Human Genome Search at University of Oklahoma
What'sNEW pertaining to the human genome in general

The objective of the research is to use bioinformatic analysis of genomic data to address the question "Is sustained macroevolutionary progress possible in a closed system?". In the context of genomics, we believe that we can gain insights into this question by studying the origin and evolution of gene families.

By definition, "species" of higher organisms (especially animalia) are considered to be genetically closed systems. Conventional Darwinian thinking is that most or all gene families arise through gene duplication and divergence. Strong panspermia suggests that all or most gene families enter a species lineage by horizontal transfer from other species, with these new genes ultimately arriving from outer space.

The current phase of the research will have as its primary target, the quantitative estimation of the relative proportion of new genes and gene families arising by duplication/divergence or by horizontal transfer. If this work demonstrates a significant proportion of horizontal transfer, we will publish this result and acknowledge that it is surprising to Darwinians, but predicted by the strong version of panspermia. Then we will develop a new phase that considers all possible sources for the genes.

The study of the evolution of gene families will begin with a comparison of the human and mouse genomes, to identify a set of genes and gene families present in humans, but absent in mice. This will be followed by a targeted search for these gene families in every available genome between the human and mouse. This will give us the first clear picture of the process by which new gene families emerge and evolve.

Currently, there is no other genome available between the human and mouse, but we expect many to be completed in the coming years, with the greatest concentration of available genomes among the primates, which should be ideal for this study.

However, to avoid having to wait for full genomes to become available, we will attempt to raise funds for a targeted sequencing of the candidate gene families (from the human-mouse comparison), in every species between human and mouse for which BACs are available.

In spite of the limitations on the availability of genetic data, we believe that there is certainly enough data available to begin work, and maintain momentum for a year or two. If we find ourselves in the position of having to wait for data, we would reduce or suspend the funding until the relevant data becomes available.

Tom Ray

In the first year, we anticipate the following activities:

1. The continued training of Tom Ray in the use of bioinformatic techniques
2. The selection, purchase, assembly, and development of administrative skills of a new linux cluster for bioinformatic analysis
3. Development of analytical protocols for addressing the questions of this study.
   • a) How to define and recognize "gene families"
   • b) How to compare human and mouse genomes to recognize gene families present in humans but not mice
   • c) How to target the search for these gene families in the intermediate genomes as they become available
   • d) How to detect the emergence of new genes and gene families by duplication and divergence
   • e) How to detect the emergence of new genes and gene families by horizontal transfer
   • f) How to clearly discirminate between duplication/divergence and horizontal transfer
4. Application of the protocols to address the questions of this study
   • a) Comparison of mouse and human genomes to identify genes and gene families present in humans but absent from mice
   • b) Attempt to locate genes in the human genome which arose recently through duplication and divergence
   • c) Attempt to locate genes in the human genome which arose recently through horizontal transfer
   • d) Steps b and c can be repeated for any higher organism whose genome has been completed (e.g., mouse, drosophila)

While we can not make commitments for others, we hope that in the first year, a collaborative proposal can be developed and submitted, to target sequence the relevant gene families in many species.

We expect that all or most of the work described above can be started in the first year. However, it is notoriously difficult to predict research progress. Proposals tend to be ambitious, and research tends to take longer than anticipated.

If the reseach should reveal a significant frequency of horizontal gene transfer among higher organisms, we anticipate that Tom and Brig will coauthor a publication revealing this result.

What'sNEW (Also see Sequencing the Genome under "Can The Theory Be Tested?")

