Duplication Mechanism and Disruptions in Flanking Regions Determine the Fate of Mammalian Gene Duplicates

Abstract

Here we identify duplicated genes in five mammalian genomes and classify these duplicates based on the mechanisms by which they were generated. Retrotransposition accounts for at least half of all predicted duplicate genes in these genomes, with tandem and interspersed DNA-mediated duplicates comprising the other half. Estimation of the evolutionary rates in each class revealed greater rate asymmetry between retrotransposed and interspersed DNA duplicate pairs than between tandem duplicates, suggesting that retrotransposed and interspersed DNA duplicates are diverging more quickly. In an attempt to understand the basis of this asymmetry, we identified disruption of flanking DNA as an indicator of new duplicate fate-loss of local synteny accelerates the asymmetry of divergence of interspersed DNA duplicates. We also show that intact retrogenes are enriched in intergenic regions and indel purified regions of the human genome. Moreover, intact retrogenes closest to annotated genes show the greatest levels of purifying selective pressure. Together, these findings suggest that the differential evolution of duplicate genes may be significantly influenced by changes in local genome architecture.