Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 30, Pages 12378-12383Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1109531108
Keywords
linkage disequilibrium; sperm; cross-over; conversion; meiotic drive
Categories
Funding
- Medical Research Council
- Wellcome Trust [081227/Z/06/Z]
- Boehringer Ingelheim Fonds
- Royal Society
- Louis-Jeantet Foundation
- Wellcome Trust [081227/Z/06/Z] Funding Source: Wellcome Trust
- MRC [G0601068] Funding Source: UKRI
- Medical Research Council [G0601068] Funding Source: researchfish
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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 PRDM9 regulation, 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.
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