Researchers Find Human Virus in Chimpanzees, by Jeffrey Douglas, Virginia Tech News, 4 Jun 2008.
Jeffrey M. Kidd et al., "Mapping and sequencing of structural variation from eight human genomes" [abstract], doi:10.1038/nature06862, p 56-64 [also commentary by Evan Eichler, p xii] v 453, Nature, 1 May 2008.
Graham Coop et al., "High-Resolution Mapping of Crossovers Reveals Extensive Variation in Fine-Scale Recombination Patterns Among Humans" [abstract], doi:10.1126/science.1151851, p 1395-1398 v 319, Science, 7 Mar (online 31 Jan) 2008. "...Recombination rates vary tremendously across the human genome, with most events occurring in narrow 'hotspots.'"
Elliott H. Margulies and Ewan Birney, "Approaches to comparative sequence analysis: towards a functional view of vertebrate genomes" [open access login], doi:10.1038/nrg2185, p 303-313 v 9, Nature Reviews Genetics, Apr 2008.
Human Evolution Is Speeding Up, by Ann Gibbons, ScienceNow Daily News, 10 Dec 2007.
Michele Clamp et al., "Distinguishing protein-coding and noncoding genes in the human genome" [abstract], 10.1073/pnas.0709013104, Proc. Natl. Acad. Sci. USA, online 26 Nov 2007. "...The results indicate that there has been relatively little true innovation in mammalian protein-coding genes."
19 Nov 2007: Ancient retroviruses spurred evolution of gene regulatory networks in humans and other primates.
Adam Siepel et al., "Targeted discovery of novel human exons by comparative genomics" [abstract], 10.1101/gr.7128207, Genome Research, online 7 Nov 2007. "Despite these challenges, we have found evidence for thousands of novel exons corresponding to hundreds of genes."
Jan E. Janecka et al., "Molecular and Genomic Data Identify the Closest Living Relative of Primates" [abstract], 10.1126/science.1147555, p 792-794 v 318, Science, 2 Nov 2007.
25 Oct 2007: You can think of the genome as a revolving door—genes keep coming and going — Matthew W. Hahn
Thomas R. Gingeras, "Origin of phenotypes: Genes and transcripts" [abstract | PDF], p 682-690 v 17, Genome Research, 6 Jun 2007. "...Transcripts may be used to define the operational unit of a genome."
Erika Check, "Help flies in for human genome" [text], 10.1038/447361a, Nature, online 23 May 2007. "Genes are regulated by complicated networks that span huge portions of the genome...and... scientists don't fully understand some of the regulatory motifs that they have been studying for years."
Elizabeth Pennisi, "Working the (Gene Count) Numbers: Finally, a Firm Answer?" [summary], p 1113 v 316, Science, 25 May 2007. "The real answer is 20,488 [human genes] ...with perhaps 100 more yet to be discovered."
Human evolution, radically reappraised, World Science, 26 Mar 2007. "...The origin is still ongoing."
Margaret A. Bakewell et al., "More genes underwent positive selection in chimpanzee evolution than in human evolution" [abstract], 10.1073/pnas.0701705104, Proc. Natl. Acad. Sci. USA, online 20 Apr 2007.
The origin of the brain lies in a worm, European Molecular Biology Laboratory, 20 Apr 2007. "Researchers discover that the centralised nervous system of vertebrates is much older than expected."
"Special Online Collection: The Macaque Genome" [link], v 316, Science, 13 Apr 2007.
29 Mar 2007: I felt sick to my stomach.... — Jonathan Eisen
Chris P. Ponting and Gerton Lunter, "Human brain gene wins genome race" [PDF], p 149-150 v 443, Nature, 14 Sep 2006.
John K. Pace, II and Cédric Feschotte, "The evolutionary history of human DNA transposons: Evidence for intense activity in the primate lineage" [abstract], 10.1101/gr.5826307, Genome Research, online 5 Mar 2007.
31 Dec 2006: Many genes once thought to be unique to humans have been in the tree of life for over a half billion years.
Human-chimp genetic difference is as big as 6 percent, EurekAlert!, 21 Dec 2006.
Richard E. Green et al., "Analysis of one million base pairs of Neanderthal DNA" [abstract], 10.1038/nature05336, p 330-336 v 444 Nature, 16 Nov 2006.
28 Nov 2006: Did the acquisition of an advantageous gene improve human brains?
Neandertal DNA Comes to Life, by Elizabeth Pennisi, ScienceNOW Daily News, 15 Nov 2006.
Decoded sea urchin genome shows surprising relationship to man, EurekAlert!, 9 Nov 2006.
Feng-Chi Chen et al., "Human-specific insertions and deletions inferred from mammalian genome sequences" [abstract], 10.1101/gr.5429606, Genome Research, online 9 Nov 2006.
