Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Divergence and conservation of the meiotic recombination machinery

Abstract

Sexually reproducing eukaryotes use recombination between homologous chromosomes to promote chromosome segregation during meiosis. Meiotic recombination is almost universally conserved in its broad strokes, but specific molecular details often differ considerably between taxa, and the proteins that constitute the recombination machinery show substantial sequence variability. The extent of this variation is becoming increasingly clear because of recent increases in genomic resources and advances in protein structure prediction. We discuss the tension between functional conservation and rapid evolutionary change with a focus on the proteins that are required for the formation and repair of meiotic DNA double-strand breaks. We highlight phylogenetic relationships on different time scales and propose that this remarkable evolutionary plasticity is a fundamental property of meiotic recombination that shapes our understanding of molecular mechanisms in reproductive biology.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Recombination is essential for haploidization during gametogenesis.
Fig. 2: Examples of evolutionarily plastic structure and/or function.
Fig. 3: Selective pressures that might shape the evolution of meiotic recombination genes.

References

  1. de Massy, B. Initiation of meiotic recombination: how and where? Conservation and specificities among eukaryotes. Annu. Rev. Genet. 47, 563–599 (2013).

    Article  PubMed  Google Scholar 

  2. Keeney, S. Mechanism and control of meiotic recombination initiation. Curr. Top. Dev. Biol. 52, 1–53 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Hunter, N. Meiotic recombination: the essence of heredity. Cold Spring Harb. Perspect. Biol. 7, a016618 (2015).

    Article  PubMed Central  PubMed  Google Scholar 

  4. Hassold, T. J. & Hunt, P. A. Missed connections: recombination and human aneuploidy. Prenat. Diagn. 41, 584–590 (2021).

    Article  PubMed  Google Scholar 

  5. Boekhout, M. et al. REC114 partner ANKRD31 controls number, timing, and location of meiotic DNA breaks. Mol. Cell 74, 1053–1068.e1058 (2019).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Dapper, A. L. & Payseur, B. A. Molecular evolution of the meiotic recombination pathway in mammals. Evolution 73, 2368–2389 (2019). This study uses molecular evolution analyses to systematically characterize components of the mammalian recombination machinery and finds evidence for rapid evolution in key components.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Keeney, S. Spo11 and the formation of DNA double-strand breaks in meiosis. Genome Dyn. Stab. 2, 81–123 (2008).

    Article  PubMed Central  PubMed  Google Scholar 

  8. Murat, F. et al. The molecular evolution of spermatogenesis across mammals. Nature 613, 308–316 (2023). Using single-nucleus transcriptomics across different mammalian species, this study characterizes changes in spermatogenesis at unprecedented resolution.

    Article  CAS  PubMed  Google Scholar 

  9. Malik, S. B., Ramesh, M. A., Hulstrand, A. M. & Logsdon, J. M. Jr. Protist homologs of the meiotic Spo11 gene and topoisomerase VI reveal an evolutionary history of gene duplication and lineage-specific loss. Mol. Biol. Evol. 24, 2827–2841 (2007). Using degenerate PCR and database searches this study identifies homologues of SPO11 and TOP6BL in protists.

    Article  CAS  PubMed  Google Scholar 

  10. Keeney, S., Giroux, C. N. & Kleckner, N. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell 88, 375–384 (1997).

    Article  CAS  PubMed  Google Scholar 

  11. Bergerat, A. et al. An atypical topoisomerase II from Archaea with implications for meiotic recombination. Nature 386, 414–417 (1997).

    Article  CAS  PubMed  Google Scholar 

  12. Robert, T. et al. The TOPOVIB-like protein family is required for meiotic DNA double-strand break formation. Science 351, 943–949 (2016). This study identified the SPO11 partner TOPOVIBL in mouse.

    Article  CAS  PubMed  Google Scholar 

  13. Vrielynck, N. et al. A DNA topoisomerase VI-like complex initiates meiotic recombination. Science 351, 939–943 (2016). This study identified the SPO11 partner TOPOVIBL in Arabidopsis.

    Article  CAS  PubMed  Google Scholar 

  14. Jumper, J. et al. Highly accurate protein structure prediction with AlphaFold. Nature 596, 583–589 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Fraune, J., Wiesner, M. & Benavente, R. The synaptonemal complex of basal metazoan hydra: more similarities to vertebrate than invertebrate meiosis model organisms. J. Genet. Genomics 41, 107–115 (2014).

    Article  PubMed  Google Scholar 

  16. Loidl, J. Conservation and variability of meiosis across the eukaryotes. Annu. Rev. Genet. 50, 293–316 (2016).

    Article  CAS  PubMed  Google Scholar 

  17. Ishiguro, K. I. The cohesin complex in mammalian meiosis. Genes Cells 24, 6–30 (2019).

    Article  CAS  PubMed  Google Scholar 

  18. Zickler, D. & Kleckner, N. Recombination, pairing, and synapsis of homologs during meiosis. Cold Spring Harb. Perspect. Biol. 7, a016626 (2015).

    Article  PubMed Central  PubMed  Google Scholar 

  19. Longhese, M. P., Bonetti, D., Guerini, I., Manfrini, N. & Clerici, M. DNA double-strand breaks in meiosis: checking their formation, processing and repair. DNA Repair 8, 1127–1138 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Gerton, J. L. & Hawley, R. S. Homologous chromosome interactions in meiosis: diversity amidst conservation. Nat. Rev. Genet. 6, 477–487 (2005).

    Article  CAS  PubMed  Google Scholar 

  21. de Boer, E. & Heyting, C. The diverse roles of transverse filaments of synaptonemal complexes in meiosis. Chromosoma 115, 220–234 (2006).

    Article  PubMed  Google Scholar 

  22. Subramanian, V. V. & Hochwagen, A. The meiotic checkpoint network: step-by-step through meiotic prophase. Cold Spring Harb. Perspect. Biol. 6, a016675 (2014).

    Article  PubMed Central  PubMed  Google Scholar 

  23. Ivanov, E. L., Korolev, V. G. & Fabre, F. XRS2, a DNA repair gene of Saccharomyces cerevisiae, is needed for meiotic recombination. Genetics 132, 651–664 (1992).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Engebrecht, J., Hirsch, J. & Roeder, G. S. Meiotic gene conversion and crossing over: their relationship to each other and to chromosome synapsis and segregation. Cell 62, 927–937 (1990).

    Article  CAS  PubMed  Google Scholar 

  25. Malone, R. E. et al. Isolation of mutants defective in early steps of meiotic recombination in the yeast Saccharomyces cerevisiae. Genetics 128, 79–88 (1991).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Menees, T. M. & Roeder, G. S. MEI4, a yeast gene required for meiotic recombination. Genetics 123, 675–682 (1989).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Gardiner, J. M., Bullard, S. A., Chrome, C. & Malone, R. E. Molecular and genetic analysis of REC103, an early meiotic recombination gene in yeast. Genetics 146, 1265–1274 (1997).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Bhargava, J., Engebrecht, J. & Roeder, G. S. The rec102 mutant of yeast is defective in meiotic recombination and chromosome synapsis. Genetics 130, 59–69 (1992).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Galbraith, A. M. & Malone, R. E. Characterization of REC104, a gene required for early meiotic recombination in the yeast Saccharomyces cerevisiae. Dev. Genet. 13, 392–402 (1992).

    Article  CAS  PubMed  Google Scholar 

  30. Johzuka, K. & Ogawa, H. Interaction of Mre11 and Rad50: two proteins required for DNA repair and meiosis-specific double-strand break formation in Saccharomyces cerevisiae. Genetics 139, 1521–1532 (1995).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Game, J. C., Zamb, T. J., Braun, R. J., Resnick, M. & Roth, R. M. The role of radiation (rad) genes in meiotic recombination in yeast. Genetics 94, 51–68 (1980).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Jiao, K., Salem, L. & Malone, R. Support for a meiotic recombination initiation complex: interactions among Rec102p, Rec104p, and Spo11p. Mol. Cell Biol. 23, 5928–5938 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  33. Kee, K. & Keeney, S. Functional interactions between SPO11 and REC102 during initiation of meiotic recombination in Saccharomyces cerevisiae. Genetics 160, 111–122 (2002).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Kee, K., Protacio, R. U., Arora, C. & Keeney, S. Spatial organization and dynamics of the association of Rec102 and Rec104 with meiotic chromosomes. EMBO J. 23, 1815–1824 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Claeys Bouuaert, C. et al. Structural and functional characterization of the Spo11 core complex. Nat. Struct. Mol. Biol. 28, 92–102 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Arora, C., Kee, K., Maleki, S. & Keeney, S. Antiviral protein Ski8 is a direct partner of Spo11 in meiotic DNA break formation, independent of its cytoplasmic role in RNA metabolism. Mol. Cell 13, 549–559 (2004).

