DNA sequence differences are determinants of meiotic recombination outcome

Simon David Brown; Samantha Jacqueline Mpaulo; Mimi Nwakaego Asogwa; Marie Jézéquel; Matthew C Whitby; Alexander Lorenz

doi:10.1101/568543

DNA sequence differences are determinants of meiotic recombination outcome

Simon David Brown, Samantha Jacqueline Mpaulo, Mimi Nwakaego Asogwa, Marie Jézéquel, Matthew C Whitby, Alexander Lorenz^* (Corresponding Author)

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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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 Schizosaccharomyces pombe, 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). 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 MutSα-MutLα 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 language	English
Article number	16446
Number of pages	10
Journal	Scientific Reports
Volume	9
DOIs	https://doi.org/10.1101/568543 https://doi.org/10.1038/s41598-019-52907-x
Publication status	Published - 11 Nov 2019

Bibliographical note

Acknowledgements
We are grateful to Jürg Bähler, Edgar Hartsuiker, Franz Klein, Jürg Kohli, Josef Loidl, Kim Nasmyth, Fekret Osman, Gerald R. Smith, Walter W. Steiner, and the National BioResource Project (NBRP) Japan for providing materials, and to C. Bryer, A. Mehats, and H. Rickman for technical assistance. This work was supported by the Biotechnology and Biological Sciences Research Council UK (BBSRC) [grant numbers BB/F016964/1, BB/M010996/1], the University of Aberdeen (College of Life Sciences and Medicine Start-up grant to AL), and the Wellcome Trust (Programme grant to MCW) [grant number 090767/Z/09/Z].

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DNA sequence differences are determinants of meiotic recombination outcome
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Cite this

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title = "DNA sequence differences are determinants of meiotic recombination outcome",

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 Schizosaccharomyces pombe, 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). 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 MutSα-MutLα 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.",

author = "Brown, {Simon David} and Mpaulo, {Samantha Jacqueline} and Asogwa, {Mimi Nwakaego} and Marie J{\'e}z{\'e}quel and Whitby, {Matthew C} and Alexander Lorenz",

note = "Acknowledgements We are grateful to J{\"u}rg B{\"a}hler, Edgar Hartsuiker, Franz Klein, J{\"u}rg Kohli, Josef Loidl, Kim Nasmyth, Fekret Osman, Gerald R. Smith, Walter W. Steiner, and the National BioResource Project (NBRP) Japan for providing materials, and to C. Bryer, A. Mehats, and H. Rickman for technical assistance. This work was supported by the Biotechnology and Biological Sciences Research Council UK (BBSRC) [grant numbers BB/F016964/1, BB/M010996/1], the University of Aberdeen (College of Life Sciences and Medicine Start-up grant to AL), and the Wellcome Trust (Programme grant to MCW) [grant number 090767/Z/09/Z].",

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T1 - DNA sequence differences are determinants of meiotic recombination outcome

AU - Brown, Simon David

AU - Mpaulo, Samantha Jacqueline

AU - Asogwa, Mimi Nwakaego

AU - Jézéquel, Marie

AU - Whitby, Matthew C

AU - Lorenz, Alexander

N1 - Acknowledgements We are grateful to Jürg Bähler, Edgar Hartsuiker, Franz Klein, Jürg Kohli, Josef Loidl, Kim Nasmyth, Fekret Osman, Gerald R. Smith, Walter W. Steiner, and the National BioResource Project (NBRP) Japan for providing materials, and to C. Bryer, A. Mehats, and H. Rickman for technical assistance. This work was supported by the Biotechnology and Biological Sciences Research Council UK (BBSRC) [grant numbers BB/F016964/1, BB/M010996/1], the University of Aberdeen (College of Life Sciences and Medicine Start-up grant to AL), and the Wellcome Trust (Programme grant to MCW) [grant number 090767/Z/09/Z].

PY - 2019/11/11

Y1 - 2019/11/11

N2 - 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 Schizosaccharomyces pombe, 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). 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 MutSα-MutLα 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.

AB - 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 Schizosaccharomyces pombe, 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). 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 MutSα-MutLα 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.

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SN - 2045-2322

VL - 9

JO - Scientific Reports

JF - Scientific Reports

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ER -

DNA sequence differences are determinants of meiotic recombination outcome

Abstract

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