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.
Highlights
In sexually reproducing species, novel combinations of alleles are created at each generation by the process of meiotic recombination
Variation of the number of Zinc finger repeats We amplified by PCR the zinc fingers (ZnFs) domain of Prdm9 (Fig. 1A) using primers that flank this region, which consists of tandemly repeated units of 84 nucleotides, each representing a ZnF
We have attempted to reconstruct the evolutionary history of the Prdm9 ZnF arrays sequenced, which is challenging given its minisatellite structure
Summary
Novel combinations of alleles are created at each generation by the process of meiotic recombination. This process of exchange between paternal and maternal chromosomes, called homologs, takes place during the prophase of the first meiotic division. COs create connections between homologs that are important for the proper segregation of chromosomes at the first meiotic division, and the absence of recombination often leads to sterility [1]. A few sexually reproducing species show the absence of meiotic recombination in one sex, indicating that alternative mechanisms for ensuring a proper reductional segregation and not involving COs, are possible [2]. Understanding the controls of meiotic recombination both in frequencies and distribution in the genome is a major goal for the understanding of how this process ensures a proper chromosome segregation and how it shapes genome diversity [7]
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