common pool of genes in a single primordial pond. But the genomes -- the set of genes and the developmental genetic network (pathway) of the different genomes -- were different.

Even if this is what had exactly happened, still we can "construct" a "phylogenetic tree" for the molecules such as the 16S rRNA. Such trees are only false trees, and do not represent the reality. Please note that each gene included in the different genomes could change into its many normal variants with sequence changes. If we analyze these RNA sequences with the assumption of independent genome assembly, I am sure we shall see that the results will fit the new theory. Please note that I have not said that entirely different rRNA genes (each arising from a distinct random sequence) were included in different genomes (i.e. distinct organisms). What I say is that it is essentially the copies of the same rRNA genes (and genes for other cellular and biochemical components) that were included in the different genomes. They changed randomly in the different genomes without losing the essential structure or function, only changing to their normal variants. These normal sequence variations are those that evolutionary molecular biologists now use to "construct" a misleading phylogenetic tree.

From in

>Senapathy's theory may have some validity, I believe, but I believe he's trying to extend it too far. Some thoughts: -- It certainly makes some sense that there may have been multiple origins of life, given that it happened at all. It's certainly possible, then, that these different forms of life then somehow combined genetic components.

>Senapathy says that the components were all just floating around in the primordial pool. The primordial pool, in a literal aquatic sense, would have been huge, while the amount of genetic material would have been extremely scattered. A simple life form would have had to take an incredibly long period of time to accumulate a lot of diverse DNA floating around, as dispersed as it must have been. An important alternative, of course, is that there were small pools (aquatic, that is) in which conditions were right for concentrated creation of DNA, in which case it would have been easier to accumulate the genetic material, and such pools could have occurred at diverse points around the world, thus leading to potentially very diverse and separate forms of life.

I agree. In fact, I have been saying that a small primordial pond with a finite amount of DNA is sufficient for the occurrence of multitudes of genes (Chapter 7 of my book). I have computed the amount of random DNA needed for the occurrence of billions of fully formed genes: random DNA sequences totaling approximately 10^26 nucleotides is sufficient for the presence of almost any gene coding for a protein with almost any biochemical function. This quantity of DNA by weight is really not too much either: it is approximately 100 pounds. Please contrast this with the premise of evolutionary biologists who say that even a short gene is improbable in a DNA with the mass of the whole universe -- based on which they say that even the simplest life is really improbable on earth but that it should have somehow occurred by an improbable freak accident simply because it is a reality that we are all here. Compare the amount of DNA that we have computed here with the amount of DNA available in one human individual, which is about 60 grams and 10^23 nucleotides. It means that the amount of DNA available from just about 1000 human individuals -- if this amount is present as purely random sequences -- is far more than sufficient to contain billions of distinct genes. In fact, there is no reason why genome assembly could not have occurred in a concentrated solution. Under this circumstance, many genomes could be assembled independently, and these genomes could mix and recombine among themselves.

>I think it unlikely that shared genetic sequencing (as opposed to shared genes, which could have been fairly common) would have occurred as spontaneously in parallel as Senapathy suggests -- the laws of probability make it very unlikely. There must have been other ways. There are various modes of sexual reproduction, of course, which would have been most unlikely in their modern forms between diversely originated unicellular or even simple multicellular creatures. I believe that the role of failed cytophagy has been probably under emphasized in the evolution of cells, and was probably the origin of sexual reproduction, undoubtedly of mitochondria, and possibly indirectly of the nuclear membrane. But there are other ways, too, for information to be shared -- for instance, a cell may have carried a particular DNA sequence, and for some reason ejected it as not wanted, whereupon another cell may have absorbed it. In any case, there's too much complexity in most multicellular life-forms for them to have sprung full-blown from the brow of the genetic Zeus, as it were. There HAD to have been intermediate steps; I don't accept that part of his theorizing. It's possible that certain groups -- phyla or related phyla, however, arose entirely independently, but certainly not all phyla.

I have performed detailed computations of the probability of genes' part similarities (such as those that occur in some protein domains among different proteins) in genes that can occur independently in random sequences. These computations show that the probability of similar genes occurring in independent random sequences is quite high. This notwithstanding, it is highly probable for the different genes and genomes to become available in multiple copies in the primordial pond, and for them to recombine among themselves. I have called this "genome-mixing" in the open primordial soup, and the production of newer genomes with similarity to other genomes. In fact, these predictions are well borne out in the actual organisms living today and those that have become extinct, in exhibiting mixed anatomical characteristics which cannot be accounted for by any evolutionary mechanisms.

