PMID- 24454780 OWN - NLM STAT- MEDLINE DCOM- 20140918 LR - 20240320 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 1 DP - 2014 TI - Diversity of Prdm9 zinc finger array in wild mice unravels new facets of the evolutionary turnover of this coding minisatellite. PG - e85021 LID - 10.1371/journal.pone.0085021 [doi] LID - e85021 AB - 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. FAU - Buard, Jerome AU - Buard J AD - Institute of Human Genetics, UPR 1142, Centre National de la Recherche Scientifique, Montpellier, France. FAU - Rivals, Eric AU - Rivals E AD - Laboratoire d'Informatique, de Robotique et de Microelectronique de Montpellier, UMR 5506, Universite Montpellier 2, Centre National de la Recherche Scientifique, Montpellier, France ; Institut de Biologie Computationnelle, Montpellier, France. FAU - Dunoyer de Segonzac, Denis AU - Dunoyer de Segonzac D AD - Institute of Human Genetics, UPR 1142, Centre National de la Recherche Scientifique, Montpellier, France ; Institut des Sciences de l'Evolution Montpellier, Universite Montpellier 2, Centre National de la Recherche Scientifique, Institut de Recherche pour le Developpement, Montpellier, France. FAU - Garres, Charlotte AU - Garres C AD - Institute of Human Genetics, UPR 1142, Centre National de la Recherche Scientifique, Montpellier, France ; Institut des Sciences de l'Evolution Montpellier, Universite Montpellier 2, Centre National de la Recherche Scientifique, Institut de Recherche pour le Developpement, Montpellier, France. FAU - Caminade, Pierre AU - Caminade P AD - Institut des Sciences de l'Evolution Montpellier, Universite Montpellier 2, Centre National de la Recherche Scientifique, Institut de Recherche pour le Developpement, Montpellier, France. FAU - de Massy, Bernard AU - de Massy B AD - Institute of Human Genetics, UPR 1142, Centre National de la Recherche Scientifique, Montpellier, France. FAU - Boursot, Pierre AU - Boursot P AD - Institut des Sciences de l'Evolution Montpellier, Universite Montpellier 2, Centre National de la Recherche Scientifique, Institut de Recherche pour le Developpement, Montpellier, France. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140113 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Amino Acids) RN - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase) SB - IM MH - Alleles MH - Amino Acids/genetics MH - Animals MH - Binding Sites MH - *Evolution, Molecular MH - Gene Dosage MH - *Genetic Variation MH - Genome/genetics MH - Geography MH - Heterozygote MH - Histone-Lysine N-Methyltransferase/chemistry/*genetics MH - Mice MH - Minisatellite Repeats/*genetics MH - Nucleotide Motifs/genetics MH - Open Reading Frames/*genetics MH - Phylogeny MH - Protein Structure, Tertiary MH - Sequence Analysis, DNA MH - Species Specificity MH - Zinc Fingers/*genetics PMC - PMC3890296 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2014/01/24 06:00 MHDA- 2014/09/19 06:00 PMCR- 2014/01/13 CRDT- 2014/01/24 06:00 PHST- 2013/10/26 00:00 [received] PHST- 2013/11/20 00:00 [accepted] PHST- 2014/01/24 06:00 [entrez] PHST- 2014/01/24 06:00 [pubmed] PHST- 2014/09/19 06:00 [medline] PHST- 2014/01/13 00:00 [pmc-release] AID - PONE-D-13-43883 [pii] AID - 10.1371/journal.pone.0085021 [doi] PST - epublish SO - PLoS One. 2014 Jan 13;9(1):e85021. doi: 10.1371/journal.pone.0085021. eCollection 2014.