DNA sequence differences are determinants of meiotic recombination outcome

Simon D. Brown, Samantha J. Mpaulo, Mimi N. Asogwa, Marie Jézéquel, Charlotte Audoynaud, Matthew C. Whitby, Alexander Lorenz

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Abstract

Meiotic recombination is essential for producing healthy gametes, and also generates genetic diversity. DNA double-strand break (DSB) formation is the initiating step of meiotic recombination, producing, among other outcomes, crossovers between homologous chromosomes (homologs), which provide physical links to guide accurate chromosome segregation. The parameters influencing DSB position and repair are thus crucial determinants of reproductive success and genetic diversity. Using <i>Schizosaccharomyces pombe</i>, we show that the distance between sequence polymorphisms across homologs has a strong impact on meiotic recombination rate. The closer the sequence polymorphisms are to each other across the homologs the fewer recombination events were observed. In the immediate vicinity of DSBs sequence polymorphisms affect the frequency of intragenic recombination events (gene conversions and intragenic crossovers). Additionally, and unexpectedly, the crossover rate of flanking markers tens of kilobases away from the sequence polymorphisms was affected by their relative position to each other amongst the progeny having undergone intragenic recombination. A major regulator of this distance-dependent effect is the MutS&alpha;-MutL&alpha; complex consisting of Msh2, Msh6, Mlh1, and Pms1. Additionally, the DNA helicases Rqh1 and Fml1 shape recombination frequency, although the effects seen here are largely independent of the relative position of the sequence polymorphisms.
Original languageEnglish
Article number568543
Number of pages16
JournalbioRxiv
DOIs
Publication statusAccepted/In press - 5 Mar 2019

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Genetic Recombination
Chromosomes
DNA Helicases
Gene Conversion
Chromosome Segregation
Double-Stranded DNA Breaks
Schizosaccharomyces
Germ Cells

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Brown, S. D., Mpaulo, S. J., Asogwa, M. N., Jézéquel, M., Audoynaud, C., Whitby, M. C., & Lorenz, A. (Accepted/In press). DNA sequence differences are determinants of meiotic recombination outcome. bioRxiv, [568543]. https://doi.org/10.1101/568543

DNA sequence differences are determinants of meiotic recombination outcome. / Brown, Simon D.; Mpaulo, Samantha J.; Asogwa, Mimi N.; Jézéquel, Marie; Audoynaud, Charlotte; Whitby, Matthew C.; Lorenz, Alexander.

In: bioRxiv, 05.03.2019.

Research output: Contribution to journalArticle

Brown, SD, Mpaulo, SJ, Asogwa, MN, Jézéquel, M, Audoynaud, C, Whitby, MC & Lorenz, A 2019, 'DNA sequence differences are determinants of meiotic recombination outcome' bioRxiv. https://doi.org/10.1101/568543
Brown SD, Mpaulo SJ, Asogwa MN, Jézéquel M, Audoynaud C, Whitby MC et al. DNA sequence differences are determinants of meiotic recombination outcome. bioRxiv. 2019 Mar 5. 568543. https://doi.org/10.1101/568543
Brown, Simon D. ; Mpaulo, Samantha J. ; Asogwa, Mimi N. ; Jézéquel, Marie ; Audoynaud, Charlotte ; Whitby, Matthew C. ; Lorenz, Alexander. / DNA sequence differences are determinants of meiotic recombination outcome. In: bioRxiv. 2019.
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