"Genome Research" Theory Q&A: 2/4

Periannan Senapathy sena at genome.com
Fri Apr 7 08:43:27 EST 1995

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   I can tell that some of my critics have at least browsed the book,
but many of their comments indicate that they have not read it
completely, and/or very carefully, since they ask questions that are
specifically answered in the book.

   Keith Robinson (robison at mito.harvard.edu) writes:

   > In order to clear the decks, Senapathy first tries to show that
   > Darwinian evolution is simply impossible.  Pages 35-37 (and
   > again 157-9) attempt to prove that the transformation of one
   > gene into another by random point mutation would require a time
   > greater than the age of the earth.  This is founded on an
   > improper use of serial probabilities:  i.e. Senapathy is arguing
   > that the probability of finding two mutations in the same gene
   > is the product of the mutation rates (probabilities).  What this
   > analysis ignores is that mutations occur within populations, and
   > recombination can combine two such mutations onto a single
   > molecule.  In short, Senapathy's analysis assumes a serial
   > process, when in reality it is parallel.

   Keith thinks that point mutations occurring in a particular gene
in different individuals would converge into a single individual by
recombination of these various sequence changes through sexual
mating.  This is the usual argument given in general by molecular
evolutionists.  But when we scrutinize the probability for this
process to happen by means of random mutations, random recombinations
and crossing-over during meiosis, we see that it is simply improbable
for a new gene to evolve by this manner.  Molecular biologists have
calculated that the mutation rate is between one per million and one
per billion per nucleotide per generation.  This indicates a rate
estimate of one mutation in an average gene every 200,000 years (ref:
Alberts, B. et al, 1983, Molecular Biology of the Cell, Garland
Publishing, Inc., New York & London, page 214).  Multiple sequence
mutations that occur at different sequence positions in a particular
gene in various individuals of a population should all converge into
one single molecule--i.e. in one single individual.  Similar changes
have to occur in multiple genes and all these multiple changed genes
should converge into one individual, and this calculation should also
incorporate the very low meiotic DNA recombination rate.

   The probability for combining all this into one individual to have
any meaning in the process of evolution is astronomically low.  To my
knowledge no one else has done a systematic calculation anywhere in
the literature incorporating all the above to show how long it would
actually take for all the mutational mechanisms to converge all the
mutations into one single molecule (even taking all the parallel
changes).  Even if many different mutations would converge into a
single molecule, it would still be a variant of the original gene,
but not a new gene, when we take into account the biological
selection mechanisms.  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 (Richard Dawkins, ref above; and Bernd-Olaf
Kuppers, ref above, page 87), 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.

   Keith's next comment concerns gene-duplication:

   > Senapathy also provides explanations for how a number of
   > genome-modifying mechanisms cannot be significant contributors
   > to evolution.   His discussion of gene duplication claims that
   > this cannot be a significant contributor to evolution, because
   > if it were we should see enormous numbers of pseudogenes in the
   > genome (p.141).  This ignores the possibility of unselected
   > sequences being overwritten by other sequences.  Hence, under
   > evolutionary assumptions only recent pseudogenes are expected
   > to be detectable.

   By what molecular mechanisms does Keith mean that sequences are
being overwritten? By unequal crossing-over, point mutation,
gene-conversion, transposition?  By whatever means, if evolution of
new genes has to be achieved by tinkering with randomly duplicated
genes by random mutations within the duplicated genes, on statistical
basis we should see many, many more duplicated genes undergoing such
evolution than we see today in the genomes of living organisms. 
Again, if sequences are being overwritten, the inability of incipient
genes (a partially new gene in the process of formation of a fully
new gene) being selected would show that it is extremely improbable
to evolve new genes if unselected genes are being overwritten.  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.  In any event,
please note that Keith agrees that his explanation is offered "under
evolutionary assumptions."

   The reality is that the set of genes of any organism is
essentially constant.  A genome is changed by the many types of
mutations including point mutation and gene-duplication, but only to
change the intergenic junk sequences and introns to a great extent. 
Even the protein coding exons can mutate up to about 90% without
changing the structure or the function of the proteins they encode
(due to the high *tolerance* of every protein to amino acid sequence
variation)--all without evolving new genes or new organisms.  This
physical genetic-flux--occurring independently in distinct,
independently originated organisms--is mistakenly cited as the
molecular mechanism of evolution, but the evidence simply does not
support that conclusion.  These genetic changes *are* the cause for
the normal "individual variations" in the population of an organism. 
As I mentioned before, any other genetic change would only lead to a
defective organism, not to a new organism.

   Again from Keith Robinson:

   > The book is frequently internally inconsistent.  After spending
   > pages upon pages proving that it is impossible for developmental
   > pathways to evolve, he spends pages 344-346 explaining how they
   > must evolve.  The problem is this: under Senapathy's theory, not
   > only must whole genes arise from random sequence, but they must
   > have all the correct regulatory signals.  Similarly, after
   > spending many pages explaining how developmental-genetic
   > pathways are inviolate and cannot be modified significantly, he
   > spends pgs 347- 348 describing how different genes could be
   > assembled in different forms to produce different
   > developmental-genetic pathways.

   While I say that random mutations cannot evolve new genes by
organismal descent with modification (i.e. within the genomes of
living organisms), how do I say that new unique genes could simply
occur fully-formed in a primordial pond, so that they could
self-assemble into various genomes?  Again, I have devoted a whole
chapter to this specific question and giving a detailed answer:  The
occurrence of abundant genes in the primordial pond was inevitable.
And another chapter describes how these fully-formed genes simply
occurring in random primordial genetic sequences could self-assemble
to form many genomes nearly simultaneously.  Note that this
discussion is not molecular evolution within the organisms, as Keith
has misunderstood.  The two phenomena are entirely distinct and their
probabilities are monumentally different.

   In fact, I describe detailed computational analyses to show that
fully formed split-genes (which are typical of all the eukaryotes,
including all multicellular animals and plants) could simply occur in
a small finite amount of random DNA in a primordial pond. During my
work towards understanding the processes by which genes could occur
fully-formed and by which genomes could be self-assembled, I worked
out the details as to why it is extremely probable for eukaryotic
genes to occur in random primordial DNA sequences, and why it is
simply improbable for prokaryotic genes to occur in these sequences.  
Note also that all the structural features of genes predicted by this
theory (by computer simulation analyses of genes) are precisely and
completely found in almost all of today's living organisms.  This
theory on the origin of split-genes, published in two separate
articles in the PNAS, has also been commended in New Scientist.  
(You can now read these New Scientist articles in my web page: 

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