An unexpectedly large number of human autosomal genes are subject to mono-allelic expression (MAE). In the attached report, analysis of 4,227 “MAE genes” uncovers surprisingly high genetic variation––across human populations. This increased diversity is unlikely to reflect relaxed purifying selection [See Mol Biol Evol 2o15; 32″ 820–832 for the best definition of this term].
Quite remarkably, MAE genes exhibit elevated recombination rates and an increased density of hypermutable sequence contexts. However, these factors do not fully account for the increased diversity. Authors found that elevated nucleotide diversity of MAE genes is also associated with greater allelic age: i.e. variants in these genes tend to be evoutionarily older and are enriched in polymorphisms shared by Neanderthals and chimpanzees.
Both synonymous (no change in amino-acid sequence) and non-synonymous (alteration in amino-acid sequence) alleles of MAE genes show elevated average population frequencies. Authors also observed strong enrichment of MAE signatures among genes reported to evolve under balancing selection [Meaning: Selective processes by which different alleles (variants) of a gene are actively maintained, in the gene pool of a population, at frequencies longer than that for expected from genetic drift alone; this usually happens when the heterozygote for any of these alleles possesses a higher adaptive value than the homozygote. In this way, … genetic polymorphism is conserved.] Authors propose that an important biological function of widespread MAE might be the generation of cell-to-cell heterogeneity; the increased genetic variation would then contribute to this heterogeneity.
Nat Genet Mar 2o16; 48: 231–237