Nature Genetics Advance Online Publication Arabidopsis Meiotic Crossover Hot Spots Overlap with H2a.z Nucleosomes at Gene Promoters

In fungi and mammals, the majority of meiotic recombination occurs in narrow (1–2 kb) hot spots 1–3. Human and mouse hot spots are targeted to DNA sequence motifs by the zinc finger domain protein PRDM9 (refs. 4–11). PRDM9-dependent crossovers occur mainly in intergenic regions and introns, with the lowest amount of recombination occurring in exons 9,12. PRDM9 also contains a SET domain with histone H3 Lys4 tri-methyltransferase activity and targets this modification to hot spot chro-matin during meiosis 11,13–15. In contrast, hot spots in the budding yeast Saccharomyces cerevisiae are not sequence dependent, show polarity within genes and occur predominantly at regions of LND in gene promoters 3,16–21. However, S. cerevisiae hot spots are also closely associated with H3K4me3, which is required for wild-type patterns of recombination 22–26. Therefore, mammalian and yeast recombination hot spots are specified to varying degrees by genetic and epigenetic information. Although recom-bination rates vary extensively within plant genomes 27–33 , the control of meiotic crossover hot spots in plants is poorly understood. We therefore sought to map fine-scale recombination rates in A. thaliana, which lacks PRDM9, and investigate the contribution of DNA sequence and chromatin to the control of plant hot spot locations. RESULTS Coalescent analysis of Arabidopsis genetic variation To generate a map of crossover frequency and hot spots in A. thaliana, we applied coalescent theory to a large SNP data set generated from 80 Eurasian accessions 34. We used the Interval program from the LDhat package to estimate the population-scaled recombination rate between pairs of SNPs 2. After conditioning on diallelic SNPs in unique sequence, we analyzed a total of 2,112,845 SNPs (17.7 SNPs per kb) (Supplementary Table 1). We validated the crossover frequencies estimated by Interval by comparing them to a consensus genetic map from 17 F 2 populations 33 , which had been generated previously using the MergeMap program 35. We observed correlations between the historical and experimental crossover frequencies for all chromosomes (e.g., correlations of 0.44–0.55 at the 500-kb scale), although there were regions of substantial divergence (Fig. 1a, Supplementary Fig. 1 and Supplementary Tables 2 and 3). Structural genetic variation between accessions may contribute to differences in recombination rate measurements. For example, megabase inversions on chromosome 3 between the Col and Sha accessions 33,36 , and on the short arm of chromosome 4 between the Col and Ler accessions 37 , cause crossover suppression. Population genetic forces, such as …

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