>I think he's overlooked two important mechanisms in speciation/evolution:
>1. Polyploidy:....
>2. Population explosion into new habitat:

I have not overlooked these phenomena. I have discussed in detail how all the known mechanisms of genetic change and rearrangement cannot be and are not the cause of the assumed evolutionary changes (Chapter 4). Here I have discussed how polypolidy can explain the origin of some related plants, but that it cannot explain the origins of any of the distinct animals, which is even accepted by many prominent evolutionists (page 176-179 of my book).

>Senapathy and many other geologists and biologists are guilty of a kind of intellectual arrogance when they claim that certain groups of fossil life originated in an explosion at a certain time. It may have happened; WE DON'T HAVE PROOF. What we do know is that the fossil record from those times is sparse, sporadic, and exceptional. We only have small windows in which to glimpse the past.

In fact it will be good if we can agree that we should take the fossil scenario with a grain of salt. That should apply to the evolutionary arguments also, not only for the Cambrian explosion but also for the later fossil record. We may not know exactly how things got fossilized. The most important thing I want to emphasize is the following: Even if we completely ignore the fossil scenario, and analyze the probability of the origins of life based on genes and genomes and compare these with the actual genes and genomes, we should be able to come up with reasonable answers concerning the origins of life and organisms. This is precisely what I have done in my book, and I am finding repeatedly that numerous distinct organisms did indeed originate independently by independent genome assembly from a large common pool of genes. In fact there is ample molecular evidence for it from the living world (Chapter 9). Each organism remained essentially fixed in terms of its anatomy and organismal functionality, changing only to slightly changed varieties and similar species over the millennia between their origins and the present time.

>I think the one original part of Senapathy's theory that most merits credit is the idea that most simple DNA sequences (genes) have been around since the origins of life, and that many (unicellular) life forms originated independently, albeit sharing genetic material.

I thank (s/he has not given a name) for understanding the theory in essentially the form that I have proposed it. It is only that if probabilistically sufficient numbers of genes could exist that were capable of producing many unicellular life forms (even a single one for that matter), then the same probability will inevitably yield the genomes for many multicellular organisms as well. This is mainly because we are talking about the extremely high probability of only the split- genes occurring directly in the primordial random genetic sequences, whose combinations will yield the genomes of multicellular organisms directly from the genes that randomly occurred in the random primordial DNA sequences. Furthermore, I have shown that these genomes directly enabled the morphologically complex eukaryotic cells to come alive with all the complexities such as the nucleus and so on, contrary to earlier belief that the morphologically simpler prokaryotes should have been the mother of all life, including unicellular eukaryotes. (See my forthcoming article in the journal Science on this subject.) Thus, what we are discussing is an entirely new world view, but scientifically fully supported and corroborated not only by the probabilities of genes and genomes, but also by the structural and sequence features of genes and genomes of actual organisms that are living today, which could be explained only by my theory and by no other theory.

Jeff E ( wrote:

>Whew! You have a much better grasp of this than I do. I'm not sure how your theory differs from evolution as I understand it. As a student of molecular biology myself I have found not the theory of evolution hard to grasp, but the insistence of evolutionists to use molecular evidence in supporting the theory.

My theory is quite different from conventional evolutionary theory in that it says that numerous distinct organisms had originated from a primordial pond (essentially inanimate matter) in contrast to the evolutionary argument that one single cell arose first from inanimate matter on earth from which all life on earth sprang by means of descent with modification. Please note that evolutionists do not have a mechanism for the origin of the genes of the first single cell, considered to be the mother of all organisms that arose on earth. While the origin of the first single cell on earth is an improbability for them, surprisingly, they go on to theorize that all other complex organisms evolved by means of mutating the genes in the "simple" genome of the original single cell. Please also note that they start their argument from assuming that the original single cell was a prokaryote, and that is the reason why they get into the problem of being unable to explain the origin of the genome of the first cell, even in theorizing about it. It has been time and again said by noted evolutionists such as Jacques Monod and Bernd-Olaf Kuppers that even the simplest life is improbable on earth, which they conclude by means of a simple probabilistic argument concerning the origin of the genes of the prokaryotes. In contrast, I start my arguments by demonstrating that it is only the split-genes, that are typical of all known eukaryotes, that were the genes that simply occurred in random DNA sequences in the primordial pond, in fact in a quantity of random DNA that is reasonably very small. When we start the argument with this basis, one can see very clearly that multitudes of different genes, in fact almost any gene for almost any biochemical function that one can think of, can occur in the small finite quantity of random DNA in a biochemically rich primordial pond.