    Article  CAS  PubMed  Google Scholar 

  37. Claeys Bouuaert, C. et al. DNA-driven condensation assembles the meiotic DNA break machinery. Nature 592, 144–149 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  38. Neale, M. J., Pan, J. & Keeney, S. Endonucleolytic processing of covalent protein-linked DNA double-strand breaks. Nature 436, 1053–1057 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Garcia, V., Phelps, S. E., Gray, S. & Neale, M. J. Bidirectional resection of DNA double-strand breaks by Mre11 and Exo1. Nature 479, 241–244 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Prinz, S., Amon, A. & Klein, F. Isolation of COM1, a new gene required to complete meiotic double-strand break-induced recombination in Saccharomyces cerevisiae. Genetics 146, 781–795 (1997).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. McKee, A. H. & Kleckner, N. A general method for identifying recessive diploid-specific mutations in Saccharomyces cerevisiae, its application to the isolation of mutants blocked at intermediate stages of meiotic prophase and characterization of a new gene SAE2. Genetics 146, 797–816 (1997).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Chin, G. M. & Villeneuve, A. M. C. elegans mre-11 is required for meiotic recombination and DNA repair but is dispensable for the meiotic G(2) DNA damage checkpoint. Genes Dev. 15, 522–534 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  43. Goodyer, W. et al. HTP-3 links DSB formation with homolog pairing and crossing over during C. elegans meiosis. Dev. Cell 14, 263–274 (2008).

    Article  CAS  PubMed  Google Scholar 

  44. Yin, Y. & Smolikove, S. Impaired resection of meiotic double-strand breaks channels repair to nonhomologous end joining in Caenorhabditis elegans. Mol. Cell Biol. 33, 2732–2747 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Bishop, D. K., Park, D., Xu, L. & Kleckner, N. DMC1: a meiosis-specific yeast homolog of E. coli recA required for recombination, synaptonemal complex formation, and cell cycle progression. Cell 69, 439–456 (1992).

    Article  CAS  PubMed  Google Scholar 

  46. Shinohara, A., Ogawa, H. & Ogawa, T. Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein. Cell 69, 457–470 (1992).

    Article  CAS  PubMed  Google Scholar 

  47. Lin, Z., Kong, H., Nei, M. & Ma, H. Origins and evolution of the recA/RAD51 gene family: evidence for ancient gene duplication and endosymbiotic gene transfer. Proc. Natl Acad. Sci. USA 103, 10328–10333 (2006). An evolutionary characterization of the RAD51 gene family.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  48. Tang, S., Wu, M. K. Y., Zhang, R. & Hunter, N. Pervasive and essential roles of the Top3-Rmi1 decatenase orchestrate recombination and facilitate chromosome segregation in meiosis. Mol. Cell 57, 607–621 (2015).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Kaur, H., De Muyt, A. & Lichten, M. Top3-Rmi1 DNA single-strand decatenase is integral to the formation and resolution of meiotic recombination intermediates. Mol. Cell 57, 583–594 (2015).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  50. De Muyt, A. et al. BLM helicase ortholog Sgs1 is a central regulator of meiotic recombination intermediate metabolism. Mol. Cell 46, 43–53 (2012).

    Article  PubMed Central  PubMed  Google Scholar 

  51. Amin, A. D., Chaix, A. B., Mason, R. P., Badge, R. M. & Borts, R. H. The roles of the Saccharomyces cerevisiae RecQ helicase SGS1 in meiotic genome surveillance. PLoS ONE 5, e15380 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  52. Oh, S. D. et al. BLM ortholog, Sgs1, prevents aberrant crossing-over by suppressing formation of multichromatid joint molecules. Cell 130, 259–272 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  53. Fasching, C. L., Cejka, P., Kowalczykowski, S. C. & Heyer, W. D. Top3-Rmi1 dissolve Rad51-mediated D loops by a topoisomerase-based mechanism. Mol. Cell 57, 595–606 (2015).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  54. Sandhu, R. et al. DNA helicase Mph1(FANCM) ensures meiotic recombination between parental chromosomes by dissociating precocious displacement loops. Dev. Cell 53, 458–472 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Sasanuma, H. et al. Srs2 helicase prevents the formation of toxic DNA damage during late prophase I of yeast meiosis. Chromosoma 128, 453–471 (2019).

    Article  CAS  PubMed  Google Scholar 

  56. Palladino, F. & Klein, H. L. Analysis of mitotic and meiotic defects in Saccharomyces cerevisiae SRS2 DNA helicase mutants. Genetics 132, 23–37 (1992).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  57. Zakharyevich, K., Tang, S., Ma, Y. & Hunter, N. Delineation of joint molecule resolution pathways in meiosis identifies a crossover-specific resolvase. Cell 149, 334–347 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  58. Zakharyevich, K. et al. Temporally and biochemically distinct activities of Exo1 during meiosis: double-strand break resection and resolution of double Holliday junctions. Mol. Cell 40, 1001–1015 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  59. Cannavo, E. et al. Regulation of the MLH1-MLH3 endonuclease in meiosis. Nature 586, 618–622 (2020).

    Article  CAS  PubMed  Google Scholar 

  60. Nishant, K. T., Plys, A. J. & Alani, E. A mutation in the putative MLH3 endonuclease domain confers a defect in both mismatch repair and meiosis in Saccharomyces cerevisiae. Genetics 179, 747–755 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  61. Argueso, J. L. et al. Analysis of conditional mutations in the Saccharomyces cerevisiae MLH1 gene in mismatch repair and in meiotic crossing over. Genetics 160, 909–921 (2002).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  62. Rockmill, B., Fung, J. C., Branda, S. S. & Roeder, G. S. The Sgs1 helicase regulates chromosome synapsis and meiotic crossing over. Curr. Biol. 13, 1954–1962 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Ross-Macdonald, P. & Roeder, G. S. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Cell 79, 1069–1080 (1994).

    Article  CAS  PubMed  Google Scholar 

  64. Hollingsworth, N. M., Ponte, L. & Halsey, C. MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes Dev. 9, 1728–1739 (1995).

    Article  CAS  PubMed  Google Scholar 

  65. Mazina, O. M., Mazin, A. V., Nakagawa, T., Kolodner, R. D. & Kowalczykowski, S. C. Saccharomyces cerevisiae Mer3 helicase stimulates 3′-5′ heteroduplex extension by Rad51; implications for crossover control in meiotic recombination. Cell 117, 47–56 (2004).

    Article  CAS  PubMed  Google Scholar 

  66. De Muyt, A. et al. A meiotic XPF-ERCC1-like complex recognizes joint molecule recombination intermediates to promote crossover formation. Genes Dev. 32, 283–296 (2018).

    Article  PubMed Central  PubMed  Google Scholar 

  67. Chua, P. R. & Roeder, G. S. Zip2, a meiosis-specific protein required for the initiation of chromosome synapsis. Cell 93, 349–359 (1998).

    Article  CAS  PubMed  Google Scholar 

  68. Börner, G. V., Kleckner, N. & Hunter, N. Crossover/noncrossover differentiation, synaptonemal complex formation, and regulatory surveillance at the leptotene/zygotene transition of meiosis. Cell 117, 29–45 (2004).

    Article  PubMed  Google Scholar 

  69. Agarwal, S. & Roeder, G. S. Zip3 provides a link between recombination enzymes and synaptonemal complex proteins. Cell 102, 245–255 (2000).

    Article  CAS  PubMed  Google Scholar 

  70. Berchowitz, L. E. & Copenhaver, G. P. Genetic interference: don’t stand so close to me. Curr. Genomics 11, 91–102 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  71. Argueso, J. L., Wanat, J., Gemici, Z. & Alani, E. Competing crossover pathways act during meiosis in Saccharomyces cerevisiae. Genetics 168, 1805–1816 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  72. de los Santos, T. et al. The Mus81/Mms4 endonuclease acts independently of double-Holliday junction resolution to promote a distinct subset of crossovers during meiosis in budding yeast. Genetics 164, 81–94 (2003).

    Article  Google Scholar 

  73. de los Santos, T., Loidl, J., Larkin, B. & Hollingsworth, N. M. A role for MMS4 in the processing of recombination intermediates during meiosis in Saccharomyces cerevisiae. Genetics 159, 1511–1525 (2001).

    Article  Google Scholar 

  74. Lin, Y. & Smith, G. R. Transient, meiosis-induced expression of the rec6 and rec12 genes of Schizosaccharomyces pombe. Genetics 136, 769–779 (1994).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  75. Cervantes, M. D., Farah, J. A. & Smith, G. R. Meiotic DNA breaks associated with recombination in S. pombe. Mol. Cell 5, 883–888 (2000).

    Article  CAS  PubMed  Google Scholar 

  76. Miyoshi, T. et al. A central coupler for recombination initiation linking chromosome architecture to S phase checkpoint. Mol. Cell 47, 722–733 (2012).

