A Highly Polymorphic Meiotic Recombination Mouse Hotspot Exhibits Incomplete Repair

Department of Cancer Biology, Genome Plasticity Laboratory, The Scripps Research Institute, 5353 Parkside Drive RE1, Jupiter, FL 33458, USA and INSERM U674, Functional Genomics of Solid Tumors, 27 rue Juliette Dodu, 75010 Paris, France

^* To whom correspondence should be addressed. Email: pbois{at}scripps.edu.

	Abstract

The recent mapping of recombination hotspots in the human genome has demonstrated that crossover is a non-random process that occurs at well-defined positions along chromosomes. However, the mechanisms that direct hotspot turnover in complex mammalian genomes are poorly understood. Analyses in the human are impaired by the inability to genetically dissect and molecularly manipulate recombinogenic regions to test their roles in regulating hotspots. Here, using the BXD recombinant inbred strains as a crossover library, three new recombination hotspots have been identified on mouse chromosome 19. Analyses of a highly polymorphic recombination hotspot (HS22) revealed that approximately 4% of recombinant molecules display complex and incomplete repair with discontinuous conversion tracts, as well as persistent heteroduplex DNA at crossover sites in mature spermatozoa. Also, sequence analysis in the wild house mouse revealed instability at the center of this hotspot. This suggests that complete repair is not required for completion of mammalian meiosis, a scenario that leaves duplex DNA containing mismatches at crossover sites.