Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios.
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.
Clark
Andrew G
AG
Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA.
Glanowski
Stephen
S
Nielsen
Rasmus
R
Thomas
Paul D
PD
Kejariwal
Anish
A
Todd
Melissa A
MA
Tanenbaum
David M
DM
Civello
Daniel
D
Lu
Fu
F
Murphy
Brian
B
Ferriera
Steve
S
Wang
Gary
G
Zheng
Xianqgun
X
White
Thomas J
TJ
Sninsky
John J
JJ
Adams
Mark D
MD
Cargill
Michele
M
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
D000596:Amino Acids; D011506:Proteins; D018035:Receptors, Odorant