=== INDEPENDENT BIRTH OF ORGANISMS: === === A SYNOPSIS OF THE THEORY === Copyright 1994 by

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=========================================== =========================================== === INDEPENDENT BIRTH OF ORGANISMS: === === A SYNOPSIS OF THE THEORY === =========================================== =========================================== Copyright 1994 by Periannan Senapathy, Ph.D. All rights reserved. *************************************************************** *** NOTE: Derivations of critical premises (marked by * ) *** *** are explained and documented under separate subtitles *** *** following the theory Summary. *** *************************************************************** *************************************************************** *** NOTE: Exponential notations within this ASCII-text *** *** file are denoted by the ^ character, as in: "10^26" *** *** (which means "ten to the twenty-sixth power"). *** *************************************************************** SUMMARY ======= New research and recent advances in our understanding of genome mechanics, DNA sequence structure and genetic mutations all indicate that the genome of an organism is much more rigid than previously believed. In fact, all genomes seem to be essentially fixed and immutable to substantive, evolutionary- scale changes, even over geologic time.* A few adaptive mutations seem statistically plausible, but a distinct organism's characteristic morphology and biochemistry now appear to be permanently closed to the development of any new organ, appendage or biochemical process. The implications of this hypothesis are staggering, since it refutes the fundamental premise of virtually all theories of species evolution, which have prevailed in one form or another since Charles Darwin articulated the original theory in 1859. All evolution theories hold that all species have descended from one or only a few primitive single-celled ancestors in the proverbial primordial pond, and that the rich variety of life forms on Earth is a product of natural selection. But if genomes are indeed fixed and immutable, then natural selection can produce only incidental variations among essentially similar species, and therefore can explain only a small fraction of the diversity of life on Earth. If genomes are fixed and immutable, then most of Earth's plant and animal species must have originated independently in the primordial pond. This dramatic finding is clearly at odds with existing research that purports to demonstrate, mathematically, that the random formation of even a single gene from primordial chemical components would have been virtually impossible. But those statistical models predate the 1978 unveiling of the structural features of eukaryotic genes (those in plants and animals), and other, newer derivative insights into the molecular structure of DNA and genes. When this current data is processed by more advanced statistical-analysis methods and modern computing tools, the earlier assessments are seen to have suffered from invalid premises and fatally simplistic computations. New research and computer simulations now show that the interactions of increasingly complex chemical compounds in a rich primordial broth, under a broad range of extreme catalytic conditions and over geologic time, spontaneously produced an abundance of very long, random DNA sequences.* And further studies based on these findings, and on our new comprehensive understanding of DNA and gene molecular structures, now confirm that indeed many fully formed genes almost certainly occurred naturally, entirely by chance, within the long, random primordial DNA strands. In fact, the total mass of DNA in the primordial pond seems to have been entirely sufficient to have made the natural occurrence of billions of genes statistically inevitable.* Meanwhile, other recent published studies have demonstrated that, contrary to what biologists had long believed, eukaryotic organisms actually preceded prokaryotes on Earth*, despite the greater length and complexity of eukaryotic vs. prokaryotic genes. This new knowledge may at first seem inconsistent with an abundance of naturally occurring genes in primordial DNA, since the greater length and complexity of eukaryotic genes would seemingly make them less likely to occur by chance. But systematic analyses reveal, surprisingly, that the structural features of eukaryotic genes actually made them much MORE likely than prokaryotic genes to occur within random DNA sequences.* If genes did indeed form spontaneously, and abundantly, in the primordial pond, then we are free to return to the same astonishing conclusion: that most of Earth's plant and animal species originated independently in the primordial pond. A twelve-year investigation into this possibility has uncovered a strong likelihood that the random assembly of vast numbers of available genes in the primordial pond actually produced innumerable multi-gene DNA segments, which in turn combined and recombined to form billions of complete genomes.