Variants of the Protein PRDM9 Differentially Regulate a Set of Human Meiotic Recombination Hotspots Highly Active in African Populations

Proc Natl Acad Sci U S A. 2011 Jul 26;108(30):12378-83. doi: 10.1073/pnas.1109531108. Epub 2011 Jul 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Continental Ancestry Group / genetics*
  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Crossing Over, Genetic
  • DNA / genetics
  • European Continental Ancestry Group / genetics
  • Gene Conversion
  • Gene Frequency
  • Genetic Variation*
  • Histone-Lysine N-Methyltransferase / genetics*
  • Histone-Lysine N-Methyltransferase / metabolism
  • Humans
  • Linkage Disequilibrium
  • Male
  • Meiosis / genetics
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • Recombination, Genetic
  • Spermatozoa / metabolism


  • DNA
  • Histone-Lysine N-Methyltransferase
  • PRDM9 protein, human