title: Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios.
abstract: Even though human and chimpanzee gene sequences are nearly 99% identical, sequence comparisons can nevertheless be highly informative in identifying biologically important changes that have occurred since our ancestral lineages diverged. We analyzed alignments of 7645 chimpanzee gene sequences to their human and mouse orthologs. These three-species sequence alignments allowed us to identify genes undergoing natural selection along the human and chimp lineage by fitting models that include parameters specifying rates of synonymous and nonsynonymous nucleotide substitution. This evolutionary approach revealed an informative set of genes with significantly different patterns of substitution on the human lineage compared with the chimpanzee and mouse lineages. Partitions of genes into inferred biological classes identified accelerated evolution in several functional classes, including olfaction and nuclear transport. In addition to suggesting adaptive physiological differences between chimps and humans, human-accelerated genes are significantly more likely to underlie major known Mendelian disorders.
authors.affiliation: Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Clark
authors.forename: Stephen
authors.initials: S
authors.lastname: Glanowski
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thomas
authors.forename: Anish
authors.initials: A
authors.lastname: Kejariwal
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Todd
authors.forename: David M
authors.initials: DM
authors.lastname: Tanenbaum
authors.forename: Daniel
authors.initials: D
authors.lastname: Civello
authors.forename: Fu
authors.initials: F
authors.lastname: Lu
authors.forename: Brian
authors.initials: B
authors.lastname: Murphy
authors.forename: Steve
authors.initials: S
authors.lastname: Ferriera
authors.forename: Gary
authors.initials: G
authors.lastname: Wang
authors.forename: Xianqgun
authors.initials: X
authors.lastname: Zheng
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: White
authors.forename: John J
authors.initials: JJ
authors.lastname: Sninsky
authors.forename: Mark D
authors.initials: MD
authors.lastname: Adams
authors.forename: Michele
authors.initials: M
authors.lastname: Cargill
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000235:genetics; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005075:Biological Evolution; D019295:Computational Biology; D019143:Evolution, Molecular; D005260:Female; D005796:Genes; D030342:Genetic Diseases, Inborn / Q000235:genetics; D016678:Genome; D015894:Genome, Human; D006801:Humans; D016013:Likelihood Functions; D008297:Male; D051379:Mice / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D009154:Mutation; D002679:Pan troglodytes / Q000235:genetics*; D010802:Phylogeny; D011506:Proteins / Q000737:chemistry / Q000235:genetics; D011544:Pseudogenes; D018035:Receptors, Odorant / Q000235:genetics; D012641:Selection, Genetic; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics; D012903:Smell / Q000235:genetics; D013045:Species Specificity
chemical_list: D000596:Amino Acids; D011506:Proteins; D018035:Receptors, Odorant