In essence, my theory is distinct from the evolutionary theory, but it is not any creation theory either. It uses the chemical evolution studies and arguments, and says that there was a great deal of molecular selection mechanisms that took place in the primordial pond, even before the first living cell ever came into being. I show that essentially the genomes of numerous distinct organisms originated from a large common pool of genes, that originated in random DNA sequences that were first chemically and then enzymatically synthesized in a biochemically rich primordial pond (that is, essentially from inanimate matter.) I also show that once the genes of an organism assembled as a genome in the primordial pond and the living organism was established, then its genome was fixed, and its genes could not be changed by means of any genetic mutation and rearrangement, although many kinds of genetic mutation and rearrangement do take place as an unavoidable property of DNA and genes. These mutations simply do occur in a genome causing a certain amount of genetic flux only in the physical sense but not in the functional sense. That is, a lot of genetic flux is ongoing in every distinct organism that originated independently by independent genome assembly in the primordial pond, but the set of genes in each genome is constant, and the Developmental Genetic Pathway of every organism is also fixed. It is in fact a myth of molecular evolutionary argument that all existing genes of all complex living organisms originated from the set of genes of the simple genome of the simple one- celled organism that is considered to be the mother of all living organisms -- the first origin of whose genes and genome is a mystery to evolutionary theory.

>When you bring this before an evolutionist however, you will hear about genes being unreliable because of backmutations.

True. This is what I face whenever I discuss the theory with ardent molecular evolutionists. However, I find that many molecular biologists at NIH and at universities are open to my arguments, although they are not the ones who post on these forums. It is mostly those who are still bent on not seeing the truth who seem to be posting here.

From Andrew Roger in bionet.molbio.evolution (who begins by quoting me):

"It should also be noted that my theory is able to explain the presence of utterly unrelated genes in distinct organisms -- a phenomenon that evolution theory cannot explain at all."

>This statement is not correct. First of all, any reasonable theory of molecular evolution suggests that with time the sequences of genes will change by mutation. If genes are separated by a speciation event then each resulting group of organisms will contain genes which will be changing independently as time goes on. It does not take much of an intuitive leap to realize that given enough time homologous sequences will drift to the point where it is no longer possible to detect their relationship. This is what is presumed to happen, for instance, for portions of non-coding DNA such as introns. For coding regions, this also occurs (albeit at a slower pace). For a description of molecular evolutionary models of these processes please check Li and Graur's text, The Fundamentals of Molecular Evolution, 1991, Sinauer Associates. Look specifically at chapters 3 and 4. In addition there is no reason why new genes could not evolve from what was originally non-coding DNA in an ancestor of a modern organism. Perhaps the ORFs would start out small, but they could grow by selection operating on variants which were a little longer (for instance where a mutation changed a stop codon into something else like a glutamine codon. NOTE: this requires only a SINGLE POINT MUTATION). And given enough time they could become a decent sized gene. What the hell is the matter with this kind of explanation of the evolution of novel genes? I just don't get it.

This whole paragraph is composed of belief statements. This is how I used to think regarding new genes when I was myself an ardent evolutionist, but it took me a long time and extensive analysis to see otherwise. I must point out that I have carried out many different kinds of analysis based on the arguments given by Andrew Roger while I was at the NIH Division of Computer Research and Technology and at the University of Wisconsin Biotechnology Center and Department of Genetics and more recently at my own genetics R&D firm Genome International. And they show that new genes cannot evolve by these means. Because DNA is prone to mutations, and because mutations do take place in the genes, we tend to think, having been taught the attractive and appealing evolutionary theory, that these mutations can lead to new genes. Also, surprisingly, when we make such belief statements that DNA mutates and genes mutate and they form new genes, because changing even one gene into an entirely distinct gene only takes changing the four characters of the genes and introducing some more characters or deleting some characters. But, in reality it does not work. If we analyze the details of genes and the purported mechanisms very carefully, we can see clearly that new genes cannot evolve by these mechanisms. Why should we be hung up with the evolutionary argument that does not work? When I can clearly show that many many distinct split-genes can indeed simply occur within a finite amount of random DNA material that could be reasonably present in a primordial pond, and which can conglomerate into numerous genomes of many distinct organisms, as complex as we find today on earth, and which arguments explain all the scenario of life on earth -- molecules, organisms and fossils -- why should we not take a look at this theory with an open mind?