    Article  CAS  PubMed  Google Scholar 

  77. Evans, D. H., Li, Y. F., Fox, M. E. & Smith, G. R. A WD repeat protein, Rec14, essential for meiotic recombination in Schizosaccharomyces pombe. Genetics 146, 1253–1264 (1997).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  78. Lin, Y. & Smith, G. R. An intron-containing meiosis-induced recombination gene, rec15, of Schizosaccharomyces pombe. Mol. Microbiol. 17, 439–448 (1995).

    Article  CAS  PubMed  Google Scholar 

  79. Bonfils, S., Rozalen, A. E., Smith, G. R., Moreno, S. & Martin-Castellanos, C. Functional interactions of Rec24, the fission yeast ortholog of mouse Mei4, with the meiotic recombination-initiation complex. J. Cell Sci. 124, 1328–1338 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  80. Molnar, M. et al. Characterization of rec7, an early meiotic recombination gene in Schizosaccharomyces pombe. Genetics 157, 519–532 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  81. Steiner, S., Kohli, J. & Ludin, K. Functional interactions among members of the meiotic initiation complex in fission yeast. Curr. Genet. 56, 237–249 (2010).

    Article  CAS  PubMed  Google Scholar 

  82. Young, J. A., Hyppa, R. W. & Smith, G. R. Conserved and nonconserved proteins for meiotic DNA breakage and repair in yeasts. Genetics 167, 593–605 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. Gregan, J. et al. Novel genes required for meiotic chromosome segregation are identified by a high-throughput knockout screen in fission yeast. Curr. Biol. 15, 1663–1669 (2005).

    Article  CAS  PubMed  Google Scholar 

  84. Thompson, E. A. & Roeder, G. S. Expression and DNA sequence of RED1, a gene required for meiosis I chromosome segregation in yeast. Mol. Gen. Genet. 218, 293–301 (1989).

    Article  CAS  PubMed  Google Scholar 

  85. Rockmill, B. & Roeder, G. S. Meiosis in asynaptic yeast. Genetics 126, 563–574 (1990).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  86. Tavassoli, M., Shayeghi, M., Nasim, A. & Watts, F. Z. Cloning and characterisation of the Schizosaccharomyces pombe rad32 gene: a gene required for repair of double strand breaks and recombination. Nucleic Acids Res. 23, 383–388 (1995).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  87. Davidson, M. K., Young, N. P., Glick, G. G. & Wahls, W. P. Meiotic chromosome segregation mutants identified by insertional mutagenesis of fission yeast Schizosaccharomyces pombe; tandem-repeat, single-site integrations. Nucleic Acids Res. 32, 4400–4410 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  88. Hartsuiker, E. et al. Ctp1CtIP and Rad32Mre11 nuclease activity are required for Rec12Spo11 removal, but Rec12Spo11 removal is dispensable for other MRN-dependent meiotic functions. Mol. Cell Biol. 29, 1671–1681 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Milman, N., Higuchi, E. & Smith, G. R. Meiotic DNA double-strand break repair requires two nucleases, MRN and Ctp1, to produce a single size class of Rec12 (Spo11)-oligonucleotide complexes. Mol. Cell Biol. 29, 5998–6005 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Rothenberg, M., Kohli, J. & Ludin, K. Ctp1 and the MRN-complex are required for endonucleolytic Rec12 removal with release of a single class of oligonucleotides in fission yeast. PLoS Genet. 5, e1000722 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  91. Farah, J. A., Cromie, G. A. & Smith, G. R. Ctp1 and exonuclease 1, alternative nucleases regulated by the MRN complex, are required for efficient meiotic recombination. Proc. Natl Acad. Sci. USA 106, 9356–9361 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  92. Grishchuk, A. L. & Kohli, J. Five RecA-like proteins of Schizosaccharomyces pombe are involved in meiotic recombination. Genetics 165, 1031–1043 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  93. Lorenz, A. et al. The fission yeast FANCM ortholog directs non-crossover recombination during meiosis. Science 336, 1585–1588 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  94. Cromie, G. A., Hyppa, R. W. & Smith, G. R. The fission yeast BLM homolog Rqh1 promotes meiotic recombination. Genetics 179, 1157–1167 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  95. Hope, J. C. et al. Mus81-Eme1-dependent and -independent crossovers form in mitotic cells during double-strand break repair in Schizosaccharomyces pombe. Mol. Cell Biol. 27, 3828–3838 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  96. Boddy, M. N. et al. Mus81-Eme1 are essential components of a Holliday junction resolvase. Cell 107, 537–548 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Cromie, G. A. et al. Single Holliday junctions are intermediates of meiotic recombination. Cell 127, 1167–1178 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  98. McKim, K. S. & Hayashi-Hagihara, A. mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: evidence that the mechanism for initiating meiotic recombination is conserved. Genes Dev. 12, 2932–2942 (1998).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  99. Liu, H., Jang, J. K., Kato, N. & McKim, K. S. mei-P22 encodes a chromosome-associated protein required for the initiation of meiotic recombination in Drosophila melanogaster. Genetics 162, 245–258 (2002).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  100. Lake, C. M. et al. Vilya, a component of the recombination nodule, is required for meiotic double-strand break formation in Drosophila. eLife 4, e08287 (2015).

    Article  PubMed Central  PubMed  Google Scholar 

  101. Lake, C. M., Nielsen, R. J. & Hawley, R. S. The Drosophila zinc finger protein trade embargo is required for double strand break formation in meiosis. PLoS Genet. 7, e1002005 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  102. Lake, C. M. et al. Narya, a RING finger domain-containing protein, is required for meiotic DNA double-strand break formation and crossover maturation in Drosophila melanogaster. PLoS Genet. 15, e1007886 (2019).

    Article  PubMed Central  PubMed  Google Scholar 

  103. Digilio, F. A., Pannuti, A., Lucchesi, J. C., Furia, M. & Polito, L. C. Tosca: a Drosophila gene encoding a nuclease specifically expressed in the female germline. Dev. Biol. 178, 90–100 (1996).

    Article  CAS  PubMed  Google Scholar 

  104. Yoo, S. & McKee, B. D. Functional analysis of the Drosophila Rad51 gene (spn-A) in repair of DNA damage and meiotic chromosome segregation. DNA Repair 4, 231–242 (2005).

    Article  CAS  PubMed  Google Scholar 

  105. Blanton, H. & Sekelsky, J. Unique invasions and resolutions: DNA repair proteins in meiotic recombination in Drosophila melanogaster. Cytogenet. Genome Res. 107, 172–179 (2004).

    Article  CAS  PubMed  Google Scholar 

  106. McVey, M., Andersen, S. L., Broze, Y. & Sekelsky, J. Multiple functions of Drosophila BLM helicase in maintenance of genome stability. Genetics 176, 1979–1992 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  107. Carpenter, A. T. & Sandler, L. On recombination-defective meiotic mutants in Drosophila melanogaster. Genetics 76, 453–475 (1974).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  108. Grell, R. F. Time of recombination in the Drosophila melanogaster oocyte. III. selection and characterization of temperature-sensitive and -insensitive, recombination-deficient alleles in Drosophila. Genetics 108, 425–443 (1984).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  109. Baker, B. S. & Carpenter, A. T. Genetic analysis of sex chromosomal meiotic mutants in Drosophilia melanogaster. Genetics 71, 255–286 (1972).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  110. Blanton, H. L. et al. REC, Drosophila MCM8, drives formation of meiotic crossovers. PLoS Genet. 1, e40 (2005).

    Article  PubMed Central  PubMed  Google Scholar 

  111. Page, S. L. et al. A germline clone screen for meiotic mutants in Drosophila melanogaster. Fly 1, 172–181 (2007).

    Article  PubMed  Google Scholar 

  112. Lake, C. M., Teeter, K., Page, S. L., Nielsen, R. & Hawley, R. S. A genetic analysis of the Drosophila mcm5 gene defines a domain specifically required for meiotic recombination. Genetics 176, 2151–2163 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  113. Kohl, K. P., Jones, C. D. & Sekelsky, J. Evolution of an MCM complex in flies that promotes meiotic crossovers by blocking BLM helicase. Science 338, 1363–1365 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  114. Green, M. M. mus(3)312D1, a mutagen sensitive mutant with profound effects on female meiosis in Drosophila melanogaster. Chromosoma 82, 259–266 (1981).

    Article  CAS  PubMed  Google Scholar 

  115. Radford, S. J., Goley, E., Baxter, K., McMahan, S. & Sekelsky, J. Drosophila ERCC1 is required for a subset of MEI-9-dependent meiotic crossovers. Genetics 170, 1737–1745 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  116. Joyce, E. F., Tanneti, S. N. & McKim, K. S. Drosophila hold’em is required for a subset of meiotic crossovers and interacts with the dna repair endonuclease complex subunits MEI-9 and ERCC1. Genetics 181, 335–340 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  117. Trowbridge, K., McKim, K., Brill, S. J. & Sekelsky, J. Synthetic lethality of Drosophila in the absence of the MUS81 endonuclease and the DmBlm helicase is associated with elevated apoptosis. Genetics 176, 1993–2001 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  118. Dernburg, A. F. et al. Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis. Cell 94, 387–398 (1998).