15 Sep 2006: Tom Ray replies to our open email of 31 Dec 2005.
Erika Check, "Mix and match: the hunt for what makes us human" [text], 10.1038/443008a, p 8-9 v 443, Nature, 7 Sep 2006.
Multiple copies of a mystery gene may make us human, doi:10.1038/news060828-5, by Erika Check, News@Nature.com, 31 Aug 2006.
Ryan E. Mills et al., "An initial map of insertion and deletion (INDEL) variation in the human genome" [abstract], 10.1101/gr.4565806, Genome Research, online 10 Aug 2006.
Geneticists shoot for Neanderthal genome in two years, doi:10.1038/news060717-13, by Rex Dalton and Nicola Jones, News@Nature.com, 20 Jul 2006.
Nick Patterson et al., "Genetic evidence for complex speciation of humans and chimpanzees" [abstract], 10.1038/nature04789, p 1103-1108 v 441, Nature, 28 Jun (online 17 May) 2006.
Jeffrey A. Bailey and Evan E. Eichler, "Primate segmental duplications: crucibles of evolution, diversity and disease" [executive summary], 10.1038/nrg1895, p 552-564 v 7, Nature Reviews Genetics, July 2006.
Elizabeth Pennisi, "Genomes Throw Kinks in Timing of Chimp-Human Split" [summary], p 985 v 312, Science, 19 May 2006.
Chimpanzee study reveals genome variation hotspots, EurekAlert!, 16 May 2006.
4 May 2006: A gene captured from a mobile element fused with another gene to make a new primate gene.
Gaby G. M. Doxiadis et al., "Reactivation by exon shuffling of a conserved HLA-DR3-like pseudogene segment in a New World primate species" [abstract], 10.1073/pnas.0600643103, p 5864-5868 v 103, Proc. Natl. Acad. Sci. USA, 11 Apr (online 31 Mar) 2006.
Most Human Chimp Differences Due To Gene Regulation Not Genes, TerraDaily.com, 9 Mar 2006.
Nicholas Wade, "Still Evolving, Human Genes Tell New Story" [link], The New York Times, 7 Mar 2006.
Natalay Kouprina, Adam Pavlicek, Ganeshwaran H. Mochida, et al., "Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion" [text: html], e126 v 2 n 5, PLoS Biol, May 2004.
A. Buzdin et al., "The human genome contains many types of chimeric retrogenes generated through in vivo RNA recombination" [abstract], p 4385-4390 v 31, Nucleic Acids Research, 1 Aug 2003. "These findings suggest that RNA-RNA recombination during L1 reverse transcription followed by the integration of the recombinants into the host genome is a general event in genome evolution."
24 Feb 2006: Retroposed genes have contributed to human evolution.
Researchers assemble second non-human primate genome, EurekAlert!, 9 Feb 2006.
Chris Tyler-Smith et al., "The rise and fall of the ape Y chromosome?" [abstract], 10.1038/ng0206-141, p 141-143 v 38, Nature Genetics, Feb 2006. "The sequence of a second chimpanzee Y chromosome ...reveals the recent gain of one [gene] on the human lineage...."
...Humans Have a Slow Molecular Clock, by Michael Balter, ScienceNOW Daily News, 23 Jan 2006.
18 Jan 2006: We hypothesize that these 'jumping genomic segments' ...[contribute] rapidly to primate gene evolution — Evan Eichler.
Brig Klyce solicits Tom Ray's current opinion on the original question in an open email, 31 Dec 2005.
Simon E. Fisher and Gary F. Marcus, "The eloquent ape: genes, brains and the evolution of language" [abstract], doi:10.1038/nrg1747, p 9-20 v 7, Nature Reviews Genetics, Jan 2006. "We argue that language should be viewed not as a wholesale innovation, but as a complex reconfiguration of ancestral systems...."
Eric T. Wang et al., "Global landscape of recent inferred Darwinian selection for Homo sapiens" [abstract], doi:10.1073/pnas.0509691102, Proc. Natl. Acad. Sci. USA, online 21 Dec 2005. "...1.6% of Perlegen SNPs were found to exhibit the genetic architecture of selection." Also see the following commentary:
Scoping Out Signs of Human Evolution, by Michael Balter, ScienceNOW Daily News, 20 Dec 2005. "...the team found some 1800 genes that appeared to have been under selection during the last 10,000 to 50,000 years."
Ajit Varki and Tasha K. Altheide, "Comparing the human and chimpanzee genomes: Searching for needles in a haystack" [abstract], doi:10.1101/gr.3737405, p 1746-1758 v 15, Genome Research, Dec 2005.
17 Oct 2005: The principal process by which new gene functions arise is by making use of preexisting genes — Roy J. Britten
30 Sep 2005: The chimp genome has been sequenced. At least seventeen human genes contain exons missing in chimps.