>A and B are different organisms belonging to different phyla. We cannot fully explain how to get (using evolutionary steps) from group A's form (assume A is ancestral to B) to B's form. Therefore an evolutionary explanation is wrong. The problem with this sort of argument is that the lack of a currently exhaustive explanation for an evolutionary transition is not necessarily evidence that none exists, it is evidence that either we need more data or we need to think harder about how to get from A to B.

Precisely! I am happy that Andrew Roger accepts fully that there is a lack of exhaustive explanation for an evolutionary transition from one distinct organism to another. As Andrew says, I agree that the current lack of an argument for an evolutionary transition is not necessarily evidence that none exists, but when we think harder and carefully analyze the molecular and all other evidence, we find that there may never be an explanation for such evolutionary transition. In fact, as evolutionists such as Guy L Bush say (quoted in my book, Chapter 4) any real data regarding the genetics of speciation is woefully lacking, and speciation has only been theorized and spoken about extensively. Again, when there is no evolutionary explanation for the transition from one distinct organism into another, and when I can offer a fully valid explanation for the origin of many distinct organisms from a common pool of genes in a common primordial pond which is fully corroborated by almost all the available details of life on earth, why should we not take a genuine look at it with an open mind?

From Weisman ( in

>I'm not a professional biologist, but I can't help feeling one important question had been ignored by both Dr. Senapathy and his critics. Assuming all his calculations about the probability of a new genome self assembling are correct, how does this lead to a phenotype?

This is a good question. I have discussed this extensively in my book (Chapter 8). The ability to express a genome is built into the genome that originated in the primordial pond. This is what I call the Developmental Genetic Pathway (the DG pathway) that takes the expression of the genes in a genome through a genetic network (network of events of switching on and off of various genes). Please note that the origin of these networks from a pool of genes boil down to the probabilities of genes and sequences, and the networks of genes. When we carefully analyze the existing data regarding these aspects, we can see that the probabilities for assembling the split-genes into a genome with a specific developmental genetic network is very high. Once such a genome is assembled into a typical eukaryotic cell (which is analogous to an egg cell of any of today's living multicellular organisms), it can pretty much "express" the genome into the embryo and the fully formed creature.

Please note that I do not say that the genomes of only the viable organisms were formed in the primordial pond. In fact, I say that a multitude of genomes that were meaningless were also formed. Also, numerous genomes of multicellular masses that were meaningless as viable living things were also formed. In fact, it is only a small fraction of all the combinations of genes as genomes in the primordial pond that led to viable organisms. However, the number of genomes that could be formed from the set of genes that could be available in the small finite amount of random primordial DNA (~100 pounds) was so enormous to result in millions of distinct organisms.

From Arlin Stoltzfus in

>Senapathy argues that the necessary machinery for replication, transcription and translation were already present in the "primordial pond," and that this allowed spontaneously assembled genomes to be "expressed" as cells. The cells, in turn, develop into organisms. The exact nature of this process of "expression" is consigned to a black box, then it is argued (in the following passage) that this black box is necessary:

"Logically, almost everyone would accept that conducive conditions must have existed in the primordial pond at least for single-celled organisms to have originated, because, without them, absolutely no multicellular organisms would ever have been possible. In fact, chemical evolutionists and other evolutionary biologists unanimously agree that the conditions in the primordial pond must have been conducive for the evolution of single cells, at least bacterial cells. We have shown that it must have been the unicellular eukaryotes that directly assembled their genomes in the primordial pond, and not the prokaryotes. Therefore, we can logically postulate that there was present such a condition on earth at some time for the formation of the single-celled eukaryotes directly from biochemicals in the primordial pond." [from Independent Birth of Organisms, P. Senapathy, Genome Press, 1994, p. 297]

>In its barest form, the argument is i) genomes and organisms must have arisen spontaneously (i.e., without an incremental evolutionary process) and independently from random sequences; ii) it is a logical necessity that cells first arose from non-cells, and ultimately from chemicals; therefore iii) it is necessary that cells were expressed spontaneously from random sequences (chemicals) in a primordial pond (though we may find this process difficult to fathom).