    Article  CAS  PubMed  Google Scholar 

  119. Hinman, A. W. et al. Caenorhabditis elegans DSB-3 reveals conservation and divergence among protein complexes promoting meiotic double-strand breaks. Proc. Natl Acad. Sci. USA 118, e2109306118 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  120. Stamper, E. L. et al. Identification of DSB-1, a protein required for initiation of meiotic recombination in Caenorhabditis elegans, illuminates a crossover assurance checkpoint. PLoS Genet. 9, e1003679 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  121. Rosu, S. et al. The C. elegans DSB-2 protein reveals a regulatory network that controls competence for meiotic DSB formation and promotes crossover assurance. PLoS Genet. 9, e1003674 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  122. Zetka, M. C., Kawasaki, I., Strome, S. & Muller, F. Synapsis and chiasma formation in Caenorhabditis elegans require HIM-3, a meiotic chromosome core component that functions in chromosome segregation. Genes Dev. 13, 2258–2270 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  123. Kim, Y. et al. The chromosome axis controls meiotic events through a hierarchical assembly of HORMA domain proteins. Dev. Cell 31, 487–502 (2014).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  124. Couteau, F. & Zetka, M. HTP-1 coordinates synaptonemal complex assembly with homolog alignment during meiosis in C. elegans. Genes Dev. 19, 2744–2756 (2005).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  125. Fukuda, T., Daniel, K., Wojtasz, L., Toth, A. & Hoog, C. A novel mammalian HORMA domain-containing protein, HORMAD1, preferentially associates with unsynapsed meiotic chromosomes. Exp. Cell Res. 316, 158–171 (2010).

    Article  CAS  PubMed  Google Scholar 

  126. Shin, Y. H. et al. Hormad1 mutation disrupts synaptonemal complex formation, recombination, and chromosome segregation in mammalian meiosis. PLoS Genet. 6, e1001190 (2010).

    Article  PubMed Central  PubMed  Google Scholar 

  127. Hollingsworth, N. M. & Byers, B. HOP1: a yeast meiotic pairing gene. Genetics 121, 445–462 (1989).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  128. Caryl, A. P., Armstrong, S. J., Jones, G. H. & Franklin, F. C. A homologue of the yeast HOP1 gene is inactivated in the Arabidopsis meiotic mutant asy1. Chromosoma 109, 62–71 (2000).

    Article  CAS  PubMed  Google Scholar 

  129. Latypov, V. et al. Roles of Hop1 and Mek1 in meiotic chromosome pairing and recombination partner choice in Schizosaccharomyces pombe. Mol. Cell Biol. 30, 1570–1581 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  130. Hayashi, M., Chin, G. M. & Villeneuve, A. M. C. elegans germ cells switch between distinct modes of double-strand break repair during meiotic prophase progression. PLoS Genet. 3, e191 (2007).

    Article  PubMed Central  PubMed  Google Scholar 

  131. Girard, C., Roelens, B., Zawadzki, K. A. & Villeneuve, A. M. Interdependent and separable functions of Caenorhabditis elegans MRN-C complex members couple formation and repair of meiotic DSBs. Proc. Natl Acad. Sci. USA 115, E4443–E4452 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  132. Penkner, A. et al. A conserved function for a Caenorhabditis elegans Com1/Sae2/CtIP protein homolog in meiotic recombination. EMBO J. 26, 5071–5082 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  133. Alpi, A., Pasierbek, P., Gartner, A. & Loidl, J. Genetic and cytological characterization of the recombination protein RAD-51 in Caenorhabditis elegans. Chromosoma 112, 6–16 (2003).

    Article  CAS  PubMed  Google Scholar 

  134. Rinaldo, C., Bazzicalupo, P., Ederle, S., Hilliard, M. & La Volpe, A. Roles for Caenorhabditis elegans rad-51 in meiosis and in resistance to ionizing radiation during development. Genetics 160, 471–479 (2002).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  135. Youds, J. L. et al. RTEL-1 enforces meiotic crossover interference and homeostasis. Science 327, 1254–1258 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  136. Zhang, L., Kohler, S., Rillo-Bohn, R. & Dernburg, A. F. A compartmentalized signaling network mediates crossover control in meiosis. eLife 7, e30789 (2018).

    Article  PubMed Central  PubMed  Google Scholar 

  137. Nguyen, H., Labella, S., Silva, N., Jantsch, V. & Zetka, M. C. elegans ZHP-4 is required at multiple distinct steps in the formation of crossovers and their transition to segregation competent chiasmata. PLoS Genet. 14, e1007776 (2018).

    Article  PubMed Central  PubMed  Google Scholar 

  138. Zalevsky, J., MacQueen, A. J., Duffy, J. B., Kemphues, K. J. & Villeneuve, A. M. Crossing over during Caenorhabditis elegans meiosis requires a conserved MutS-based pathway that is partially dispensable in budding yeast. Genetics 153, 1271–1283 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  139. Yokoo, R. et al. COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers. Cell 149, 75–87 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  140. Agostinho, A. et al. Combinatorial regulation of meiotic holliday junction resolution in C. elegans by HIM-6 (BLM) helicase, SLX-4, and the SLX-1, MUS-81 and XPF-1 nucleases. PLoS Genet. 9, e1003591 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  141. O’Neil, N. J. et al. Joint molecule resolution requires the redundant activities of MUS-81 and XPF-1 during Caenorhabditis elegans meiosis. PLoS Genet. 9, e1003582 (2013).

    Article  PubMed Central  PubMed  Google Scholar 

  142. Saito, T. T., Lui, D. Y., Kim, H. M., Meyer, K. & Colaiacovo, M. P. Interplay between structure-specific endonucleases for crossover control during Caenorhabditis elegans meiosis. PLoS Genet. 9, e1003586 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  143. Wicky, C. et al. Multiple genetic pathways involving the Caenorhabditis elegans Bloom’s syndrome genes him-6, rad-51, and top-3 are needed to maintain genome stability in the germ line. Mol. Cell Biol. 24, 5016–5027 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  144. Romanienko, P. J. & Camerini-Otero, R. D. The mouse Spo11 gene is required for meiotic chromosome synapsis. Mol. Cell 6, 975–987 (2000).

    Article  CAS  PubMed  Google Scholar 

  145. Baudat, F., Manova, K., Yuen, J. P., Jasin, M. & Keeney, S. Chromosome synapsis defects and sexually dimorphic meiotic progression in mice lacking Spo11. Mol. Cell 6, 989–998 (2000).

    Article  CAS  PubMed  Google Scholar 

  146. Stanzione, M. et al. Meiotic DNA break formation requires the unsynapsed chromosome axis-binding protein IHO1 (CCDC36) in mice. Nat. Cell Biol. 18, 1208–1220 (2016).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  147. Kumar, R., Bourbon, H. M. & de Massy, B. Functional conservation of Mei4 for meiotic DNA double-strand break formation from yeasts to mice. Genes Dev. 24, 1266–1280 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  148. Libby, B. J., Reinholdt, L. G. & Schimenti, J. C. Positional cloning and characterization of Mei1, a vertebrate-specific gene required for normal meiotic chromosome synapsis in mice. Proc. Natl Acad. Sci. USA 100, 15706–15711 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  149. Cherry, S. M. et al. The Mre11 complex influences DNA repair, synapsis, and crossing over in murine meiosis. Curr. Biol. 17, 373–378 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  150. Zhang, B., Tang, Z., Li, L. & Lu, L. Y. NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis. Cell Death Differ. 27, 2176–2190 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  151. Yamada, S. et al. Molecular structures and mechanisms of DNA break processing in mouse meiosis. Genes Dev. 34, 806–818 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  152. Paiano, J. et al. ATM and PRDM9 regulate SPO11-bound recombination intermediates during meiosis. Nat. Commun. 11, 857 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  153. Dai, J., Voloshin, O., Potapova, S. & Camerini-Otero, R. D. Meiotic knockdown and complementation reveals essential role of RAD51 in mouse spermatogenesis. Cell Rep. 18, 1383–1394 (2017).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  154. Pittman, D. L. et al. Meiotic prophase arrest with failure of chromosome synapsis in mice deficient for Dmc1, a germline-specific RecA homolog. Mol. Cell 1, 697–705 (1998).

    Article  CAS  PubMed  Google Scholar 

  155. Yoshida, K. et al. The mouse RecA-like gene Dmc1 is required for homologous chromosome synapsis during meiosis. Mol. Cell 1, 707–718 (1998).

    Article  CAS  PubMed  Google Scholar 

  156. La Salle, S. et al. Spata22, a novel vertebrate-specific gene, is required for meiotic progress in mouse germ cells. Biol. Reprod. 86, 45 (2012).

