Prdm9 controls activation of mammalian recombination hotspots

Abstract

Mammalian meiotic recombination, which preferentially occurs at specialized sites called hotspots, ensures the orderly segregation of meiotic chromosomes and creates genetic variation among offspring. A locus on mouse chromosome 17, which controls activation of recombination at multiple distant hotspots, has been mapped within a 181-kilobase interval, three of whose genes can be eliminated as candidates. The remaining gene, Prdm9, codes for a zinc finger containing histone H3K4 trimethylase that is expressed in early meiosis and whose deficiency results in sterility in both sexes. Mus musculus exhibits five alleles of Prdm9; human populations exhibit two predominant alleles and multiple minor alleles. The identification of Prdm9 as a protein regulating mammalian recombination hotspots initiates molecular studies of this important biological control system.

Fig. 1

Fine mapping the location of Rcr1. Upper line shows the position, in Mb (Ensembl Build 37), of the markers used for genetic mapping. Crossovers collected in this region are marked with blue for B6 DNA and red for CAST. On the left are the serial numbers of the male progeny tested for recombination activity. The critical region containing Rcr1 is between markers at 15.589 and 15.770 Mb. Below are the order and coordinates of the four protein-coding genes in the critical region.