>The quoted paragraph explains premise (ii), and the conclusion more or less follows from the premises (i) and (ii). The crux of the matter is premise (i).

I thank Arlin very much for explaining my theory in a nutshell. One thing I would like to point out is that the "black box" boils down to probability of genetic networks, which I show is really high, as explained above.

From Tim Ikeda in bionet.molbio.evolution (who begins by quoting me):

"It should also be noted that my theory is able to explain the presence of utterly unrelated genes in distinct organisms -- a phenomenon that evolution theory cannot explain at all...."

>Horizontal transfer isn't a known phenomenon?

There is some evidence that horizontal transfer of genes may occur more often between prokaryotes, and rarely between eukaryotes. Even the noted evolutionary biologist Douglas Futuyma has stated that there is little evidence so far that transfers of this kind have occurred frequently in evolution.

That aside, we have to first realize that molecular evolutionists have no way of explaining the origin of the genes of the ancestral first cell's genome. Also, as I have demonstrated in my book, starting from the genome of this first cell, there is really no way that new genes of all the other organisms that are supposed to have evolved from the first mother cell can be evolved. When this is the case, how can the viral vectors transfer genes between organisms that are supposed to be evolving? What the vectors have is only a set of fixed genes, which means that they can only transfer the same genes back and forth. I have discussed this in my book under the subtitle "Addition of new genes into a genome by viral vectors: Putting the cart before the horse."

From Keith Robison:

>Weisman ( wrote: "I'm not a professional biologist, but I can't help feeling one important question had been ignored by both Dr. Senapathy and his critics. Assuming all his calculations about the probability of a new genome self assembling are correct, how does this lead to a phenotype?"

>Oh, don't worry -- Senapathy has an explanation for this. He postulates the formation of "seed cells" which develop into whole organisms, and the existence of lots of proteins in the primordial pond.

Yes, I do say that the genes for lots of proteins did exist in the random DNA sequences in the primordial pond. And I do postulate the formation of "seed cells" which develop into whole organisms. I challenge any one to read my theory completely and then to show how it is mistaken.

From David Coutts in

>I have not read Senapathy's book, only his web page, and the newsgroup discussions, but I understand that he is suggesting that organs such as eyes are supposed to have evolved direct from his "pond" with out a sequential process of adaptive evolution, just selection. If this interpretation is wrong, would someone please spell out for me exactly what he is supposed to be saying.

Your interpretation is essentially correct, except that the set of genes for an eye in toto could originate from the primordial pond, and not the tissues of the eye per se. Note that there are numerous types of eyes in the animal world that are structurally unconnected. Based on the unconnectability of the distinct kinds of eyes, Ernst Mayr and Salvini-Plawen (On the Evolution of Photoreceptors and Eyes, Evolutionary Biology, 10: 207-263, 1977) have proposed that more than 100 types of eyes had evolved in separate lines each from a creature that lacked even a photoreceptor. Despite this fact, modern evolutionary biologists are trying to propose that all eyes still should have evolved from a single ancestor, based on the fact that there are some similar genes that participate in the development of eyes in many distinct kinds of creatures bringing forth the distinct unrelated eyes. The presence of similar genes that go to develop the distinct kinds of eyes in distinct unrelated organisms is explained in my theory by the inclusion of similar genes in distinct genomes from the common pool of genes. That is, these distinct creatures that originated in the primordial pond only share their genes in the primordial pond's common gene-pool, and have not evolved organismally from one another. It is very important for us to understand that this is the only way by which we can explain the presence of similar genes as well as completely unrelated genes in organisms that are totally unrelateable based on organismal structures.

Again from David Coutts:

>Does he really suggest that complete and well adapted organisms (and lots of "hope_less_ monsters") are supposed to have crawled out of his pond, in sufficient numbers that after natural selection there were enough left to make up a fully complete ecosystem? And if so, over what time-scale, and what range of organisms were supposed to be present? This scenario is so absurd that I assume that I have misinterpreted what I have read here, pleas someone clarify this for me!

