Similarity of synonymous substitution rates across mammalian genomes

Given that a gene has a high (or low) synonymous substitution rate in one mammalian species, will it also have a high (or low) synonymous substitution rate in another mammalian species? Such similarities in the rate of synonymous substitution can reveal both selective pressures and neutral processes acting on mammalian gene sequences; however, the existence of such an effect has been a matter of disagreement. We resolve whether such synonymous substitution rate similarities exist using 7462 ortholog triplets aligned across rat, mouse, and human, a dataset two orders of magnitude larger than previous studies. We find that a gene’s synonymous substitution rate in the rat-mouse branch of the phylogeny is correlated with its rate in the branch connecting human and the rat-mouse ancestor. We confirm this for several different measures of synonymous substitution rate, including corrections for base composition and CpG dinucleotides, and we verify the results in the larger mouse-human-rat-dog phylogeny. This similarity of rates is most apparent for genes in which synonymous sites are well conserved across species, suggesting that a significant component of the effect is due to purifying selection. We observe rate correlations at a resolution as fine as a few hundred kilobases, and the genes with the most similar synonymous substitution rates are enriched for regulatory functions. Genes with above-average substitution rates also exhibit significant, though somewhat weaker, rate correlations, suggesting that some neutral processes may have persisted in the phylogeny as well.