Trans-Regulation of Mouse Meiotic Recombination Hotspots by Rcr1

Abstract

Meiotic recombination is required for the orderly segregation of chromosomes during meiosis and for providing genetic diversity among offspring. Among mammals, as well as yeast and higher plants, recombination preferentially occurs at highly delimited chromosomal sites 1–2 kb long known as hotspots. Although considerable progress has been made in understanding the roles various proteins play in carrying out the molecular events of the recombination process, relatively little is understood about the factors controlling the location and relative activity of mammalian recombination hotspots. To search for trans-acting factors controlling the positioning of recombination events, we compared the locations of crossovers arising in an 8-Mb segment of a 100-Mb region of mouse Chromosome 1 (Chr 1) when the longer region was heterozygous C57BL/6J (B6) × CAST/EiJ (CAST) and the remainder of the genome was either similarly heterozygous or entirely homozygous B6. The lack of CAST alleles in the remainder of the genome resulted in profound changes in hotspot activity in both females and males. Recombination activity was lost at several hotspots; new, previously undetected hotspots appeared; and still other hotspots remained unaffected, indicating the presence of distant trans-acting gene(s) whose CAST allele(s) activate or suppress the activity of specific hotspots. Testing the activity of three activated hotspots in sperm samples from individual male progeny of two genetic crosses, we identified a single trans-acting regulator of hotspot activity, designated Rcr1, that is located in a 5.30-Mb interval (11.74–17.04 Mb) on Chr 17. Using an Escherichia coli cloning assay to characterize the molecular products of recombination at two of these hotspots, we found that Rcr1 controls the appearance of both crossover and noncrossover gene conversion events, indicating that it likely controls the sites of the double-strand DNA breaks that initiate the recombination process.

Death ofPRDM9coincides with stabilization of the recombination landscape in the dog genome

“…Hotspot locations are typically not consistent between humans and chimpanzees (Ptak et al 2005;Winckler et al 2005), and there is evidence of population-specific hotspots in humans (Graffelman et al 2007;Berg et al 2010;Kong et al 2010). Hotspot locations have also been shown to vary among different mouse strains (Gray et al 2009;Parvanov et al 2009;Baudat et al 2010). These results indicate that there is a rapid turnover of hotspot locations in mammals.…”

Fine-Scale Maps of Recombination Rates and Hotspots in the Mouse Genome

“…The dense map of single nucleotide polymorphisms (SNPs) created by the HapMap Project enabled the highresolution mapping of recombination rates in the human genome and led to the identification of 33,000 recombination hotspots with a coalescent method . The very large number of hotspots and the very high resolution of this mapping made it possible to pinpoint sequence motifs in these hotspots, one of which was instrumental in finding a gene, PRDM9, thought to be a critical component of the recombination mechanism (Baudat and de Massy 2007;Grey et al 2009;Parvanov et al 2009). …”

Evolution of the Genomic Recombination Rate in Murid Rodents

“…Much of this variation is thought to derive from differences in the density and intensity of recombination hotspots (Coop et al 2008;Webb et al 2008;Paigen and Petkov 2010), short genomic regions with very high rates of crossing over. Recombination rates on this fine scale evolve rapidly (Ptak et al 2005;Winckler et al 2005;Jeffreys and Neumann 2009), and loci that confer differences in hotspot activity within and between species have been identified ( Jeffreys and Neumann 2005;Baudat and de Massy 2007;Parvanov et al 2009Parvanov et al , 2010Baudat et al 2010).…”