PRDM9 points the zinc finger at meiotic recombination hotspots

In most organisms, a central feature of meiosis is the induction of homologous recombination. In meiosis, homologous recombination involves searching for homologous DNA sequences on homologous chromosomes, not on sister chromatids as in somatic recombination. The result is the effective alignment of chromosome pairs (a prerequisite for their subsequent accurate segregation into separate gametes), and the reciprocal exchange of chromosomal regions between the two homologs to create new allele combinations (recombination). These rearrangements mean that each gamete contains a unique mixture of the parental alleles.In mammals, multiple lines of investigation (studies of pedigree, linkage disequilibrium and sperm typing) show that meiotic recombination events are not uniformly distributed across the genome. Instead, large areas with low median recombination rate are punctuated by discrete 1 to 2 kb regions called 'hotspots' that have a much higher recombination rate (reviewed in [1]). How this distribution arose and how it is maintained are topics of great interest to genome biologists.The punctate hotspot distribution observed in mammals is directly comparable to the detailed recombination maps also described in the budding yeast Saccharomyces cerevisiae, where the molecular steps of meiotic recombination have been characterized most clearly [1,2]. In one way this similarity is unsurprising. All organisms seem to induce meiotic recombination by the same evolutionarily conserved process: DNA double-strand break (DSB) formation catalyzed by the topoisomerase-like protein Spo11 (reviewed in [1]). Thus, all meiotic recombination hotspots are also Spo11-DSB hotspots. However, what is it about Spo11-induced recombination that causes such discrete hotspots to arise?In budding yeast, DSB hotspots generally map to short 50 to 200 bp regions of open chromatin found almost exclusively adjacent to transcription promoters, but with no obvious DNA sequence motif (reviewed in [1]). I