Fine-scale variation in meiotic recombination in Mimulus inferred from population shotgun sequencing

Abstract

Meiotic recombination rates can vary widely across genomes, with hotspots of intense activity interspersed among cold regions. In yeast, hotspots tend to occur in promoter regions of genes, whereas in humans and mice, hotspots are largely defined by binding sites of the positive-regulatory domain zinc finger protein 9. To investigate the detailed recombination pattern in a flowering plant, we use shotgun resequencing of a wild population of the monkeyflower Mimulus guttatus to precisely locate over 400,000 boundaries of historic crossovers or gene conversion tracts. Their distribution defines some 13,000 hotspots of varying strengths, interspersed with cold regions of undetectably low recombination. Average recombination rates peak near starts of genes and fall off sharply, exhibiting polarity. Within genes, recombination tracts are more likely to terminate in exons than in introns. The general pattern is similar to that observed in yeast, as well as in positiveregulatory domain zinc finger protein 9-knockout mice, suggesting that recombination initiation described here in Mimulus may reflect ancient and conserved eukaryotic mechanisms.plant biology | population genetics M eiotic recombination is a highly regulated process that enables pairing of homologous chromosomes and, by the formation of crossovers, ensures proper segregation (1). Along with mutation, drift, and selection, recombination is a critical factor in shaping genome-wide sequence variation. Recombination rates vary substantially across eukaryote genomes (2) in a manner that we are only beginning to understand. In humans and mice, the location of regions of strong recombination ("hotspots") is largely determined by positive-regulatory domain zinc finger protein 9 (PRDM9) binding sites (3), whereas in yeast such regions are associated with nucleosome-depleted open chromatin often associated with gene promoters (4). When PRDM9 is disabled in mice, hotspots tend to relocalize to promoter regions (5). In flowering plants, at least one example of a promoter-associated hotspot has been reported (6), but it remains an open question whether this is a general tendency in plants.The positions of crossovers and the boundaries of gene conversion tracts resulting from meiotic recombination are often imprecisely known, because they can only be identified based on the location of nearby segregating markers. Within a species, genome-wide variation in recombination rates can be determined by following the inheritance of such genetic markers in crosses or pedigrees (7-10) or by examining patterns of linkage disequilibrium within a population (11-15). Population-based approaches have the advantage that in diverse populations, hundreds of thousands of historical recombination events can be sampled, compared with only hundreds in the largest pedigrees.The monkeyflower Mimulus guttatus has an exceptionally high nucleotide diversity, which makes it a particularly appealing system for characterizing the boundaries of recombination events. We observed an average pairwise n...

Polarized gene conversion at the bz locus of maize

“…A recent genome-wide study also detected positional recombination polarity in a flowering plant. In Mimulus genes with five or more exons, the average historical recombination was highest in the first exon and decayed with distance from the start codon (34).…”

High-Resolution Mapping of Crossover Events in the Hexaploid Wheat Genome Suggests a Universal Recombination Mechanism

“…P-values are 0.05 (*) and 0.01 (**). (Hellsten et al 2013), or Drosophila (Smukowski Heil et al 2015). Specific recombination intensities were different depending on the collection used which could be attributed to the difference in LD patterns at fine scale in the two populations, or differences arising from the complex evolutionary histories of the two genetic pools we used.…”

“…To compare contemporary and ancestral CO frequencies and hotspots in our wheat scaffolds, we applied coalescent theory (Choi et al 2013;Hellsten et al 2013) to a SNP data set generated from our two Asian and European populations. We used PHASE 2.1.1 (Li and Stephens 2003;Crawford et al 2004) to estimate the background recombination rate parameter, r, and to infer hotspot position between pairs of SNPs using l. Presence/absence of polymorphism was encoded using the available multi-allelic function, while other SNPs were encoded as biallelic markers as described in the PHASE user manual.…”

“…This switch can be detected by genotyping the progenies derived from biparental or multi-parental crosses (for a review see Huang et al 2015) but is limited by a constrained number of COs (Darvasi et al 1993). Statistical approaches were also developed to estimate the population recombination parameter, r, and to computationally infer genome-wide, population-averaged recombination rates (McVean et al 2002(McVean et al , 2004Li and Stephens 2003;Slatkin 2008;Hellsten et al 2013;Smukowski Heil et al 2015). These approaches, also termed "coalescent analysis," rely on linkage disequilibrium (LD) patterns in populations which represent a nonrandom association of alleles at different loci (Lewontin and Kojima 1960).…”

“…In plants, coalescent theory was successfully applied to generate maps of CO frequency and hotspots in monkey flower (Mimulus guttatus; Hellsten et al 2013) and in Arabidopsis thaliana, (Choi et al 2013). In Mimulus, a collection of 98 individuals was used to precisely locate 414,734 CO-or geneconversion events, among which 3235 were highly reliable recombination hotspots and 13,000 were considered bona fide COs.…”