PRDM9 variants and recombination in Euro vs African populations

[warwick]

Proc Natl Acad Sci U S A. 2011 Jul 12. [Epub ahead of print]
Variants of the protein PRDM9 differentially regulate a set of human meiotic recombination hotspots highly active in African populations.
Berg IL, Neumann R, Sarbajna S, Odenthal-Hesse L, Butler NJ, Jeffreys AJ.
Source

Department of Genetics, University of Leicester, Leicester LE1 7RH, United Kingdom.
Abstract
PRDM9 is a major specifier of human meiotic recombination hotspots, probably via binding of its zinc-finger repeat array to a DNA sequence motif associated with hotspots. However, our view of PRDM9regulation, in terms of motifs defined and hotspots studied, has a strong bias toward the PRDM9 A variant particularly common in Europeans. We show that population diversity can reveal a second class of hotspots specifically activated by PRDM9 variants common in Africans but rare in Europeans. These African-enhanced hotspots nevertheless share very similar properties with their counterparts activated by the A variant. The specificity of hotspot activation is such that individuals with differing PRDM9 genotypes, even within the same population, can use substantially if not completely different sets of hotspots. Each African-enhanced hotspot is activated by a distinct spectrum of PRDM9 variants, despite the fact that all are predicted to bind the same sequence motif. This differential activation points to complex interactions between the zinc-finger array and hotspots and identifies features of the array that might be important in controlling hotspot activity.