Diversity of Prdm9 zinc finger array in wild mice unravels new facets of the evolutionary turnover of this coding minisatellite

PLoS One. 2014 Jan 13;9(1):e85021. doi: 10.1371/journal.pone.0085021. eCollection 2014.


In humans and mice, meiotic recombination events cluster into narrow hotspots whose genomic positions are defined by the PRDM9 protein via its DNA binding domain constituted of an array of zinc fingers (ZnFs). High polymorphism and rapid divergence of the Prdm9 gene ZnF domain appear to involve positive selection at DNA-recognition amino-acid positions, but the nature of the underlying evolutionary pressures remains a puzzle. Here we explore the variability of the Prdm9 ZnF array in wild mice, and uncovered a high allelic diversity of both ZnF copy number and identity with the caracterization of 113 alleles. We analyze features of the diversity of ZnF identity which is mostly due to non-synonymous changes at codons -1, 3 and 6 of each ZnF, corresponding to amino-acids involved in DNA binding. Using methods adapted to the minisatellite structure of the ZnF array, we infer a phylogenetic tree of these alleles. We find the sister species Mus spicilegus and M. macedonicus as well as the three house mouse (Mus musculus) subspecies to be polyphyletic. However some sublineages have expanded independently in Mus musculus musculus and M. m. domesticus, the latter further showing phylogeographic substructure. Compared to random genomic regions and non-coding minisatellites, none of these patterns appears exceptional. In silico prediction of DNA binding sites for each allele, overlap of their alignments to the genome and relative coverage of the different families of interspersed repeated elements suggest a large diversity between PRDM9 variants with a potential for highly divergent distributions of recombination events in the genome with little correlation to evolutionary distance. By compiling PRDM9 ZnF protein sequences in Primates, Muridae and Equids, we find different diversity patterns among the three amino-acids most critical for the DNA-recognition function, suggesting different diversification timescales.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acids / genetics
  • Animals
  • Binding Sites
  • Evolution, Molecular*
  • Gene Dosage
  • Genetic Variation*
  • Genome / genetics
  • Geography
  • Heterozygote
  • Histone-Lysine N-Methyltransferase / chemistry
  • Histone-Lysine N-Methyltransferase / genetics*
  • Mice
  • Minisatellite Repeats / genetics*
  • Nucleotide Motifs / genetics
  • Open Reading Frames / genetics*
  • Phylogeny
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA
  • Species Specificity
  • Zinc Fingers / genetics*


  • Amino Acids
  • Histone-Lysine N-Methyltransferase

Grant support

JB and BdM are supported by the Centre National de la Recherche Scientifique, the Agence Nationale de la Recherche (09-BLAN-0269-01), and the Fondation pour la Recherche Médicale. DD is recipient of a fellowship by from the Labex « EpigenMed » program of MENRT. The project was partly funded by the Conseil Scientifique of Université Montpellier 2 (AAP2011 to PB). ER is supported by the Region Languedoc Roussillon (grant Chercheur d'Avenir), the NUMEV Labex, the MASTODONS Défi from CNRS, and by Investissements d'Avenir (grant Institut Computational Biology). The funders has no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.