The effect of DNA polymorphisms and natural variation on crossover hotspot activity in Arabidopsis hybrids

Abstract

In hybrid organisms, genetically divergent homologous chromosomes pair and recombine during meiosis; however, the effect of specific types of polymorphisms on crossover is poorly understood. Here, to analyze this in Arabidopsis, we develop the seed-typing method that enables the massively parallel fine-mapping of crossovers by sequencing. We show that structural variants, observed in one of the generated intervals, do not change crossover frequency unless they are located directly within crossover hotspots. Both natural and Cas9-induced deletions result in lower hotspot activity but are not compensated by increases in immediately adjacent hotspots. To examine the effect of single nucleotide polymorphisms on crossover formation, we analyze hotspot activity in mismatch detection-deficient msh2 mutants. Surprisingly, polymorphic hotspots show reduced activity in msh2. In lines where only the hotspot-containing interval is heterozygous, crossover numbers increase above those in the inbred (homozygous). We conclude that MSH2 shapes crossover distribution by stimulating hotspot activity at polymorphic regions.

Meiotic recombination dynamics in plants with repeat-based holocentromeres shed light on the primary drivers of crossover patterning

“…A recent study showed that the megabase-scale CO landscape in A. thaliana is mostly explained by association with (epi)genetic marks beyond a centromere effect, with open chromatin states showing the highest positive correlation with CO formation 15 . While single nucleotide polymorphisms only showed a rather local effect on CO positioning 15,62 . In contrast to these organisms, we could only find correlation of CO positioning with centromere and (epi)genetic features at a very fine-scale.…”

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“…Crossover tactics include discrete recombination, intermediary recombination, and linear recombination, which are actual crossovers, and binary crossovers . In this study, we offer a novel crossover technique for bringing on new hires [19]. In genetic algorithms, the crossover is typically performed by selecting a crossover point along the chromosome and swapping genetic material between two parent individuals to create one or more offspring individuals.…”

MSH2 stimulates interfering and inhibits non-interfering crossovers in response to genetic polymorphism

“…In eukaryotes, heterodimers of bacterial MutS homologues (MSHs) that bind mismatched bases are responsible for detecting interhomolog polymorphism 54,58,59 . All MSH dimers involved in mismatch detection are assumed to contain the MSH2 protein 49,50,54,[58][59][60] . Therefore, we investigated whether inactivation of MSH2 would increase the fertility of fancm zip4 Col/Ler hybrids.…”

“…The msh2-1 T-DNA insertion line (SALK_002708) and Arabidopsis accessions Col, Ler and Ct were obtained from the Nottingham Arabidopsis Stock Centre (NASC). The msh2-2, msh2-3, msh2-4, msh2-5 (in Col/Ct recombinant lines) and msh2-6 (in Ler−0) deletion mutants were previously generated in our laboratory via CRISPR/ Cas9 mutagenesis 49,50 , as well as Ler zip4-3 mutant generated in this study. The HEI10-OE line corresponds to transgenic line "C2", previously described in ref.…”

“…For example, the juxtaposition of heterozygous and homozygous regions stimulates crossover in the heterozygous region 48 . This effect is specific to the ZMM pathway and also depends on MSH2 49,50 . MSH2 is a key subunit of complexes that detect base mismatches occurring in somatic cells, as a consequence of replication errors [51][52][53] .…”