* Of the multitudes of genomes thus formed, most were meaningless and perished instantly, but the millions of organisms coded by viable genomes became prototypes for the myriads of life forms that walk, swim, fly and flower over the Earth today. Scientists have long been troubled by conspicuous evidence that contradicts evolution theories, including prominent gaps in the fossil record, the "Cambrian explosion," and the complexities of advanced organ systems, which many scientists concede are unlikely to have occurred by natural selection. But the basic theory has persisted, year after year, in the absence of any plausible alternatives. To be sure, scientists continue to debate various aspects of the theory, and some remain unconvinced that natural selection, at least as articulated by Darwin, is the sole or even the primary mechanism of evolution. But the critical premise of all evolution theories--that all life on Earth diverged from a single primordial organism, or from just a few--seems to be regarded as beyond reproach. Given our cultural environment, it is understandable that much of the evidence that contradicts evolution has been simply ignored, while other evidence has been misinterpreted to falsely corroborate evolution theory. Taxonomists, for example, have long pointed to superficial morphological similarities among dissimilar organisms as evidence that they diverged from a common ancestor. Invertebrates contain body fluids that resemble vertebrate blood in both viscosity and function (if not color), and it is therefore only natural to assume that invertebrate "blood" is a very distant cousin to our own. Invertebrates also exhibit respiratory, digestive and endocrine systems, and structural features such as eyes, and what we call "mouth parts," and "arms" and "legs," so it seems entirely plausible that our own ancestors mutationally branched off from invertebrates not too far from the shores of the primordial pond. But most taxonomists are not molecular biologists. And molecular biologists have now determined that the vertebrate genes and invertebrate genes for most seemingly comparable organ systems, structural features and biochemical processes are utterly dissimilar. The development, composition and functionality of human blood, for example, is governed by more than 600 genes, but not one of them has yet been found to be even remotely similar in molecular structure to any of the known genes that code for invertebrate "blood." If all life on Earth had descended from a common ancestor, then we would surely expect to find recurring patterns of structural similarities among different organisms' genes for comparable morphological and biochemical features. This expectation has become even more compelling in light of our newly sophisticated understanding of genes' molecular structures, and researchers have searched hard for this molecular evidence that would corroborate evolution theory. But much to the surprise of confirmed evolutionists who have tried, absolutely no evidence of evolutionary relatedness has yet been found in exhaustive comparisons of the structural features of dissimilar organisms' genes for "blood"; or for comparable biochemical processes such as coagulation; or for comparable metabolic systems such as respiration, immunity and other systems. Only a few isolated single-gene similarities have been identified, and these do not even begin to constitute the sort of systematic pattern that we would expect to find in organisms sharing a common ancestry. Indeed, the disjointedness of the gene similarities corroborates instead the "mix-and-match" scenario of random, independent genome assembly from a rich gene pool in the primordial pond! These investigations into comparative gene structures have also helped to confirm an insightful new conclusion drawn from mostly existing evidence: that despite the enormous morphological differences across the full spectrum of life on Earth, the level of genomic COMPLEXITY varies very little among different organisms, even between single-celled eukaryotic microbes and the so-called higher multicellular organisms. Genomic complexity--if measured by complexity of molecular structural features, or functional complexity of genomic expression in the developmental genetic (DG) pathway--is remarkably constant among all eukaryotic organisms. Moreover, genome length simply does not correlate to morphological or biochemical complexity. We humans are clearly more complex than amphibians, for example, and yet many amphibian genomes are 50 to 100 times longer than the human genome. The random assembly of genomes for the simplest life forms would therefore have been no more nor less likely, probabilistically, than for morphologically complex organisms, and this finding notably eliminates any need to explain an incremental simple-to-complex evolution of organisms. If Earth's contemporary organisms did in fact originate independently from genomes assembled in the primordial pond, then some mechanism must have