Genes with monoallelic expression contribute disproportionately to genetic diversity in humans.

Abstract

An unexpectedly large number of human autosomal genes are subject to monoallelic expression (MAE). Our analysis of 4,227 such genes reveals surprisingly high genetic variation across human populations. This increased diversity is unlikely to reflect relaxed purifying selection. Remarkably, MAE genes exhibit elevated recombination rate and increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. We find that the elevated nucleotide diversity of MAE genes is also associated with greater allelic age: their variants tend to be older and are enriched in polymorphisms shared with Neanderthals and chimpanzees. Both synonymous and nonsynonymous alleles in MAE genes have elevated average population frequencies. We also observed strong enrichment of the MAE signature among genes reported to evolve under balancing selection. We propose that an important biological function of widespread MAE might be generation of cell-to-cell heterogeneity; the increased genetic variation contributes to this heterogeneity.