Chromosome-wide distribution and characterization of intersubspecific meiotic noncrossovers in mice

Abstract

11During meiosis, the recombination-initiating DNA double-strand breaks (DSBs) are repaired 12 by crossovers or noncrossovers (gene conversions). While crossovers are easily detectable, 13 the noncrossover identification is hampered by the small size of their converted tracts and 14 the necessity of sequence polymorphism to detect them. We report identification and 15 characterization of a mouse chromosome-wide set of noncrossovers by NGS sequencing of 16 10 mouse chromosome substitution strains. Based on 94 identified noncrossovers we 17 determined the mean length of a conversion tract to be 32 basepairs. The spatial 18 chromosome-wide distribution of noncrossovers and crossovers significantly differed, 19 though both sets overlapped the known hotspots of PRDM9-directed histone methylation 20 and DNA DSBs, thus proving their origin in the standard DSB repair pathway. A significant 21 deficit of noncrossovers descending from asymmetric DSBs pointed to sister chromatids as 22 an alternative template for their repair. The finding has implications for the molecular 23 mechanism of hybrid sterility in mice. 24