A universally observed feature of meiotic recombination is a highly non-uniform distribution of meiotic crossovers across the genome. Although it has become evident that hotspots of recombination are relatively unstable in evolution, the magnitude of the variation of recombination profiles on a genome-wide scale is unknown. To study the underlying mechanisms responsible for the birth, life and death of recombination hotspots we decided to estimate the genome-wide variation in profiles of recombination. This has become possible due to the recent confluence of two major developments: improvements in the computational approaches to calculate genome-wide recombination profiles from linkage disequilibrium data and the availability of a very dense catalog of genetic markers (single nucleotide polymorphisms, SNPs) in human beings (phase I of the HapMap, 106 SNPs). We found that a large fraction of hotspots of recombination varies between the four populations sampled by the HapMap project. Next, we showed that many (25%) present-day crossovers in one population are located in regions without historical hotspots. We conclude that profiles of human meiotic recombination are quickly changing over time. This absence-or-presence polymorphism of recombination hotspots is unlikely due to local DNA sequence variation but most likely reflects DNA sequence changes in distant elements or epigenetic factors. We are in the process of mapping the variability of the hotspots (epigenetic map) and/or the genetic determinants in trans responsible for this variability by generating a higher resolution recombination hotspot map from the phase II HapMap (5X106 SNPs) and from the ENCODE regions.
