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.
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