Replies to Senapathy Q & A Number 1


From Keith Robison: I am happy to see that Senapathy has chosen not to ignore the comments of myself and others. There are two objections he did not approach, perhaps because they got lost in the shuffle. (I will answer some of his counter-critiques in another post).

These two comments are tied together by a common thread. Senapathy denies the commonality of many taxa; he claims that mammals (let alone vertebrates) are artificial groupings of organisms which sprung independently from the primordial soup. We can ask if there are conclusions we can draw from Senapathy's premises which are contrary to the facts, and whether there are facts which are inconsistent with Senapathy's premises.

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.

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.


From Keith Robison: I would like to point out one of the most serious impossibilities of Senapathy's theory.

To restate, Senapathy claims that most living taxa sprung independently from primordial soup at various times, and that the sudden appearances in the fossil record correspond to these emergences.

Senapathy's conception of the primordial pond contains not only organic molecules, but gene-sized DNA molecules. Biologists have a term for this sort of mixture: rich culture medium. If any bacteria or fungi existed, they would digest the DNA (without even trying; most organisms generate lots of external nucleases) and eat everything. As soon as bacteria show up, the soup disappears and the generation of new living forms stops.

So, in order to believe the Senapathian scenario, you must also believe that bacteria and fungi did not emerge until after the emergence of the last new forms in the fossil record. Imagine -- for hundreds of millions of years Earth got along without decomposers, while full-flung critters emerged from the primordial pond.

Completely implausible.


From Keith Robison: (quoting Dr. Senapathy) "Yes! I certainly say that it is far more likely to assemble the genes for constructing an eye directly from the primordial pond's vast gene pool than to evolve an eye starting from a primitive organism that lacks even a photoreceptor."

No! You explicitly state that it is IMPOSSIBLE to evolve an eye. The simulation shows that it is quite straightforward, given a photosensitive spot. You are now stuck arguing that photoreceptors can't evolve. Since a photoreceptor is just a light-sensitive protein keyed into a signal transduction pathway, both common elements, you are in a serious bind.

"This fundamental theme of organizing the genes for even morphologically complex organs directly from the primordial pond is precisely what the new theory is all about. The book provides many valid scientific principles and corroborations to demonstrate this thesis."

"Certainly no computer simulation is acceptable unless it characterizes mutational process at the level of DNA, genes and proteins. To my knowledge no one has ever demonstrated the evolution of a complex eye by any kind of : simulation involving the fundamental blueprint of DNA and genes, and in my view no one ever will."

I don't remember your simulations doing this. You certainly didn't evolve a working genome from random sequence. This is an impossibly high standard which no scientific simulation claims to reach.


From Keith Robison: 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. His vision of a primordial pond full of chromosome-sized DNA is greatly at odds with the properties of DNA (not only does it require a lot of energy to generate that DNA, but as any scientist working on the genome project can tell you, DNA that big is simply mechanically-unstable unless packaged by complex mechanisms such as those in the cell). 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 (PNAS). Publication in this journal is used by Senapathy as endorsement of his theory and proof of its validity.

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...)

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).

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.

In short, Senapathy's theory is fatally flawed at every level, from his proofs of the impossibility of macroevolution of organisms, through his scenario for a primordial sequence pool, and ending with his underlying theory of gene assembly.

In closing, I would just like to point out the irony of Senapathy's title on his original postings: "Genome Research Refutes Evolution"

Senapathy's book ignores just about everything that has happened in genome research. Why? Because it would be extremely inconvenient for him -- the mapping and sequencing of many genomes is revealing in great detail the common heritage of organisms which Senapathy declares are lines sprung independently from the primordial pond. His posting title is completely at odds with reality.


From Periannan Senapathy:

I read Keith Robison's questions and comments, and I thank him again for his continuing interest in my theory. All of the points he raises are easily explained by the theory, and in fact most are discussed in depth in the book. I will be responding to his and others' comments collectively and in detail...


From David Weisman: 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?

Do I seem to recall the first mammals were insectivores? I don't know for sure if this applies to both placental or non placental mammals. Let us suppose all the chromosomes for a rat sized insectivore self assemble into a usable genome. There are no proteins to build a cell from this genome! Even if we assume the proteins are part of the primal pool, could a single cell grow into an entire animal in any conceivable primal pond?

I realize all origin of life scenarios have major challenges inherent to anyone who wants more than speculation, but unless I've missed something, this one has an even harder road to travel than the others have been shown to have. Could a mammalian reproductive cell really grow into a viable mammal without a mother?


From Keith Robison: Senapathy has an explanation for [how a single cell could grow into an entire animal in any conceivable primal pond]. He postulates the formation of "seed cells" which develop into whole organisms, and the existence of lots of proteins in the primordial pond.

The major reason I haven't critiqued it is that it is so difficult to carefully criticize such a monstrous improbability. Where do you start? One obvious problem is that many ova contain molecular asymmetries laid down by the mother which are critical to symmetry-breaking during development. Also, mammalian chromosomes will not support development unless properly marked by methylation (imprinting). But in general, you are stuck arguing about hypothetical probabilities, and Senapathy's statistics are either wildly careless or dishonest (he basically leads off the book with a calculation which is off by many orders of magnitude because he forgot about the units involved).

"Could a mammalian reproductive cell really grow into a viable mammal without a mother?"

Nope. Not in a million years. Very, very few organisms know the trick of breaking symmetry de novo, and vertebrates certainly don't fall into this category.


From Arlin Stoltzfus: "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. 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).


From David W. Coutts: "Could a mammalian : reproductive cell really grow into a viable mammal without a mother? Nope. Not in a million years."

Careful! We are talking geological time-scales here! This was the post I have been waiting to see. Too much criticism of Senapathy has been based on molbio though. How about seeing the woods through the trees - What Senapathy says appears absurd as soon as you look at complete organisms. Not only the powerful arguments Keith raises above, but also Senapathy's hypothesis would be a dream for any creationist to debunk - all their illogical probability theories would actually apply here. It is nice that they worked out all those numbers, and at last someone has come up with a theory that they can fully disprove.

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. Does he really suggest that complete and well adapted organisms (and lots of "hopeless 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!


Keith Robison replies: The scary thing is you summarized his view in a nutshell. Senapathy believes this all took place in the sequence & timing indicated by the fossil record. Of course it is completely absurd! The main reason I beat on with molbio arguments is, well, I'm trained as a molecular biologist. It's also an interesting challenge to try and debate an idea which is SO bad -- as you wrote, just about everything is either far beyond the realm of plausibility (his theories) or completely wrong (his attacks on evolution).

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