    Article  PubMed  Google Scholar 

  157. Luo, M. et al. MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination. Nat. Commun. 4, 2788 (2013).

    Article  PubMed  Google Scholar 

  158. Souquet, B. et al. MEIOB targets single-strand DNA and is necessary for meiotic recombination. PLoS Genet. 9, e1003784 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  159. Holloway, J. K., Morelli, M. A., Borst, P. L. & Cohen, P. E. Mammalian BLM helicase is critical for integrating multiple pathways of meiotic recombination. J. Cell Biol. 188, 779–789 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  160. de Vries, S. S. et al. Mouse MutS-like protein Msh5 is required for proper chromosome synapsis in male and female meiosis. Genes Dev. 13, 523–531 (1999).

    Article  PubMed Central  PubMed  Google Scholar 

  161. Kneitz, B. et al. MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes Dev. 14, 1085–1097 (2000).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  162. Guiraldelli, M. F., Eyster, C., Wilkerson, J. L., Dresser, M. E. & Pezza, R. J. Mouse HFM1/Mer3 is required for crossover formation and complete synapsis of homologous chromosomes during meiosis. PLoS Genet. 9, e1003383 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  163. Lipkin, S. M. et al. Meiotic arrest and aneuploidy in MLH3-deficient mice. Nat. Genet. 31, 385–390 (2002).

    Article  CAS  PubMed  Google Scholar 

  164. Edelmann, W. et al. Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nat. Genet. 21, 123–127 (1999).

    Article  CAS  PubMed  Google Scholar 

  165. Baker, S. M. et al. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat. Genet. 13, 336–342 (1996).

    Article  CAS  PubMed  Google Scholar 

  166. Edelmann, W. et al. Meiotic pachytene arrest in MLH1-deficient mice. Cell 85, 1125–1134 (1996).

    Article  CAS  PubMed  Google Scholar 

  167. Kadri, N. K. et al. Coding and noncoding variants in HFM1, MLH3, MSH4, MSH5, RNF212, and RNF212B affect recombination rate in cattle. Genome Res. 26, 1323–1332 (2016).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  168. Johnston, S. E., Huisman, J. & Pemberton, J. M. A genomic region containing REC8 and RNF212B is associated with individual recombination rate variation in a wild population of red deer (Cervus elaphus). G3 8, 2265–2276 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  169. Johnston, S. E., Berenos, C., Slate, J. & Pemberton, J. M. Conserved genetic architecture underlying individual recombination rate variation in a wild population of soay sheep (Ovis aries). Genetics 203, 583–598 (2016).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  170. Holloway, J. K., Sun, X., Yokoo, R., Villeneuve, A. M. & Cohen, P. E. Mammalian CNTD1 is critical for meiotic crossover maturation and deselection of excess precrossover sites. J. Cell Biol. 205, 633–641 (2014).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  171. Guiraldelli, M. F. et al. SHOC1 is a ERCC4-(HhH)2-like protein, integral to the formation of crossover recombination intermediates during mammalian meiosis. PLoS Genet. 14, e1007381 (2018).

    Article  PubMed Central  PubMed  Google Scholar 

  172. Reynolds, A. et al. RNF212 is a dosage-sensitive regulator of crossing-over during mammalian meiosis. Nat. Genet. 45, 269–278 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  173. Adelman, C. A. & Petrini, J. H. ZIP4H (TEX11) deficiency in the mouse impairs meiotic double strand break repair and the regulation of crossing over. PLoS Genet. 4, e1000042 (2008).

    Article  PubMed Central  PubMed  Google Scholar 

  174. Yang, F. et al. Meiotic failure in male mice lacking an X-linked factor. Genes Dev. 22, 682–691 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  175. Ward, J. O. et al. Mutation in mouse Hei10, an E3 ubiquitin ligase, disrupts meiotic crossing over. PLoS Genet. 3, 1550–1563 (2007).

    Article  CAS  Google Scholar 

  176. Zhang, Q., Ji, S. Y., Busayavalasa, K. & Yu, C. SPO16 binds SHOC1 to promote homologous recombination and crossing-over in meiotic prophase I. Sci. Adv. 5, eaau9780 (2019).

    Article  PubMed Central  PubMed  Google Scholar 

  177. Holloway, J. K., Booth, J., Edelmann, W., McGowan, C. H. & Cohen, P. E. MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis. PLoS Genet. 4, e1000186 (2008).

    Article  PubMed Central  PubMed  Google Scholar 

  178. Grelon, M., Vezon, D., Gendrot, G. & Pelletier, G. AtSPO11-1 is necessary for efficient meiotic recombination in plants. EMBO J. 20, 589–600 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  179. Stacey, N. J. et al. Arabidopsis SPO11-2 functions with SPO11-1 in meiotic recombination. Plant. J. 48, 206–216 (2006).

    Article  CAS  PubMed  Google Scholar 

  180. Hartung, F. & Puchta, H. Molecular characterisation of two paralogous SPO11 homologues in Arabidopsis thaliana. Nucleic Acids Res. 28, 1548–1554 (2000).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  181. Sugimoto-Shirasu, K., Stacey, N. J., Corsar, J., Roberts, K. & McCann, M. C. DNA topoisomerase VI is essential for endoreduplication in Arabidopsis. Curr. Biol. 12, 1782–1786 (2002).

    Article  CAS  PubMed  Google Scholar 

  182. Hartung, F. et al. An archaebacterial topoisomerase homolog not present in other eukaryotes is indispensable for cell proliferation of plants. Curr. Biol. 12, 1787–1791 (2002).

    Article  CAS  PubMed  Google Scholar 

  183. De Muyt, A. et al. AtPRD1 is required for meiotic double strand break formation in Arabidopsis thaliana. EMBO J. 26, 4126–4137 (2007).

    Article  PubMed Central  PubMed  Google Scholar 

  184. De Muyt, A. et al. A high throughput genetic screen identifies new early meiotic recombination functions in Arabidopsis thaliana. PLoS Genet. 5, e1000654 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  185. Zhang, C. et al. The Arabidopsis thaliana DSB formation (AtDFO) gene is required for meiotic double-strand break formation. Plant. J. 72, 271–281 (2012).

    Article  CAS  PubMed  Google Scholar 

  186. Jolivet, S., Vezon, D., Froger, N. & Mercier, R. Non conservation of the meiotic function of the Ski8/Rec103 homolog in Arabidopsis. Genes Cells 11, 615–622 (2006). This study finds that the Ski8 homologue in A. thaliana Rec103 is not required for meiotic DSB formation, highlighting the importance of rigourous functional studies of homologues across model organisms.

    Article  CAS  PubMed  Google Scholar 

  187. Puizina, J., Siroky, J., Mokros, P., Schweizer, D. & Riha, K. Mre11 deficiency in Arabidopsis is associated with chromosomal instability in somatic cells and Spo11-dependent genome fragmentation during meiosis. Plant. Cell 16, 1968–1978 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  188. Gallego, M. E. et al. Disruption of the Arabidopsis RAD50 gene leads to plant sterility and MMS sensitivity. Plant. J. 25, 31–41 (2001).

    Article  CAS  PubMed  Google Scholar 

  189. Bleuyard, J. Y., Gallego, M. E. & White, C. I. Meiotic defects in the Arabidopsis rad50 mutant point to conservation of the MRX complex function in early stages of meiotic recombination. Chromosoma 113, 197–203 (2004).

    Article  CAS  PubMed  Google Scholar 

  190. Waterworth, W. M. et al. NBS1 is involved in DNA repair and plays a synergistic role with ATM in mediating meiotic homologous recombination in plants. Plant. J. 52, 41–52 (2007).

    Article  CAS  PubMed  Google Scholar 

  191. Uanschou, C. et al. A novel plant gene essential for meiosis is related to the human CtIP and the yeast COM1/SAE2 gene. EMBO J. 26, 5061–5070 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  192. Couteau, F. et al. Random chromosome segregation without meiotic arrest in both male and female meiocytes of a dmc1 mutant of Arabidopsis. Plant. Cell 11, 1623–1634 (1999).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  193. Li, W. et al. The Arabidopsis AtRAD51 gene is dispensable for vegetative development but required for meiosis. Proc. Natl Acad. Sci. USA 101, 10596–10601 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  194. Hartung, F., Suer, S. & Puchta, H. Two closely related RecQ helicases have antagonistic roles in homologous recombination and DNA repair in Arabidopsis thaliana. Proc. Natl Acad. Sci. USA 104, 18836–18841 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  195. Higgins, J. D., Ferdous, M., Osman, K. & Franklin, F. C. The RecQ helicase AtRECQ4A is required to remove inter-chromosomal telomeric connections that arise during meiotic recombination in Arabidopsis. Plant. J. 65, 492–502 (2011).

    Article  CAS  PubMed  Google Scholar 

  196. Hartung, F., Suer, S., Knoll, A., Wurz-Wildersinn, R. & Puchta, H. Topoisomerase 3α and RMI1 suppress somatic crossovers and are essential for resolution of meiotic recombination intermediates in Arabidopsis thaliana. PLoS Genet. 4, e1000285 (2008).