facilitated the expression of primordial genomes into the first plants and animals. The recent revelation that Earth's first cells must have been unicellular eukaryotes, rather than simpler bacteria as previously believed, points to one such plausible mechanism, logically derived from what we know and can infer about the primordial environment. The development of the first organisms from viable genomes may well have been facilitated by intermediary "seed cells": eukaryotes whose structures and functions resembled the fertilized egg cells of contemporary multicellular organisms. A generation ago evolution theory easily survived Watson and Crick's extraordinary revelations of DNA structure and function, and subsequent researchers' characterizations of genetic mechanisms at the molecular level. These insights, however, did not prove evolution any more than they debunked it; they simply coexisted with the still unproven theory. But evolution theory will not be so lucky in the wake of contemporary genome research. "Independent Birth of Organisms" easily explains all of the available evidence--molecular, biochemical, organismal and fossil--and notably accommodates all of the contra-evolution evidence that has dogged evolutionists since Darwin. DERIVATIONS OF CRITICAL PREMISES ================================ Genomes are Essentially Fixed and Immutable ------------------------------------------- Every organism's characteristic morphology and biochemistry are manifestations of specific proteins whose structures, functions and chemical compositions are coded by the organism's genes. Moreover, specific gene-coded proteins also define, for every organism, a unique developmental genetic (DG) pathway that governs the selective and sequential expression of other genes in both the embryonic development of the organism and the ongoing maintenance of its biochemical functions. The evolution of any organism into a new, different organism would therefore require the genetic alteration of some proteins into entirely new proteins. But probabilistically, no known mutation mechanism can produce even a single new gene for an entirely new biochemical or biological function, or for a new organ or appendage, or for a new branch to the DG pathway. Genetic mutations are known to occur at an extremely low rate: roughly one mutated DNA character per generation within a DNA strand of 10^6 to 10^9 nucleotides. Within a given gene, this low frequency of mutations can easily produce many normal variants without affecting the specific biological function of the corresponding protein. But the genetic alteration of a protein's function would almost certainly require at least a full 1% SPECIFIC change in the gene's coding sequence, and the low mutation rate combined with the required specificity make such a change astronomically improbable, even cumulatively over trillions of years. New research documented in "Independent Birth of Organisms" demonstrates that mutations affecting a protein's crucial amino acids can produce only protein defects, which in turn typically produce metabolic defects, congenital diseases and cancer. Such mutations cannot, however, alter the characteristic function of a given protein over any span of geologic time. Chapters 3 and 4 of "Independent Birth of Organisms" provide detailed analyses of published and accepted data to assess the probabilities of various possible combinations and permutations of the nine primary classes of genetic mutations and rearrangements, and of mutation frequencies. These investigations all point to the same conclusion: that genetic mutations and rearrangements can produce only normal individual variations, changes in incidental characteristics such as coat color and stature, and metabolic and genetic diseases. The many variant species of snails, for example, may well have evolved by natural selection from a single snail ancestor. But the probability of one organism genetically mutating into an entirely new organism, even gradually over many generations, is virtually nonexistent. Long, Random DNA Sequences Occurred Spontaneously in the Primordial Pond --------------------------------------------- All evolution theories depend on the premise that one or only a few primitive organisms emerged from the primordial pond. That fundamental premise rests in turn on a mathematical assessment of the chances that any organism could have emerged from the random chemical reactions in the primordial pond. Statistically, say evolutionists, the random assembly of primordial components into even a single primitive genome would have been virtually impossible, so the origin of the first organism--even of the simplest single-celled microbe--can be explained only by some fantastically improbable accident. But that assumption is contradicted by new evidence obtained by the unprecedented application of sophisticated statistical-analysis methods and modern computing tools to new insights into molecular genetics and the specialized field of chemical evolution. "Independent Birth of Organisms" asserts