Robert Sean Hill and Christopher A. Walsh, "Molecular insights into human brain evolution" [abstract], doi:10.1038/nature04103, p 64-67 v 437, Nature, 1 Sep 2005.
Sarah J. Wheelan, Yasunori Aizawa et al., "Gene-breaking: A new paradigm for human retrotransposon-mediated gene evolution" [abstract], doi:10.1101/gr.3688905, p 1073-1078 v 15, Genome Research, Aug (online 15 Jul) 2005.
Fastest-evolving genes in humans and chimps revealed, by Jennifer Viegas, NewScientist.com, 3 May 2005.
Yinqiu Wang et al., "Accelerated Evolution of the PACAP Precursor Gene During Human Origin" [abstract], doi:10.1534/genetics.105.040527, Genetics, online 16 Apr 2005. Also see "Gene Sets Humans Apart," by Mason Inman, ScienceNow, 20 Apr 2005. "...A gene called the PACAP precursor stayed substantially the same across eons, but then,... evolved at warp speed in the human lineage."
Ingo Ebersberger and Matthias Meyer, "A Genomic Region Evolving Toward Different GC Contents in Humans and Chimpanzees Indicates a Recent and Regionally Limited Shift in the Mutation Pattern" [abstract], p 1240-1245 v 22 n 5, Molecular Biology and Evolution, May 2005. "...We suggest a recent and species-specific shift in the region's mutation pattern as the cause of its differing evolution in humans and chimpanzees."
Duplication Makes a New Primate Gene — a new CA webpage, 21 Feb 2005.
Priming the Human Primate, by Michelle Nhuch, Broad Institute, Astrobiology Magazine, 19 Feb 2005.
Hominids Lose Control (synopsis), doi:10.1371/journal.pbio.0030073, by Peter D. Keightley, Martin J. Lercher and Adam Eyre-Walker, v 3 n 2, Public Library of Science: Biology, Feb 2005 (online 25 Jan).
Ancestral Mammal's Genome Reconstructed, by David Grimm, ScienceNOW, 2 Dec 2004.
23 Nov 2004: Human genes composed mainly of mobile elements.
14 Nov 2004: The birth of a new gene unique to apes and humans....
Stéphanie Bertrand et al., "Evolutionary Genomics of Nuclear Receptors: From Twenty-Five Ancestral Genes to Derived Endocrine Systems" [abstract], p 1923-1937 v 21 n 10, Molecular Biology and Evolution, Oct 2004. "Our results imply that the genes for major receptors such as steroid receptors or thyroid hormone receptors were present in Urbilateria."
Takashi Angata et al., "Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms" [abstract], Proc. Natl. Acad. Sci. USA, online 26 Aug 2004.
UNC research accelerates discovery of novel gene function, by Adam Shutes, UNC School of Medicine, 6 Jul 2004.
Correspondence with Tom Ray... during the establishment and pursuit of this research project, 2001-2004.
16 Apr 2004: The rat genome has been sequenced.
David J. Amor et al., "Human centromere repositioning 'in progress'" [abstract], p 6542-6547 v 101, Proc. Natl. Acad. Sci. USA, 27 Apr 2004.
Erika Check, "Geneticists study chimp–human divergence" [text], p 242 v 428 Nature, 18 Mar 2004.
The Mouse Genome And The Measure of Man, National Human Genome Research Institute (NHGRI), Dec 2002.
Dennis M. Wilkinson and Bernardo A. Huberman, "A method for finding communities of related genes" [abstract], Proc. Natl. Acad. Sci. USA online, 2 Feb 2004.
Andrew G. Clark et al., "Inferring Nonneutral Evolution from Human-Chimp-Mouse Orthologous Gene Trios" [abstract], p 1960-1963 v 302, Science, 12 Dec 2003.
2003, November 20: In mammals, CNGs are more numerous and better conserved than genes.
Manyuan Long, Esther Betrán, Kevin Thornton and Wen Wang, "The Origin of New Genes: Glimpses from The Young and Old" [abstract], p 865 -875 v 4, Nature Reviews Genetics, Nov 2003.
Dog genome unveiled, Nature Science Update, 26 Sep 2003.
W. James Kent et al., "Evolution's cauldron: Duplication, deletion, and rearrangement in the mouse and human genomes" [abstract], p 11484-11489 v 100 Proc. Natl. Acad. Sci. USA, 30 Sep 2003.
Pioneering Study Compares 13 Vertebrate Genomes, NIH news Release, 14 Aug 2003.
J.W. Thomas et al., "Comparative analyses of multi-species sequences from targeted genomic regions" [abstract], p 788-793 v 424 Nature, 14 Aug 2003. "...Among the primates, large indels are the principal mechanism accounting for the observed sequence differences, a finding that is consistent with other studies...."
Jinxiu Shi et al., "Divergence of the genes on human chromosome 21 between human and other hominoids and variation of substitution rates among transcription units" [abstract], Proc. Natl. Acad. Sci. USA, 24 Jun 2003.