    Article  PubMed Central  PubMed  Google Scholar 

  197. Chelysheva, L., Vezon, D., Belcram, K., Gendrot, G. & Grelon, M. The Arabidopsis BLAP75/Rmi1 homologue plays crucial roles in meiotic double-strand break repair. PLoS Genet. 4, e1000309 (2008).

    Article  PubMed Central  PubMed  Google Scholar 

  198. Crismani, W. et al. FANCM limits meiotic crossovers. Science 336, 1588–1590 (2012).

    Article  CAS  PubMed  Google Scholar 

  199. Chelysheva, L. et al. Zip4/Spo22 is required for class I CO formation but not for synapsis completion in Arabidopsis thaliana. PLoS Genet. 3, e83 (2007).

    Article  PubMed Central  PubMed  Google Scholar 

  200. Macaisne, N. et al. SHOC1, an XPF endonuclease-related protein, is essential for the formation of class I meiotic crossovers. Curr. Biol. 18, 1432–1437 (2008).

    Article  CAS  PubMed  Google Scholar 

  201. Macaisne, N., Vignard, J. & Mercier, R. SHOC1 and PTD form an XPF-ERCC1-like complex that is required for formation of class I crossovers. J. Cell Sci. 124, 2687–2691 (2011).

    Article  CAS  PubMed  Google Scholar 

  202. Lu, P., Wijeratne, A. J., Wang, Z., Copenhaver, G. P. & Ma, H. Arabidopsis PTD is required for type I crossover formation and affects recombination frequency in two different chromosomal regions. J. Genet. Genomics 41, 165–175 (2014).

    Article  CAS  PubMed  Google Scholar 

  203. Wijeratne, A. J., Chen, C., Zhang, W., Timofejeva, L. & Ma, H. The Arabidopsis thaliana PARTING DANCERS gene encoding a novel protein is required for normal meiotic homologous recombination. Mol. Biol. Cell 17, 1331–1343 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  204. Higgins, J. D. et al. AtMSH5 partners AtMSH4 in the class I meiotic crossover pathway in Arabidopsis thaliana, but is not required for synapsis. Plant. J. 55, 28–39 (2008).

    Article  CAS  PubMed  Google Scholar 

  205. Lu, X. et al. The Arabidopsis MutS homolog AtMSH5 is required for normal meiosis. Cell Res. 18, 589–599 (2008).

    Article  CAS  PubMed  Google Scholar 

  206. Higgins, J. D., Armstrong, S. J., Franklin, F. C. & Jones, G. H. The Arabidopsis MutS homolog AtMSH4 functions at an early step in recombination: evidence for two classes of recombination in Arabidopsis. Genes Dev. 18, 2557–2570 (2004).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  207. Chen, C., Zhang, W., Timofejeva, L., Gerardin, Y. & Ma, H. The Arabidopsis ROCK-N-ROLLERS gene encodes a homolog of the yeast ATP-dependent DNA helicase MER3 and is required for normal meiotic crossover formation. Plant. J. 43, 321–334 (2005).

    Article  CAS  PubMed  Google Scholar 

  208. Mercier, R. et al. Two meiotic crossover classes cohabit in Arabidopsis: one is dependent on MER3,whereas the other one is not. Curr. Biol. 15, 692–701 (2005).

    Article  CAS  PubMed  Google Scholar 

  209. Chelysheva, L. et al. The Arabidopsis HEI10 is a new ZMM protein related to Zip3. PLoS Genet. 8, e1002799 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  210. Dion, E., Li, L., Jean, M. & Belzile, F. An Arabidopsis MLH1 mutant exhibits reproductive defects and reveals a dual role for this gene in mitotic recombination. Plant. J. 51, 431–440 (2007).

    Article  CAS  PubMed  Google Scholar 

  211. Jackson, N. et al. Reduced meiotic crossovers and delayed prophase I progression in AtMLH3-deficient Arabidopsis. EMBO J. 25, 1315–1323 (2006).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  212. Berchowitz, L. E., Francis, K. E., Bey, A. L. & Copenhaver, G. P. The role of AtMUS81 in interference-insensitive crossovers in A. thaliana. PLoS Genet. 3, e132 (2007).

    Article  PubMed Central  PubMed  Google Scholar 

  213. Thangavel, G., Hofstatter, P. G., Mercier, R. & Marques, A. Tracing the evolution of the plant meiotic molecular machinery. Plant Reprod. 36, 73–95 (2023).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  214. Tzung, K. W. et al. Genomic evidence for a complete sexual cycle in Candida albicans. Proc. Natl Acad. Sci. USA 98, 3249–3253 (2001).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  215. Bloomfield, G., Paschke, P., Okamoto, M., Stevens, T. J. & Urushihara, H. Triparental inheritance in Dictyostelium. Proc. Natl Acad. Sci. USA 116, 2187–2192 (2019).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  216. Forterre, P. & Gadelle, D. Phylogenomics of DNA topoisomerases: their origin and putative roles in the emergence of modern organisms. Nucleic Acids Res. 37, 679–692 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  217. Corbett, K. D., Benedetti, P. & Berger, J. M. Holoenzyme assembly and ATP-mediated conformational dynamics of topoisomerase VI. Nat. Struct. Mol. Biol. 14, 611–619 (2007).

    Article  CAS  PubMed  Google Scholar 

  218. Brinkmeier, J., Coelho, S., de Massy, B. & Bourbon, H. M. Evolution and diversity of the TopoVI and TopoVI-like subunits with extensive divergence of the TOPOVIBL subunit. Mol. Biol. Evol. 39, msac227 (2022). This study investigates the phylogenetic conservation of TopoVI and TopoVI-like subunits.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  219. Ronceret, A., Doutriaux, M. P., Golubovskaya, I. N. & Pawlowski, W. P. PHS1 regulates meiotic recombination and homologous chromosome pairing by controlling the transport of RAD50 to the nucleus. Proc. Natl Acad. Sci. USA 106, 20121–20126 (2009).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  220. Vrielynck, N. et al. Conservation and divergence of meiotic DNA double strand break forming mechanisms in Arabidopsis thaliana. Nucleic Acids Res. 49, 9821–9835 (2021). This study investigates the roles of different components of the meiotic DSB machinery in A. thaliana with a focus on evolutionary conservation and divergence.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  221. Pawlowski, W. P. et al. Coordination of meiotic recombination, pairing, and synapsis by PHS1. Science 303, 89–92 (2004).

    Article  CAS  PubMed  Google Scholar 

  222. Tesse, S., Storlazzi, A., Kleckner, N., Gargano, S. & Zickler, D. Localization and roles of Ski8p protein in Sordaria meiosis and delineation of three mechanistically distinct steps of meiotic homolog juxtaposition. Proc. Natl Acad. Sci. USA 100, 12865–12870 (2003).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  223. Johnson, A. W. & Kolodner, R. D. Synthetic lethality of sep1 (xrn1) ski2 and sep1 (xrn1) ski3 mutants of Saccharomyces cerevisiae is independent of killer virus and suggests a general role for these genes in translation control. Mol. Cell Biol. 15, 2719–2727 (1995).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  224. Yuan, L. et al. The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol. Cell 5, 73–83 (2000).

    Article  CAS  PubMed  Google Scholar 

  225. Ferdous, M. et al. Inter-homolog crossing-over and synapsis in Arabidopsis meiosis are dependent on the chromosome axis protein AtASY3. PLoS Genet. 8, e1002507 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  226. Lemmens, B. B., Johnson, N. M. & Tijsterman, M. COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining. PLoS Genet. 9, e1003276 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  227. Ribeiro, J., Abby, E., Livera, G. & Martini, E. RPA homologs and ssDNA processing during meiotic recombination. Chromosoma 125, 265–276 (2016).

    Article  CAS  PubMed  Google Scholar 

  228. Cloud, V., Chan, Y. L., Grubb, J., Budke, B. & Bishop, D. K. Rad51 is an accessory factor for Dmc1-mediated joint molecule formation during meiosis. Science 337, 1222–1225 (2012).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  229. Da Ines, O. et al. Meiotic recombination in Arabidopsis is catalysed by DMC1, with RAD51 playing a supporting role. PLoS Genet. 9, e1003787 (2013).

    Article  PubMed Central  PubMed  Google Scholar 

  230. Wang, S. et al. Role of EXO1 nuclease activity in genome maintenance, the immune response and tumor suppression in Exo1D173A mice. Nucleic Acids Res. 50, 8093–8106 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  231. Kulkarni, D. S. et al. PCNA activates the MutLγ endonuclease to promote meiotic crossing over. Nature 586, 623–627 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  232. Gioia, M. et al. Exo1 protects DNA nicks from ligation to promote crossover formation during meiosis. PLoS Biol. 21, e3002085 (2023).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  233. Shannon, M. et al. Characterization of the mouse Xpf DNA repair gene and differential expression during spermatogenesis. Genomics 62, 427–435 (1999).