that multitudes of complete genomes occurred spontaneously in the primordial pond, but this fundamental premise is actually a conclusion drawn from a three-link chain of evidence. The spontaneous formation of complete genomes would have required the existence of an enormous "gene pool": a pooled source of available genes and multi-gene segments that could combine and recombine to form the various genomes. The existence of a viable gene pool depends in turn on the primordial existence of an adequate supply of random DNA sequences that were long enough to contain, entirely by chance, a sufficient number of genetically meaningful segments--what we call "genes." And the existence of such long, random DNA sequences in the primordial pond depends on the probability that such sequences formed spontaneously from primordial chemical compounds mixing over a specific period of time in the primordial environment. Each of these links in the evidence chain is explained separately and in more detail below, and is fully documented in the book-length articulation of the theory. Recent research and consultations with world authorities in chemical evolution support an inference that Earth's primordial ponds contained enormous quantities of long, random DNA sequences. In fact, chapter 6 of "Independent Birth of Organisms" provides fairly simple mathematical calculations to illustrate how the primordial pond probably yielded and supported DNA strands totalling 10^26 nucleotide molecules. By contrast, the DNA of the human genome contains roughly 10^9 nucleotide molecules--which is 10^-17 = 1/100,000,000,000,000,000 the length of the random sequences that probably occurred in the primordial pond. Chapter 6 explains the chemical processes and primordial conditions that permitted and even encouraged the formation of these long, random DNA strands within the primordial pond. Fully Formed Genes for Multicellular Animals and Plants Occurred Spontaneously Within Primordial DNA Strands ----------------------------------------------------------- Statistically, random DNA sequences extending to a combined length of 10^26 (100,000,000,000,000,000,000,000,000) nucleotide molecules would certainly contain many billions of the genetically meaningful segments we call "genes." The probabilistic analysis appears in chapter 7 of "Independent Birth of Organisms." Analyses of the structural and functional features of multicellular organisms' genes and proteins, and computer simulations based on them, reveal that the natural occurrence of an abundance of fully formed genes within primordial DNA was not only possible, but probabilistically inevitable. The 1978 discovery of eukaryotes' split-gene architecture, and recent research showing that eukaryotic genes actually preceded prokaryotic genes (contrary to what biologists had long believed--see separate topic below), both radically alter the equations used to determine whether fully formed genes could have occurred spontaneously within primordial DNA strands. Previous attempts to assess that likelihood predated these revelations, and also failed to incorporate the degeneracy of amino acids in protein sequences, and the degeneracy of codons in genes as potent factors in the calculations. New computer simulations, documented in chapter 7 of the book, confirm that virtually any gene that codes for proteins with almost any biochemical function could occur directly in its split-gene form in the primordial genetic sequences. Moreover, almost all of the structural features of genes predicted by these probabilistic models and simulations are indeed found to exist in almost all known genes of living animals and plants. Multitudes of Complete Genomes for Complex Multicellular Animals and Plants Occurred Spontaneously in the Primordial Pond ---------------------------------------------------------------- The breakup of primordial DNA strands and recombination of segments to produce genetically meaningful sequences, multi-gene segments and complete genomes would have required a viable mechanism to induce and facilitate such recombinations. Chapters 6, 7 and 8 of "Independent Birth of Organisms" explain, specifically and in depth, the mechanisms by which individual genes and multi-gene segments in the gene pool could have easily combined and recombined to form multitudes of complete genomes. These chapters provide ample evidence to conclude that primordial Earth's rich biochemical environment provided all of the enzymes necessary to facilitate the combination and recombination of genes and multi-gene segments into complete genomes. Eukaryotes Preceded Prokaryotes ------------------------------- Biologists have long believed that prokaryotes must have preceded the "evolution" of eukaryotic organisms, since eukaryotes are morphologically more complex than prokaryotes, such as bacteria, whose cells contain no nucleii and whose genomes consist of short but contiguously sequenced genes. Even after the 1978 discovery of eukaryotes' split-gene architecture, biologists believed that the chance occurrence