Inferring nonneutral evolution from human-chimp-mouse orthologous gene trios |
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Authors: | Clark Andrew G Glanowski Stephen Nielsen Rasmus Thomas Paul D Kejariwal Anish Todd Melissa A Tanenbaum David M Civello Daniel Lu Fu Murphy Brian Ferriera Steve Wang Gary Zheng Xianqgun White Thomas J Sninsky John J Adams Mark D Cargill Michele |
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Affiliation: | Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA. |
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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. |
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