Again, you have essentially summed it up correctly, although I hardly agree with your sense that the theory is "absurd." In my theory, the genomes assembled randomly, without any concern for the types of organisms they would produce. In fact, as I stated above in response to another post, multitudes of multicellular masses (the "hope_less_ monsters" you mention) should have resulted from many genomes, and only rarely a viable one. But, the number of genomes probable from a primordial gene pool containing billions of genes (from only a finite amount of random DNA of approx. 100 pounds, which will total approx 10^26 DNA nucleotide characters) is indeed enormous. And so, the number of viable organisms out of this crop will still be in the millions.

What range of organisms could be produced in this scenario? A good question. The answer: Almost all kinds of organisms that we know on earth. The explanatory ability of my theory is that the mechanism and the probability of the formation of the genome of one creature are the same as that for any creature, simple or complex. It should be noted that the genome of the simplest unicellular eukaryote is no less complex than that of the most complex multicellular organism. The complexity of the genome of an earthworm is essentially the same as that of a frog or a mouse or, for that matter, of a human. It is important to realize that if one genome can be formed from a large pool of genes -- which is absolutely essential for any living thing to have come on earth -- then numerous genomes with similar complexity could arise from the same pool of genes, but only producing different organisms that may have a world of differences among their structural and functional capabilities. The time scale however is hard to predict. However, we should realize that the DNA molecule is very tough and stable. It is becoming increasingly apparent that DNA can be extracted intact from thousands-of-years-old mummies, and from thousands-of-years-old paintings that used animal tissues (ref: last week Science). The whole process of independent genome assembly could have taken many thousands of years, which is reflected in the Cambrian explosion. I should say, however, that more research is needed to understand the time-scale for this.

Finally, I want to emphasize an important point here. It is very understandable that all of us who were trained as evolutionary biologists and molecular biologists tend to feel that evolution is an established fact. Years ago I would have been extremely angry at anyone who said that evolution by descent with modification was not true and that evolution theory, considered central to modern biology, is essentially incorrect. In fact, evolution has been the most fascinating thing in my life, and I long admired it and embraced it with all my heart. It enchanted my mind like poetry, flowers and music. And it was only as an ardent evolutionist, fourteen years ago while I was researching at the NIH, that I realized that organismal evolution was not needed to explain the origin of organisms. I had to wait for more than a decade doing a great deal of research solely to prove it and to demonstrate how organisms could have originated. Contrary to the speculations of some of my critics, I was not interested in independent births for some ulterior motive. I conclude that independent births occurred only because my research points to it. Please understand that I am not a religious person at all, and that I have not arrived at my conclusions without excruciatingly thorough analyses, research and syntheses, all of which are documented in my book.

I say again that my theory is fully corroborated by almost all the molecular and biological details of living organisms. I have not proposed anything antiscience at all. In fact, I fully accept that chemical evolution did happen. The only thing I say that is that the chemical evolution itself is able to explain the origin of almost all organisms directly from the primordial pond. Consider that evolutionists have no explanation for the origin of the one single cell that is assumed to be the mother cell of all organisms. But I can explain not only one single cell but numerous cells that were the egg cells of numerous distinct organisms originating essentially independently from a single primordial pond. When I say that the genomes for fully-formed complex organisms originated directly from the primordial pond (i.e., essentially from inanimate matter), it may seem to be unbelievable. But this is extremely probable and, based on all the available evidence, is most likely the fact. If this theory is fully corroborated by available evidence, why should we not take a fresh look at it with an open mind, without getting unduly angry? That is all I ask for. I am not asking you to accept the theory at face value. But it is patently unfair to summarily dismiss an idea simply because it opposes evolution.

I can't help noticing that many of my critics have raised questions that are fully answered in my book, and I therefore feel obliged to note that one can reasonably comment about a theory only when s/he completely understands it. I am confident that most reasonable, educated people -- including trained, qualified scientists across all disciplines -- will agree that my conclusions are at least plausible if they will only take the time to read the complete theory as I have presented it in my book.

It has been a pleasure taking part in the lively discussions so far. I invite more questions, and I hope to continue to enjoy our discussions.

Periannan Senapathy

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