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Diversity of Prdm9 Zinc Finger Array in Wild Mice Unravels New Facets of the Evolutionary Turnover of this Coding Minisatellite

Authors: Buard, Jérôme; Rivals, Eric; Dunoyer de Segonzac, Denis; Garres, Charlotte; Caminade, Pierre; de Massy, Bernard; Boursot, Pierre;

Diversity of Prdm9 Zinc Finger Array in Wild Mice Unravels New Facets of the Evolutionary Turnover of this Coding Minisatellite

Abstract

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.

Keywords

Heterozygote, Bioinformatics, Science, Gene Dosage, 612, Animal phylogenetics, [SDV.GEN] Life Sciences [q-bio]/Genetics, Minisatellite Repeats, Evolution, Molecular, Mice, Open Reading Frames, Sequence alignment, Species Specificity, Animals, Mammalian genomics, Amino Acids, Nucleotide Motifs, Alleles, Phylogeny, [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM], [SDV.GEN]Life Sciences [q-bio]/Genetics, Phylogenetic analysis, Binding Sites, Genome, Geography, Q, R, Genetic Variation, Repeated sequences, Zinc Fingers, Histone-Lysine N-Methyltransferase, Sequence Analysis, DNA, Genome evolution, Protein Structure, Tertiary, Mammalian genomics;Phylogeography;Repeated sequences;Sequence alignment;Alleles;Genome evolution;Animal phylogenetics;Phylogenetic analysis, Phylogeography, Bio-informatique, Medicine, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Research Article

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
61
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Top 10%
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