DNA cytosine methylation suppresses meiotic recombination at the sex-determining region

Meiotic recombination between homologous chromosomes is vital to maximize genetic variation among offspring during sexual reproduction. However, sex-determining regions (SDRs) and mating-type regions (MTRs) of chromosomes are often rearranged with respect to each other and blocked for recombination to preserve linkage of genes or alleles adapted for sexually dimorphic roles. However, it remains unclear whether structural rearrangements between MTR or SDR haplotypes are the consequence or cause of blocked recombination, and what other mechanisms might contribute to inhibition of recombination. Here, we describe an epigenetic mechanism that limits meiotic recombination at the mating-type locus (MT) in the green alga Chlamydomonas reinhardtii which has two structurally rearranged haplotypes, MT+ and MT-. We identify a maintenance DNA methyltransferase, DNMT1, whose loss causes a 95% reduction of 5-methylcytosines (5mCs) in the nuclear genome. While the 5mC deficiency causes no discernible alteration in haploid vegetative growth or sexual differentiation, dnmt1 homozygotes have a substantial reduction in meiotic spore viability. Strikingly, in dnmt1 homozygotes, anomalous meiotic recombination takes place at MT, generating haploid progenies containing both plus and minus markers due to crossovers within MT. Although the repressive histone methylation mark H3K9me1 at MT is lost concurrently with DNA methylation in dnmt1 strains, loss of histone methylation alone caused by mutation of the histone methyltransferase gene encoding SET3p does not lead to anomalous recombination at MT. These findings suggest that rearrangements between MTR or SDR haplotypes are insufficient to block recombination and identify a new role for DNA methylation as a meiotic recombination inhibitory modification in chromatin.