Elevated Mutagenicity in Meiosis and Its Mechanism

Diploid germ cells produce haploid gametes through meiosis, a unique type of cell division. Independent reassortment of parental chromosomes and their recombination leads to ample genetic variability among the gametes. Importantly, new mutations also occur during meiosis, at frequencies much higher than during the mitotic cell cycles. These meiotic mutations are associated with genetic recombination and depend on double-strand breaks (DSBs) that initiate crossing over. Indeed, sequence variation among related strains is greater around recombination hotspots than elsewhere in the genome, presumably resulting from recombination-associated mutations. Significantly, enhanced mutagenicity in meiosis may lead to faster divergence during evolution, as germ-line mutations are the ones that are transmitted to the progeny and thus have an evolutionary impact. The molecular basis for mutagenicity in meiosis may be related to the repair of meiotic DSBs by polymerases, or to the exposure of single-strand DNA to mutagenic agents during its repair.