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High-resolution mapping of meiotic crossovers and non-crossovers in yeast

Abstract

Meiotic recombination has a central role in the evolution of sexually reproducing organisms. The two recombination outcomes, crossover and non-crossover, increase genetic diversity, but have the potential to homogenize alleles by gene conversion. Whereas crossover rates vary considerably across the genome, non-crossovers and gene conversions have only been identified in a handful of loci. To examine recombination genome wide and at high spatial resolution, we generated maps of crossovers, crossover-associated gene conversion and non-crossover gene conversion using dense genetic marker data collected from all four products of fifty-six yeast (Saccharomyces cerevisiae) meioses. Our maps reveal differences in the distributions of crossovers and non-crossovers, showing more regions where either crossovers or non-crossovers are favoured than expected by chance. Furthermore, we detect evidence for interference between crossovers and non-crossovers, a phenomenon previously only known to occur between crossovers. Up to 1% of the genome of each meiotic product is subject to gene conversion in a single meiosis, with detectable bias towards GC nucleotides. To our knowledge the maps represent the first high-resolution, genome-wide characterization of the multiple outcomes of recombination in any organism. In addition, because non-crossover hotspots create holes of reduced linkage within haplotype blocks, our results stress the need to incorporate non-crossovers into genetic linkage analysis.

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Figure 1: High-resolution mapping of meiotic recombination along the yeast genome.
Figure 2: Crossover and non-crossover rates along chromosome I and their effect on recombination fraction (rf).
Figure 3: Comparison of DSB and recombination rates along chromosome III.
Figure 4: Association between gene expression and recombination activity.
Figure 5: Meiotic recombination in msh4 and mms4 strains.

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ArrayExpress

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Raw data are available from ArrayExpress (http://www.ebi.ac.uk/arrayexpress) under accession number E-TABM-470.

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Acknowledgements

We thank S. Clauder-Münster, M. Granovskaia, M. Sieber, T. Bähr-Ivacevic, M. Nguyen, V. Benes, Z. Xu, L. Ettwiller, P. McGettigan and the EMBL Genomics Core Facility for technical help; M. Knop for discussions; A. Akhtar, A. Ladurner, A. De Luna and M. Knop for critical comments on the manuscript; E. Louis, R. Durbin and D. Carter for making data from the Saccharomyces Genome Resequencing Project available; and the contributors to the Bioconductor (http://www.bioconductor.org) and R (http://www.R-project.org) projects for making their software available. This work was supported by grants to L.M.S. from the National Institutes of Health and the Deutsche Forschungsgemeinschaft, and to W.H. from the Human Frontier Science Program; and by a Darwin Trust’s Jeff Shell Scholarship awarded to E.M.

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Correspondence to Lars M. Steinmetz.

Supplementary information

Supplementary Information 1

This file contains Supplementary Methods, Supplementary Discussion, Supplementary Figures 1-14 with Legends and Supplementary Tables 1-5. (PDF 4570 kb)

Supplementary Information 2

This archive contains Supplementary Data, including whole genome tetrad plots, genotype calls for all spores, genotype summary statistics for wildtype spores, inferred recombination events, CO, NCO and overall recombination hot spots, and intermarker interval statistics. The details for files in this folder are given in Supplementary Table 5 within the Supplementary Information file. (ZIP 6762 kb)

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Mancera, E., Bourgon, R., Brozzi, A. et al. High-resolution mapping of meiotic crossovers and non-crossovers in yeast. Nature 454, 479–485 (2008). https://doi.org/10.1038/nature07135

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