Impact of the Presence of Paralogs on Sequence Divergence in a Set of Mouse-Human Orthologs

Using a large set of orthologous human and mouse gene pairs, we have characterized genes that have been retained in duplicate in human over timescales comparable to the time of speciation of human and mouse. Orthologous gene pairs for which a paralogous gene has been present for much or all of the time since speciation show an increased rate of nonsynonymous substitution. We have related rate of divergence to functional classification using the Gene Ontology terms. Protein function was found, in some cases, to have a larger impact on rate of evolution than the presence or absence of a paralog. No evidence was found that genes that have been retained in duplicate are weighted toward any functional categories. An increase in the ratio of nonsynonymous to synonymous changes following duplication has previously been reported. However, because amino acid sequences include conservative as well as more freely evolving sites, the ratio of nonsynonymous to synonymous changes tends to be higher for closely related pairs. By measuring the divergence of orthologs only and comparing between genes for which a paralogous gene is either present or absent, we have compared gene pairs that share a common divergence time. We have also found that shorter genes have a higher probability of being found duplicated in the human genome, possibly reflecting a mutational effect.