Genomic Regionality in Rates of Evolution Is Not Explained by Clustering of Genes of Comparable Expression Profile

In mammalian genomes, linked genes show similar rates of evolution, both at fourfold degenerate synonymous sites (K4) and at nonsynonymous sites (KA). Although it has been suggested that the local similarity in the synonymous substitution rate is an artifact caused by the inclusion of disparately evolving gene pairs, we demonstrate here that this is not the case: after removal of disparately evolving genes, both (1) linked genes and (2) introns from the same gene have more similar silent substitution rates than expected by chance. What causes the local similarity in both synonymous and nonsynonymous substitution rates? One class of hypotheses argues that both may be related to the observed clustering of genes of comparable expression profile. We investigate these hypotheses using substitution rates from both human-mouse and mouse-rat comparisons, and employing three different methods to assay expression parameters. Although we confirm a negative correlation of expression breadth with both K4 and KA, we find no evidence that clustering of similarly expressed genes explains the clustering of genes of comparable substitution rates. If gene expression is not responsible, what about other causes? At least in the human-mouse comparison, the local similarity in KA can be explained by the covariation of KA and K4. As regards K4, our results appear consistent with the notion that local similarity is due to processes associated with meiotic recombination.