A Holistic View of Evolutionary Rates in Paralogous and Orthologous Genes

Abstract

Much work has been done on the evolutionary divergence of duplicated genes in protein coding regions. However, this remains a partial view, and little is known how duplicated genes diverge in non-coding regions, which can play an important role in the evolutionary preservation of duplicated genes. Here we compared the evolutionary rates of different parts of of duplicated genes in the human and mouse genomes, including 5’-UTRs, coding regions, 3’-UTRs, and 500 bps upstream and downstram of the untranslated regions. Results show that compared to orthologous genes, the ratios of the genetic distance of noncoding regions such as UTRs and upstream and downstream regions vs. synonymous substitutions tend to be smaller in paralogous genes, suggesting that synonymous substitutions benefit more greatly from relaxed selective constraints than noncoding regions. Moreover, we also examined the most frequent types of rate comparison among different genic regions in both orthologs and paralogs and found that the ranks of the most frequent types of rate comparison differ little between human paralogs and mouse paralogs, but differ greatly from those in orthologs, suggesting that duplication enables changes of evolutionary dynamics along different parts of genes. We also classified duplicated genes into three categories based on their chromosomal locations, tandem duplicates, intra-chromosomal duplicates, and inter-chromosomal duplicates. Results show that in both the human and mouse, selective constraint (measured by K _a /K _s ) on intra-chromosomal duplicates tends to be much lower than that on tandem duplicates, which in turn is significantly lower than that on inter-chromosomal duplicates. This shows that genomic location is an important factor in determining the evolutionary divergence of duplicated genes.