    Article  CAS  PubMed  Google Scholar 

  234. Kirkpatrick, D. T. Roles of the DNA mismatch repair and nucleotide excision repair proteins during meiosis. Cell Mol. Life Sci. 55, 437–449 (1999).

    Article  CAS  PubMed  Google Scholar 

  235. Mastro, T. L. & Forsburg, S. L. Increased meiotic crossovers and reduced genome stability in absence of Schizosaccharomyces pombe Rad16 (XPF). Genetics 198, 1457–1472 (2014).

    Article  PubMed Central  PubMed  Google Scholar 

  236. Hsia, K. T. et al. DNA repair gene Ercc1 is essential for normal spermatogenesis and oogenesis and for functional integrity of germ cell DNA in the mouse. Development 130, 369–378 (2003).

    Article  CAS  PubMed  Google Scholar 

  237. Meneely, P. M., Farago, A. F. & Kauffman, T. M. Crossover distribution and high interference for both the X chromosome and an autosome during oogenesis and spermatogenesis in Caenorhabditis elegans. Genetics 162, 1169–1177 (2002).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  238. Weinstein, A. The geometry and mechanics of crossing over. Cold Spring Harb. Symp. Quant. Biol. 23, 177–196 (1958).

    Article  CAS  PubMed  Google Scholar 

  239. Crismani, W. et al. MCM8 is required for a pathway of meiotic double-strand break repair independent of DMC1 in Arabidopsis thaliana. PLoS Genet. 9, e1003165 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  240. Rao, H. B. et al. A SUMO-ubiquitin relay recruits proteasomes to chromosome axes to regulate meiotic recombination. Science 355, 403–407 (2017).

    Article  PubMed  Google Scholar 

  241. Swanson, W. J. & Vacquier, V. D. The rapid evolution of reproductive proteins. Nat. Rev. Genet. 3, 137–144 (2002).

    Article  CAS  PubMed  Google Scholar 

  242. Clark, N. L., Aagaard, J. E. & Swanson, W. J. Evolution of reproductive proteins from animals and plants. Reproduction 131, 11–22 (2006).

    Article  CAS  PubMed  Google Scholar 

  243. Civetta, A. & Singh, R. S. High divergence of reproductive tract proteins and their association with postzygotic reproductive isolation in Drosophila melanogaster and Drosophila virilis group species. J. Mol. Evol. 41, 1085–1095 (1995).

    Article  CAS  PubMed  Google Scholar 

  244. Haerty, W. et al. Evolution in the fast lane: rapidly evolving sex-related genes in Drosophila. Genetics 177, 1321–1335 (2007).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  245. Coulthart, M. B. & Singh, R. S. High level of divergence of male-reproductive-tract proteins, between Drosophila melanogaster and its sibling species, D. simulans. Mol. Biol. Evol. 5, 182–191 (1988).

    CAS  PubMed  Google Scholar 

  246. Makalowski, W. & Boguski, M. S. Evolutionary parameters of the transcribed mammalian genome: an analysis of 2,820 orthologous rodent and human sequences. Proc. Natl Acad. Sci. USA 95, 9407–9412 (1998).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  247. Torgerson, D. G., Kulathinal, R. J. & Singh, R. S. Mammalian sperm proteins are rapidly evolving: evidence of positive selection in functionally diverse genes. Mol. Biol. Evol. 19, 1973–1980 (2002).

    Article  CAS  PubMed  Google Scholar 

  248. Turner, L. M., Chuong, E. B. & Hoekstra, H. E. Comparative analysis of testis protein evolution in rodents. Genetics 179, 2075–2089 (2008).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  249. Anderson, J. A., Gilliland, W. D. & Langley, C. H. Molecular population genetics and evolution of Drosophila meiosis genes. Genetics 181, 177–185 (2009).

    Article  PubMed Central  PubMed  Google Scholar 

  250. Brand, C. L., Cattani, M. V., Kingan, S. B., Landeen, E. L. & Presgraves, D. C. Molecular evolution at a meiosis gene mediates species differences in the rate and patterning of recombination. Curr. Biol. 28, 1289–1295 (2018). This study uses phylogenetic and transgenic approaches to show that sequence differences in mei-218 between Drosophila species affect the function of the protein in controlling recombination rates.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  251. Sidhu, G. K., Warzecha, T. & Pawlowski, W. P. Evolution of meiotic recombination genes in maize and teosinte. BMC Genomics 18, 106 (2017).

    Article  PubMed Central  PubMed  Google Scholar 

  252. Dudka, D., Akins, R. B. & Lampson, M. A. FREEDA: An automated computational pipeline guides experimental testing of protein innovation. J. Cell Biol. 222, e202212084 (2023).

    Article  CAS  PubMed  Google Scholar 

  253. Bomblies, K., Higgins, J. D. & Yant, L. Meiosis evolves: adaptation to external and internal environments. N. Phytol. 208, 306–323 (2015).

    Article  CAS  Google Scholar 

  254. Morgan, C. et al. Evolution of crossover interference enables stable autopolyploidy by ensuring pairwise partner connections in Arabidopsis arenosa. Curr. Biol. 31, 4713–4726 (2021). This study shows how increased strength of crossover interference can promote successful meiosis in new autotetraploid A. arenosa.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  255. Morgan, C., Zhang, H., Henry, C. E., Franklin, F. C. H. & Bomblies, K. Derived alleles of two axis proteins affect meiotic traits in autotetraploid Arabidopsis arenosa. Proc. Natl Acad. Sci. USA 117, 8980–8988 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  256. Melters, D. P., Paliulis, L. V., Korf, I. F. & Chan, S. W. Holocentric chromosomes: convergent evolution, meiotic adaptations, and genomic analysis. Chromosome Res. 20, 579–593 (2012).

    Article  CAS  PubMed  Google Scholar 

  257. Schvarzstein, M., Wignall, S. M. & Villeneuve, A. M. Coordinating cohesion, co-orientation, and congression during meiosis: lessons from holocentric chromosomes. Genes Dev. 24, 219–228 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  258. Barnes, T. M., Kohara, Y., Coulson, A. & Hekimi, S. Meiotic recombination, noncoding DNA and genomic organization in Caenorhabditis elegans. Genetics 141, 159–179 (1995).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  259. Albertson, D. G., Rose, A. M. & Villeneuve, A. M. in C. elegans II. 2nd edn (eds Riddle, D. L. et al.) Ch. 3 (Cold Spring Harbor Laboratory Press, 1997).

  260. Albertson, D. G. & Thomson, J. N. Segregation of holocentric chromosomes at meiosis in the nematode, Caenorhabditis elegans. Chromosome Res 1, 15–26 (1993).

    Article  CAS  PubMed  Google Scholar 

  261. Pan, J. et al. A hierarchical combination of factors shapes the genome-wide topography of yeast meiotic recombination initiation. Cell 144, 719–731 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  262. Kaback, D. B., Guacci, V., Barber, D. & Mahon, J. W. Chromosome size-dependent control of meiotic recombination. Science 256, 228–232 (1992).

    Article  CAS  PubMed  Google Scholar 

  263. Murakami, H. et al. Multilayered mechanisms ensure that short chromosomes recombine in meiosis. Nature 582, 124–128 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  264. Acquaviva, L. et al. Ensuring meiotic DNA break formation in the mouse pseudoautosomal region. Nature 582, 426–431 (2020). This study describes how mouse sex chromosomes use a specialized mechanism to ensure recombination in the PAR and how a rapidly evolving protein, ANKRD31, is required.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  265. Kauppi, L. et al. Distinct properties of the XY pseudoautosomal region crucial for male meiosis. Science 331, 916–920 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  266. Soriano, P. et al. High rate of recombination and double crossovers in the mouse pseudoautosomal region during male meiosis. Proc. Natl Acad. Sci. USA 84, 7218–7220 (1987).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  267. Blackmon, H. & Demuth, J. P. The fragile Y hypothesis: Y chromosome aneuploidy as a selective pressure in sex chromosome and meiotic mechanism evolution. Bioessays 37, 942–950 (2015).

    Article  CAS  PubMed  Google Scholar 

  268. Ruiz-Herrera, A. & Waters, P. D. Fragile, unfaithful and persistent Ys — on how meiosis can shape sex chromosome evolution. Heredity 129, 22–30 (2022).

    Article  PubMed Central  PubMed  Google Scholar 

  269. Papanikos, F. et al. Mouse ANKRD31 regulates spatiotemporal patterning of meiotic recombination initiation and ensures recombination between X and Y sex chromosomes. Mol. Cell 74, 1069–1085 (2019).

    Article  CAS  PubMed  Google Scholar 

  270. de la Fuente, R. et al. Meiotic pairing and segregation of achiasmate sex chromosomes in eutherian mammals: the role of SYCP3 protein. PLoS Genet. 3, e198 (2007).

    Article  PubMed Central  PubMed  Google Scholar 

  271. Marin-Gual, L. et al. Strategies for meiotic sex chromosome dynamics and telomeric elongation in marsupials. PLoS Genet. 18, e1010040 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  272. Haig, D. Games in tetrads: segregation, recombination, and meiotic drive. Am. Nat. 176, 404–413 (2010).