of eukaryotes' longer genes within primordial DNA would have been virtually impossible. But exhaustive statistical analyses of all known gene sequences, in all organisms, have now shown that it was the split genes of eukaryotes that actually occurred first in the primordial DNA. As noted above, the structural features of eukaryotic genes actually made them MORE likely than prokaryotic genes to occur within randon DNA sequences. This finding was published in 1986 in the Proceedings of the National Acadamy of the Sciences. A continuation of this research, published in PNAS in 1988, documented how the genes of all plants and animals, including single-celled organisms, all exhibit precisely the same features of genes that were predicted by the original analyses. Still more research into this same topic, published in Nucleic Acids Research, Molecular Genetics and Methods in Enzymology, has yielded even more supporting evidence. CREDENTIALS OF DR. PERIANNAN SENAPATHY, AUTHOR OF "INDEPENDENT BIRTH OF ORGANISMS" ========================================== Professional History -------------------- 1990-Present: President & CEO, Genome International Corporation: Developing computational analysis tools and services for genome research. 1987-1990: Associate Scientist, University of Wisconsin Madison Biotechnology Center and Department of Genetics: Continuation of research begun at NIH 1984-87 (see below). 1984-1987: Visiting Associate, National Institutes of Health, Division of Computer Research and Technology, Laboratory of Mathematical and Statistical Methodology: Research into computational algorithms, database applications and computer graphics for genome mapping, sequencing and protein analysis, and their integration into software. 1980-1984: Visiting Fellow and Visiting Associate; National Institutes of Health; National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases; Laboratory of Molecular and Cellular Biology. Research into gene expression and regulation, genetic recombination, and DNA replication in human systems. Education --------- Ph.D., Indian Institute of Science (Bangalore, India), 1979: Graduate training in biochemistry, molecular biology, statistics and human physiology. Awarded Gold Medal for best Ph.D. thesis in biological sciences division. M.S. Biochemistry, Molecular Biology, and Human Anatomy and Physiology, 1972: University of Madras (Madras, India). B.S. Chemistry, Math and Physics, 1970: Loyola College (Madras, India). Selected Publications --------------------- P. Senapathy, and T.M. Jacob (1981): Identification and purification of tRNAs containing N^6-(Delta^2-Isopentenyl) adenosine using antibodies specific for N^6-(Delta^2- Isopentenyl) adenosine. Journal of Biological Chemistry 256:11580-11584. P. Senapathy, Jon Duri-Tratschin and B.J. Carter (1984): Replication of Adeno-associated virus DNA: Complementation of naturally occurring rep mutants by wild-type genomes or an ori mutant and correction of terminal palindrome deletions. Journal of Molecular Biology 179:1-20. P. Senapathy and B.J. Carter (1984): Molecular cloning of Adeno- associated variant genomes and generation of infectious virus by recombination in mammalian cells, Journal of Biological Chemistry 259:4661-4668. P. Senapathy (1986): Origin of Eukaryotic Introns: A hypothesis, based on codon distribution statistics in genes, and its implications, Proceedings of the National Academy of Sciences USA 83:2133-2137. M.B. Shapiro and P. Senapathy (1986): Automated preparation of DNA sequences for publication, Nucleic Acids Research 14:65-73. M.B. Shapiro and P. Senapathy (1987): RNA splice junctions of different classes of eukaryotes: Sequence statistics and functional implications in gene-expression, Nucleic Acids Research 15:7155-7175. P. Senapathy (1988): Possible evolution of splice-junction signals in eukaryotic genes from stop codons, Proceedings of the National Academy of Sciences USA 85:1129-1133. P. Senapathy (1988): Distribution and repetition of sequence elements in eukaryotic DNA: New insights by computer aided statistical analysis, Molecular Genetics (Life Sciences Advances) 7:53-65. P. Senapathy, M.B. Shapiro, and N. Harris (1990): 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." R.F. Doolittle, Ed. 183:252-278. N. Harris and P. Senapathy (1990): Distribution and consensus of branch point signals in eukaryotic genes: A computerized statistical analysis, Nucleic Acids Research 18:3015-3019. P. Senapathy (1994): Independent Birth of Organisms. Genome Press, Madison, WI. J.J. Puthukattukaran, S. Chalasani and P. Senapathy (1994): Design and implementation of parallel algorithms for gene- finding. Proceedings of the Third International Symposium on High Performance Distributed Computing (in press). P. Senapathy (in preparation): Computer analysis of gene structure and function. ͻ ۺ ۺ INDEPENDENT BIRTH OF ORGANISMS ۺ ۺ by Periannan Senapathy, Ph.D. ۺ ۺ ۺ ۺ hardcover * 656 pgs * $29.95 ۺ ۺ Genome Press, Madison, WI ۺ phone 1-800-204-4332 ۺ ͼ

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