Positive Selection in the Human Genome Inferred from Human–Chimp–Mouse Orthologous Gene Alignments
- A.G. CLARK,
- S. GLANOWSKI,
- R. NIELSEN,
- P. THOMAS,
- A. KEJARIWAL,
- M.J. TODD,
- D.M. TANENBAUM,
- D. CIVELLO,
- F. LU,
- B. MURPHY,
- S. FERRIERA,
- G. WANG,
- X. ZHENG,
- T.J. WHITE,
- J.J. SNINSKY,
- M.D. ADAMS, and
- M. CARGILL
- *Molecular Biology & Genetics, Cornell University, Ithaca, New York 14853; †Applied Biosystems, Rockville, Maryland 20850; ‡Biological Statistics & Computational Biology, Cornell University, Ithaca, New York 14853; ¶Protein Informatics, Celera Genomics, Foster City, California 94404; §Celera Genomics, Rockville, Maryland 20850; **Celera Diagnostics, Alameda, California 94502.
This extract was created in the absence of an abstract.
Excerpt
The availability of genomic sequence from diverse organisms allows the opportunity to identify genes thathave undergone evolutionary divergence from our mostrecent common ancestors. By fitting aligned DNA sequences from multiple species to models of sequence divergence it is possible to distinguish divergence due torandom drift from that caused by nonneutral processessuch as natural selection. The key to this problem is to realize that nucleotide sites can be partitioned a priori according to whether substitutions at these sites change theencoded amino acid or are silent. Under neutrality, thesetwo types of substitutions are expected to be distributed atrandom, and a variety of tests have been devised to testthis null hypothesis. The identification of genes that haveundergone positive Darwinian evolution (inferred froman excess of amino acid-changing substitutions) mightlead to hypotheses of physiological mechanisms that underlie the specialization of species and their reproductiveisolation. Furthermore, discovery of genes that appear toshow adaptive evolution in humans may lead to the identification of genes important in human disease...