Tatsuya Anzai et al., "Comparative sequencing of human and chimpanzee MHC class I regions unveils insertions/deletions as the major path to genomic divergence" [text], p 7708-7713 v 100, Proc. Natl. Acad. Sci. USA, 24 Jun 2003.
2003, June 19: Horizontal gene transfer as a significant evolutionary driver may require an addendum to the Darwinian synthesis.
Derek E. Wildman et al., "Implications of natural selection in shaping 99.4% nonsynonymous DNA identity between humans and chimpanzees: Enlarging genus Homo" [abstract], p 7181-7188 v 100 Proc. Natl. Acad. Sci. USA, 10 Jun 2003.
Chimps are human, gene study implies, NewScientist.com, 19 May 2003.
Sean B. Carroll, "Genetics and the making of Homo sapiens" [abstract], p 849-857 v 422 Nature, 24 Apr 2003. "...A partial comparitive map indicates that there are regions of the human genome that might not be represented in chimpanzees or other apes."
K.A. Frazer et al., "Genomic DNA insertions and deletions occur frequently between humans and nonhuman primates" [text], p 341-346 v 13 n 3 Genome Res., Mar 2003.
Dario Boffeli et al., "Phylogenetic Shadowing of Primate Sequences to Find Functional Regions of the Human Genome" [abstract], p 1391-1394 v 299 Science, 28 Feb 2003.
2003, February 18: Humanoid gene arose abruptly?
Roderic Guigó et al., "Comparison of mouse and human genomes followed by experimental verification yields an estimated 1,019 additional genes" [abstract], p 1140-1145 v 100 Proc. Natl. Acad. Sci. USA, 4 Feb 2003 — "Computer programs that use patterns of evolutionary conservation... to improve the accuracy of gene prediction," ScienceDaily, 5 Feb 2003.
The Astrobiology Research Trust will undertake future funding of this Human Genome Search project, 01 Jan 2003.
2002, December 13: The Economist explains bioinformatics.
doc: Tom Ray's review of the literature pertaining to protein evolution.
Roy J. Britten, "Divergence between samples of chimpanzee and human DNA sequences is 5%, counting indels" [abstract], p 13633-13635 v 99 Proc. Natl. Acad. Sci. USA, 15 Oct 2002. Commentary: Human-chimp DNA difference trebled, NewScientist.com, 23 Sep 2002. "...Single base substitutions accounted for a difference of 1.4 per cent.... But [insertions and deletions] add around another 4.0 per cent to the genetic differences."
Hsun-Hua Chou, et al., "Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution" [abstract], p 11736-11741 v 99 Proc. Natl. Acad. Sci. USA, 3 Sep 2002. "The gene,... was mutated (knocked out) in humans in comparison with the normal, intact gene in apes," says nationalgeographic.com, 23 Aug 2002.
Wolfgang Enard et al., "Molecular evolution of FOXP2, a gene involved in speech and language" [abstract], p 869-872 v 418 Nature, 22 Aug 2002. The human and mouse versions of this gene differ by only 3 amino acids out of 717.
Joana C. Silva and Alexey S. Kondrashov, "Patterns in spontaneous mutation revealed by human–baboon sequence comparison" [abstract], p 544-547 v 18 n 11 Trends in Genetics online, 21 Aug 2002.
Study: Apes lack gene for speech, CNN.com, 15 August 2002.
Physical map of mouse genome now available, EurekAlert!, 4 August 2002.
2002, 1 August: Evolutionary advance from chimps to humans linked to viruses.
Deadly Fish Provides Clues to Human Genes, by Emily Singer, Los Angeles Times, 29 Jul 2002.
2002, July 14: Mouse vs Human
Kresimir Letinic et al., "Origin of GABAergic neurons in the human neocortex" [abstract], p 645-649 v 417 Nature. "Analysis of the human neocortex has revealed two distinct lineages of GABAergic neurons, one of which is not observed in rodents," Nature comments, 6 June 2002.
New genetic programs in Darwinism and strong panspermia, by Tom Ray and Brig Klyce — the poster presented at NASA's Astrobiology Conference, 7-11 April 2002.
How gene duplication helps in adapting to changing environments, The University of Michigan, 28 Feb 2002.
Asao Fujiyama et al., "Construction and Analysis of a Human-Chimpanzee Comparative Clone Map" [abstract], p 131-134 v 295 Science, 4 January 2002. "We detected candidate positions, including two clusters on human chromosome 21 that suggest large, nonrandom regions of difference between the two genomes."
2001, November 21: The University of Oklahoma... — our What'sNEW announcement of this webpage.