The study of the biology of humans and other organisms has entered a new phase with the availability of complete genome sequences, which will make possible the development of new approaches for understanding gene function in the life cycles of organisms in both health and disease. Complete or nearly complete genome sequences are now available from human; two invertebrate animals, the fruitfly Drosophila melanogaster and the nematode worm Caenorhabditis elegans, a plant, the thale cress Arabidopsis thaliana; yeast Saccharomyces cerevisiae, and approximately 40 species of prokaryotes (bacteria and archaebacteria). An important part of deciphering the information available in complete genome sequences will involve understanding the mechanisms by which genomes evolve, including gene duplication and deletion, duplication of genomic segments or entire genomes, and horizontal transfer of genes from one genome to another. The application of bioinformatic methods to genomic sequence data is expected to play an important role in addressing these questions. The research described in this application seeks to develop computational tools that will enhance our understanding of the mechanisms of genome evolution and to apply these tools, along with standard methods of molecular evolutionary genetics, to address major currently debated questions regarding genome evolution. The following specific questions are addressed: (1) The development of a computational method of testing for past duplication of genomes or genomic segments and its application to the human genome and to other eukaryotic genomes. (2) Application of phylogenetic analysis to test the hypothesis that genes in apparently duplicated blocks in genomes duplicated simultaneously, as predicted by the hypothesis that these regions represent the remnants of ancient events of duplication of the entire genome (polyploidization events). (3) Development of a method of testing for conserved gene linkage across genomes and application of this method to the genomes of prokaryotes. (4) Application of phylogenetic analyses to test the hypothesis that horizontal gene transfers have occurred from the genomes of prokaryotes to those of eukaryotes and vice versa. (5) Examining the role of transposable elements in duplication of genomic segments by testing for nonrandom association between these elements and putatively duplicated blocks in the yeast genome.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
5R33GM066710-03
Application #
6788747
Study Section
Special Emphasis Panel (ZRG1-GNM (03))
Program Officer
Eckstrand, Irene A
Project Start
2002-08-01
Project End
2006-07-31
Budget Start
2004-08-01
Budget End
2006-07-31
Support Year
3
Fiscal Year
2004
Total Cost
$145,500
Indirect Cost
Name
University of South Carolina at Columbia
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
111310249
City
Columbia
State
SC
Country
United States
Zip Code
29208
Hughes, Austin L; Piontkivska, Helen (2005) DNA repeat arrays in chicken and human genomes and the adaptive evolution of avian genome size. BMC Evol Biol 5:12
Hughes, Austin L; Friedman, Robert (2005) Expression patterns of duplicate genes in the developing root in Arabidopsis thaliana. J Mol Evol 60:247-56
Hughes, Austin L; Ekollu, Vikram; Friedman, Robert et al. (2005) Gene family content-based phylogeny of prokaryotes: the effect of criteria for inferring homology. Syst Biol 54:268-76
Hughes, Austin L; Friedman, Robert (2004) Recent mammalian gene duplications: robust search for functionally divergent gene pairs. J Mol Evol 59:114-20
Piontkivska, Helen; Zhang, Yi; Green, Eric D et al. (2004) Multi-species sequence comparison reveals dynamic evolution of the elastin gene that has involved purifying selection and lineage-specific insertions/deletions. BMC Genomics 5:31
Friedman, Robert; Hughes, Austin L (2004) Two patterns of genome organization in mammals: the chromosomal distribution of duplicate genes in human and mouse. Mol Biol Evol 21:1008-13
Hughes, Austin L; Friedman, Robert (2004) Pattern of divergence of amino acid sequences encoded by paralogous genes in human and pufferfish. Mol Phylogenet Evol 32:337-43
Friedman, Robert; Drake, John W; Hughes, Austin L (2004) Genome-wide patterns of nucleotide substitution reveal stringent functional constraints on the protein sequences of thermophiles. Genetics 167:1507-12
Hughes, Austin L; Friedman, Robert (2004) Differential loss of ancestral gene families as a source of genomic divergence in animals. Proc Biol Sci 271 Suppl 3:S107-9
Hughes, Austin L; Friedman, Robert (2004) Transposable element distribution in the yeast genome reflects a role in repeated genomic rearrangement events on an evolutionary time scale. Genetica 121:181-5

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