"Genome Research" Theory Q&A: 1/4

Periannan Senapathy sena at genome.com
Fri Apr 7 08:38:33 EST 1995


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   Since I posted my original announcement of this new theory few
weeks ago, many good questions have appeared in various forums
pertaining to evolution, molecular biology and paleontology.  I am
happy to respond to them here collectively.  Keith Robinson, Andrew
McRae, Tom Holroyd and Greg Buchannan have asked particularly
insightful questions, and I thank them--and everyone--for their
interest and thoughtful contributions to the discussion.

   Before answering specific questions, I would like to restate the
two primary objectives of my book.  In the first part, I believe I
have shown that no known mechanism of genetic mutation can evolve new
genes for unique protein functions or new developmental genetic
programs (DGPs) for unique body parts in any multicellular organism. 
Please note that the simplest single cell, assumed to be the ancestor
of all life on earth, is supposed to have given rise to all these
organisms purely by random mutational mechanisms.  I have devoted an 
entire chapter of the book (96 pages, 103-199) to a detailed analysis
of all these mutational mechanisms--from transposition, crossing-over
and exon-shuffling to the different types of gene-duplication,
chromosomal aberrations, DNA recombination, point mutation,
pleiotropy and  others--and an assessment of their ability to evolve
new genes and new genetic networks.  The analyses show that these
mechanisms can easily produce a huge repertoire of normal variants of
each gene, and can produce defective genes, but can never produce a
qualitatively new gene or a new DGP.  The many normal variants of a
particular gene prove only that the protein coded by that gene is
*tolerant* to many amino acid sequence variations, without changing
its fundamental structure or its biochemical function.  Defective
genes can lead to congenital and genetic disorders and cancer.  But
none of these mechanisms can produce a new gene or a new anatomical
structure, and therefore genetic mutations cannot produce new, unique

   From these analyses I conclude that genetic mutations are an
innate and unavoidable biochemical property of the DNA molecule and
genes, and exist in the genomes of distinct organisms without
changing the constancy of the set of genes or the fixity of the DG
pathway of the genome of every distinct organism.  That is, even if
numerous distinct organisms had originated by independent assembly of
their genomes from a common pool of genes in a primordial pond, the
very same set of genetic mutations and rearrangements would exist in
these independently originated organisms--simply changing the
physical nature of the genome, but not its constant set of genes or
its DGP.  The large amount of junk DNA sequences between genes and
the intronic junk sequences within genes would be changed, and even
the physical positions of genes within chromosomes, but not the genes
themselves (except to their normal variants), nor the genetic
networks in which these genes are organized.  This notion that such
genetic changes are evidence of ongoing molecular evolution has
simply been uncritically accepted, but in fact these changes are only
physical, not functional.  Please note that no systematic scientific
analysis of this pervasive assumption -- scrutinizing all the known
mechanisms of genetic mutation and rearrangement -- has even been
attempted until now.

   In the second part of the book, I explain in great detail how the
genomes of all distinct organisms could have occurred independently
in the primordial pond.  The common belief is that it is highly
improbable for even one gene to arise at random, purely by chance, in
the primordial pond's random genetic sequences (ref:  Monod J, 1970,
Chance and Necessity, 1972 edition, Vintage Books, New York; Dawkins
R, 1986, Blind Watchmaker, WW Norton, New York, p 46; Kupper B,
Information and the Origin of  Life, 1990, The MIT Press, Cambridge,
Mass, pp 59-62).  In fact they say that even a short gene would have
been utterly improbable even in a mass of DNA equal to the mass of
the whole universe.  But since life on earth is a reality, they
simply assume that the first primitive ancestral living cell occurred
by some improbable freak accident.  Moreover, this presumed
improbability of genes and life directly from inanimate matter is
cited as evidence that all life diverged from just that one primitive
ancestral cell.  No evolutionist that I know of--and I have searched
hard--has ever proposed a mechanism for the origin of the genes and
genome of the first cell.  Even modern evolutionists do not explain
the origin of the first cell, and begin their explanation assuming
that the first ancestral cell "somehow" originated on earth.

   But to the contrary, my research shows that the chance occurrence
of multitudes of genes was actually inevitable in a small primordial
pond.  The main difference between the previous computations and my
own is that my analyses incorporate the structural features of
eukaryotic genes--namely their split exon-intron architecture--which
is perhaps the most crucial factor in these analyses.  My approach
also incorporated other important insights into gene and protein
structures, such as codon degeneracy and amino acid degeneracy.  My
research, using actual DNA and protein sequences of the genes of
living organisms from the DNA and protein sequence databanks (the
GenBank and the Protein Information Resource), and many types of
computer simulations, demonstrates that fully formed genes could
exist abundantly in a reasonable amount of random genetic sequences
that could be available in a primordial pond.  In fact, an entire
chapter of the book (72 pages, 221-293) is devoted to a systematic
derivation of this premise.

   Accommodating the split-gene architecture--now generally
acknowledged to be a fundamental feature of genes--in these
calculations and analyses really changes everything.  Please note
that this has never been done so far, since its discovery in 1978. 
With this new evidence, it becomes apparent that numerous split-genes
were indeed statistically inevitable within only a small amount of
DNA--and certainly within the DNA expected to be available in a
primordial pond.  And if we can establish the origin of numerous
fully formed genes in a primordial pond, it then becomes entirely
plausible that many fully formed genomes formed spontaneously, by a
sort of random "mix and match" process.

   Chapters 6, 7 and 8 of the book provide ample evidence to conclude
that primordial Earth's rich biochemical environment contained all of
the enzymes necessary to facilitate the combination and recombination
of genes and multi-gene segments into complete genomes.  Of course,
only a tiny fraction of the genomes thus formed were at all viable,
and those that were meaningless would never have found expression as
organisms.  But again, statistical models demonstrate that so many
billions of prototype genomes were likely to have been formed in this
way, that many millions of them would have been viable and

   I know that my conclusions are at odds with what scientists in
many disciplines have believed for a very long time, and I must say
that I fully expected this controversy, as well as much of the
sarcasm and name-calling.  But my conclusions are drawn from a series
of related premises that I have developed or verified by my own
research and by the published and accepted work of others.  My own
findings include:
  1) The complex-looking eukaryotic genes are astronomically far more
     probable to have spontaneously occurred than the simpler-looking
     prokaryotic genes, and that the eukaryotic genes did occur first
     on earth (PNAS, 83:2133-2137; PNAS, 85:1129-1133).
  2) Not one but millions of genes can spontaneously occur fully
     formed in the random DNA sequence pool in the primordial pond.
     In fact, this is probabilistically inevitable (my book pages
  3) The complex-looking eukaryotic cell is far more probable than
     the prokaryotic cell with simpler morphology (my PNAS articles,
     refs above).
  4) The genomic structural complexity of complex multicellular
     organisms is not much greater than for the simplest single-
     celled eukaryotes, so the spontaneous assembly of genomes from
     a large pool of available genes is no more nor less difficult or
     likely for any particular organism, regardless of its
     morphological complexity.

   Being basically a molecular biologist and an ardent evolutionist
myself for many years, I am fully aware of the genetic and cellular
similarities among widely varying organisms, and how evolutionary
biologists would interpret them.  But, my theory of the common origin
of the genomes of many distinct organisms from a common pool of genes
in one primordial pond is able to explain these similarities well. 
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.
   In parts 2 through 4 of this post I will respond to specific
comments and questions from forum participants.

[Continued .....]

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