To establish 1:1 orthology, each human gene and putative nonhuman ortholog was examined for evidence of an inparalog (a Figure S3 .) When v#1, these fractions are estimates of the false positive rate. Each data point is based on 1000 data sets simulated with evolver [84] under the assumption of a constant v among lineages and among sites (model M0). All other parameters (including the transition-transversion ratio k, the codon frequencies, and the branch lengths) were fixed at values estimated from the real data. Results are shown for short (200-codon) and long (500-codon) genes and three sets of species: hominids (human and chimpanzee), primates (human, chimpanzee, and macaque), and all six mammals. Details on the computation of P-values are given in Text S1. Note the logarithmic scale on the x-axis. doi:10.1371/journal.pgen.1000144.g006 paralog arising from a recent duplication [82] ) with respect to the other species. Specifically, if either gene had a BLASTN match within the same species (with $80% CDS alignment) that was more similar than the two orthologs were to each other, then that gene was considered recently duplicated and was excluded from the analyses of positive selection. The removal of a duplicated gene did not require an ortholog set to be discarded entirely, provided a human gene and $2 nonhuman orthologs still remained. A collection of genes and gene predictions from the UCSC Genome Browser were used in the identification of inparalogs. When comparing rodent vs. non-rodent and rodent vs. rodent distances, a simple correction for unequal rates of evolution was applied. Further details are given in Text S1.