The chromosomal basis of species initiation:Prdm9as an anti-speciation gene

Abstract

Mechanisms initiating a branching process that can lead to new species are broadly classified as chromosomal and genic. Chromosomal mechanisms are supported by breeding studies involving exchanges of individual chromosomes or their segments between mouse subspecies. There are also studies of the rapidly mutating mousePR/SET-domain 9(prdm9) gene, which encodes PRDM9, a protein targeting DNA recombination hotspots. When PRDM9 is bound symmetrically with equal strength, the meiotic repair of mutations in one parental strand, based on information on the allelic strand (conversion), would seem to be unbiased in discriminating between strands. So mismatches detected between pairing paternal and maternal DNA strands (heteroduplexes) undergo unbiased conversions (to homoduplexes). This leaves uncertainty on whether a mutation has been corrected or compounded. However, it has been hypothesized that tagging of mismatch regions, so that both strands are epigenetically marked as uncertain, would make it possible over numerous generations for mutations to be corrected (biased conversions) wheneverasymmetryis detected. Thus, variation would decrease and members of a species would remain within its bounds. Intriguingly, new experimental studies show that, when chromosomally interpreted, PRDM9 also works throughasymmetricalepigenetic labelling to confine members to species bounds. To the extent that the experimentally observed and hypothetical anti-speciation asymmetries can be related, chromosomal mechanisms are further supported.