    Article  PubMed  Google Scholar 

  273. Werren, J. H. Selfish genetic elements, genetic conflict, and evolutionary innovation. Proc. Natl Acad. Sci. USA 108, 10863–10870 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  274. Navarro-Dominguez, B. et al. Epistatic selection on a selfish segregation distorter supergene - drive, recombination, and genetic load. eLife 11, e78981 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  275. Harvey, A. M. et al. A critical component of meiotic drive in Neurospora is located near a chromosome rearrangement. Genetics 197, 1165–1174 (2014).

    Article  PubMed Central  PubMed  Google Scholar 

  276. Hu, W. et al. A large gene family in fission yeast encodes spore killers that subvert Mendel’s law. eLife 6, e26057 (2017).

    Article  PubMed Central  PubMed  Google Scholar 

  277. Bravo Nunez, M. A., Sabbarini, I. M., Eide, L. E., Unckless, R. L. & Zanders, S. E. Atypical meiosis can be adaptive in outcrossed Schizosaccharomyces pombe due to wtf meiotic drivers. eLife 9, e57936 (2020). This study shows how increased levels of aneuploidy can be adaptive in the presence of a meiotic driver.

    Article  PubMed Central  PubMed  Google Scholar 

  278. De Carvalho, M. et al. The wtf meiotic driver gene family has unexpectedly persisted for over 100 million years. eLife 11, e81149 (2022).

    Article  PubMed Central  PubMed  Google Scholar 

  279. Lloyd, A., Morgan, C., FC, H. F. & Bomblies, K. Plasticity of meiotic recombination rates in response to temperature in Arabidopsis. Genetics 208, 1409–1420 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  280. Kumar, S. et al. Timetree 5: an expanded resource for species divergence times. Mol. Biol. Evol. 39, msac174 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  281. Lambing, C. et al. Differentiated function and localisation of SPO11-1 and PRD3 on the chromosome axis during meiotic DSB formation in Arabidopsis thaliana. PLoS Genet. 18, e1010298 (2022).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  282. Zhang, Y. et al. Genetic interactions of histone modification machinery Set1 and PAF1C with the recombination complex Rec114-Mer2-Mei4 in the formation of meiotic DNA double-strand breaks. Int. J. Mol. Sci. 21, 2679 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  283. Sun, W., Lorenz, A., Osman, F. & Whitby, M. C. A failure of meiotic chromosome segregation in a fbh1Delta mutant correlates with persistent Rad51–DNA associations. Nucleic Acids Res. 39, 1718–1731 (2011).

    Article  CAS  PubMed  Google Scholar 

  284. Joyce, E. F. et al. Drosophila ATM and ATR have distinct activities in the regulation of meiotic DNA damage and repair. J. Cell Biol. 195, 359–367 (2011).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  285. Li, Q., Hariri, S. & Engebrecht, J. Meiotic double-strand break processing and crossover patterning are regulated in a sex-specific manner by BRCA1-BARD1 in Caenorhabditis elegans. Genetics 216, 359–379 (2020).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  286. Tamura, K., Stecher, G. & Kumar, S. MEGA11: molecular evolutionary genetics analysis version 11. Mol. Biol. Evol. 38, 3022–3027 (2021).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  287. Hong, S. et al. The logic and mechanism of homologous recombination partner choice. Mol. Cell 51, 440–453 (2013).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  288. Kim, K. P. et al. Sister cohesion and structural axis components mediate homolog bias of meiotic recombination. Cell 143, 924–937 (2010).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  289. McMahill, M. S., Sham, C. W. & Bishop, D. K. Synthesis-dependent strand annealing in meiosis. PLoS Biol. 5, e299 (2007).

    Article  PubMed Central  PubMed  Google Scholar 

  290. Allers, T. & Lichten, M. Intermediates of yeast meiotic recombination contain heteroduplex DNA. Mol. Cell 8, 225–231 (2001).

    Article  CAS  PubMed  Google Scholar 

  291. Hunter, N. & Kleckner, N. The single-end invasion: an asymmetric intermediate at the double-strand break to double-holliday junction transition of meiotic recombination. Cell 106, 59–70 (2001).

    Article  CAS  PubMed  Google Scholar 

  292. Schwacha, A. & Kleckner, N. Identification of double Holliday junctions as intermediates in meiotic recombination. Cell 83, 783–791 (1995).

    Article  CAS  PubMed  Google Scholar 

  293. Paigen, K. & Petkov, P. M. PRDM9 and its role in genetic recombination. Trends Genet. 34, 291–300 (2018).

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  294. Grey, C., Baudat, F. & de Massy, B. PRDM9, a driver of the genetic map. PLoS Genet. 14, e1007479 (2018).

    Article  PubMed Central  PubMed  Google Scholar 

  295. Gregorova, S. et al. Modulation of Prdm9-controlled meiotic chromosome asynapsis overrides hybrid sterility in mice. eLife 7, e34282 (2018).

    Article  PubMed Central  PubMed  Google Scholar 

  296. Baker, Z., Przeworski, M. & Sella, G. Down the Penrose stairs, or how selection for fewer recombination hotspots maintains their existence. eLife 12, e83769 (2023).

    Article  PubMed  Google Scholar 

  297. Davies, B. et al. Re-engineering the zinc fingers of PRDM9 reverses hybrid sterility in mice. Nature 530, 171–176 (2016). This study shows that a humanized PRDM9 allele can rescue hybrid sterility in mice by re-directing meiotic DSB hot spots.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  298. Zelkowski, M., Olson, M. A., Wang, M. & Pawlowski, W. Diversity and determinants of meiotic recombination landscapes. Trends Genet. 35, 359–370 (2019).

    Article  CAS  PubMed  Google Scholar 

  299. Henderson, I. R. & Bomblies, K. Evolution and plasticity of genome-wide meiotic recombination rates. Annu. Rev. Genet. 55, 23–43 (2021). This review covers the literature that describes the variation of meiotic recombination rates.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors apologize to authors whose work could not be cited owing to space limitations. They thank M. Marcet-Ortega for the micrograph of the mouse spermatocyte spread in Fig. 1b. M.A. was supported by an EMBO long-term fellowship (ALTF 905-2019) and a postdoctoral award from the SKI Basic Research Innovation Award Initiative and the Dewitt Wallace Basic Science Award Fund. Research in the Keeney lab is supported in part by National Cancer Institute Cancer Center support grant P30 CA08748, NIH grants R35 GM118092 (to S.K.) and R01 HD110120 (to S.K. and D. Patel) and the Howard Hughes Medical Institute.

Author information

Authors and Affiliations

Authors

Contributions

The authors contributed equally to all aspects of the article.

Corresponding author

Correspondence to Scott Keeney.

Ethics declarations

Competing interests

The authors declare no competing interests.

Peer review

Peer review information:

Nature Reviews Genetics thanks Ian Henderson and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Aneuploidy

Describes the occurrence of missing or extra chromosomes (or parts of chromosomes) in a cell. Meiotic errors that lead to aneuploidy in gametes can have detrimental consequences for an organism.

Crossover

One potential product of the homologous recombination DNA repair pathway. During a crossover event, the DNA flanking the break site is reciprocally exchanged.

Crossover interference

Describes the observation that crossovers show a non-random distribution along chromosomes in which presence of a crossover is accompanied by a reduced likelihood of finding another crossover nearby. As a consequence of interference, crossovers tend to be widely and evenly spaced.

DNA double-strand breaks

DNA lesions in which both DNA strands are cut. During meiosis, DNA double-strand breaks are essential to initiate homologous recombination.

Haploidization

The reduction of the genome complement by half. Haploidization is essential during meiosis to allow the restoration of the genome content at fertilization.

Homologous chromosomes

Homologous chromosomes (homologues) in diploid organisms are pairs of chromosomes that contain the same genes but are of different parental origin. During meiosis, homologous chromosomes are paired to achieve segregation.

Meiotic drivers

Genetic loci that gain a transmission advantage, not by conferring a fitness advantage, but instead by promoting their inheritance in more than 50% of gametes through manipulation of the meiotic process.

Molecular evolution

The study of evolutionary changes at the DNA level. The molecular evolution approaches discussed in this Review aim to distinguish whether protein-coding genes or gene domains experience purifying or positive selection.

Non-crossover

A product of homologous recombination in which no reciprocal exchange of chromosome arms happens, and exchange of genetic information (usually non-reciprocal) is limited.

Positive selection

Describes a process in which novel genetic variants confer a fitness advantage and thus become fixed in a population. This is in contrast to genetic variants that are neutral and become fixed owing to genetic drift.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arter, M., Keeney, S. Divergence and conservation of the meiotic recombination machinery. Nat Rev Genet (2023). https://doi.org/10.1038/s41576-023-00669-8

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41576-023-00669-8

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing