Skip to main content

Thank you for visiting 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.

From molecules to populations: appreciating and estimating recombination rate variation


Recombination is a central biological process with implications for many areas in the life sciences. Yet we are only beginning to appreciate variation in the recombination rate along the genome and among individuals, populations and species. Spurred by technological advances, we are now able to bring variation in this key biological parameter to centre stage. Here, we review the conceptual implications of recombination rate variation and guide the reader through the assumptions, strengths and weaknesses of genomic inference methods, including population-based, pedigree-based and gamete-based approaches. Appreciation of the differences and commonalities of these approaches is a prerequisite to formulate a unifying and comparative framework for understanding the molecular and evolutionary mechanisms shaping, and being shaped by, recombination.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Recombination variation.
Fig. 2: Mapping functions.
Fig. 3: Single-gamete versus bulk-gamete sequencing.
Fig. 4: From inference to landscape.


  1. 1.

    Cavalier-Smith, T. Origins of the machinery of recombination and sex. Heredity 88, 125–141 (2002).

    CAS  PubMed  Google Scholar 

  2. 2.

    Ortiz-Barrientos, D., Engelstädter, J. & Rieseberg, L. H. Recombination rate evolution and the origin of species. Trends Ecol. Evol. 31, 226–236 (2016).

    PubMed  Google Scholar 

  3. 3.

    Hansen, T. F. The evolution of genetic architecture. Annu. Rev. Ecol. Evol. Syst. 37, 123–157 (2006).

    Google Scholar 

  4. 4.

    Cooper, T. F. Recombination speeds adaptation by reducing competition between beneficial mutations in populations of Escherichia coli. PLoS Biol. 5, e225 (2007).

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Butlin, R. K. Recombination and speciation. Mol. Ecol. 14, 2621–2635 (2005). This influential perspective article discusses the variation in recombination, theoretical expectations and its importance for speciation.

    CAS  PubMed  Google Scholar 

  6. 6.

    Otto, S. P. & Lenormand, T. Evolution of sex: resolving the paradox of sex and recombination. Nat. Rev. Genet. 3, 252 (2002).

    CAS  PubMed  Google Scholar 

  7. 7.

    Kaniecki, K., De Tullio, L. & Greene, E. C. A change of view: homologous recombination at single-molecule resolution. Nat. Rev. Genet. 19, 191–207 (2017).

    PubMed  PubMed Central  Google Scholar 

  8. 8.

    Cromie, G. A., Connelly, J. C. & Leach, D. R. Recombination at double-strand breaks and DNA ends: conserved mechanisms from phage to humans. Mol. Cell 8, 1163–1174 (2001).

    CAS  PubMed  Google Scholar 

  9. 9.

    Stapley, J., Feulner, P. G. D., Johnston, S. E., Santure, A. W. & Smadja, C. M. Recombination: the good, the bad and the variable. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20170279 (2017).

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Ritz, K. R., Noor, M. A. F. & Singh, N. D. Variation in recombination rate: adaptive or not? Trends Genet. 33, 364–374 (2017). This review emphasizes population-level variation in recombination rates and discusses the potential molecular constraints and evolutionary processes underlying this variation.

    CAS  PubMed  Google Scholar 

  11. 11.

    Clark, A. G., Wang, X. & Matise, T. Contrasting methods of quantifying fine structure of human recombination. Annu. Rev. Genomics Hum. Genet. 11, 45–64 (2010). This review compares the different recombination inference methods (linkage disequilibrium-based, pedigree-based, sperm-typing and hotspot detection) in humans where the most extensive data are available.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Felsenstein, J. The evolutionary advantage of recombination. Genetics 78, 737–756 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Andolfatto, P. & Przeworski, M. Regions of lower crossing over harbor more rare variants in African populations of Drosophila melanogaster. Genetics 158, 657–665 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Ellegren, H. & Galtier, N. Determinants of genetic diversity. Nat. Rev. Genet. 17, 422–433 (2016).

    CAS  PubMed  Google Scholar 

  15. 15.

    Comeron, J. M. Background selection as null hypothesis in population genomics: insights and challenges from Drosophila studies. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20160471 (2017).

    PubMed  PubMed Central  Google Scholar 

  16. 16.

    Lindholm, A. K. et al. The ecology and evolutionary dynamics of meiotic drive. Trends Ecol. Evol. 31, 315–326 (2016).

    PubMed  Google Scholar 

  17. 17.

    Hill, W. G. & Robertson, A. The effect of linkage on limits to artificial selection. Genet. Res. 8, 269–294 (1966). This article presents the theory describing the behaviour of two linked loci under selection.

    CAS  PubMed  Google Scholar 

  18. 18.

    Gossmann, T. I., Santure, A. W., Sheldon, B. C., Slate, J. & Zeng, K. Highly variable recombinational landscape modulates efficacy of natural selection in birds. Genome Biol. Evol. 6, 2061–2075 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Barton, N. H. A general model for the evolution of recombination. Genet. Res. 65, 123–145 (1995). This article describes mathematical models of how recombination evolves via selection on recombination modifiers.

    CAS  PubMed  Google Scholar 

  20. 20.

    Rice, W. R. Evolution of sex: experimental tests of the adaptive significance of sexual recombination. Nat. Rev. Genet. 3, 241 (2002).

    CAS  PubMed  Google Scholar 

  21. 21.

    Charlesworth, B. Recombination modification in a fluctuating environment. Genetics 83, 181–195 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Charlesworth, B. & Barton, N. H. Recombination load associated with selection for increased recombination. Genet. Res. 67, 27–41 (1996).

    CAS  PubMed  Google Scholar 

  23. 23.

    Rattray, A., Santoyo, G., Shafer, B. & Strathern, J. N. Elevated mutation rate during meiosis in Saccharomyces cerevisiae. PLoS Genet. 11, e1004910 (2015).

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Bolívar, P. et al. Biased inference of selection due to GC-biased gene conversion and the rate of protein evolution in flycatchers when accounting for it. Mol. Biol. Evol. 35, 2475–2486 (2018).

    PubMed  PubMed Central  Google Scholar 

  25. 25.

    Duret, L. & Galtier, N. Biased gene conversion and the evolution of mammalian genomic landscapes. Annu. Rev. Genomics Hum. Genet. 10, 285–311 (2009).

    CAS  PubMed  Google Scholar 

  26. 26.

    Schumer, M. et al. Natural selection interacts with recombination to shape the evolution of hybrid genomes. Science 360, 656–660 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Martin, S. H., Davey, J. W., Salazar, C. & Jiggins, C. D. Recombination rate variation shapes barriers to introgression across butterfly genomes. PLoS Biol. 17, e2006288 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Barton, N. & Bengtsson, B. O. The barrier to genetic exchange between hybridising populations. Heredity 57, 357–376 (1986).

    PubMed  Google Scholar 

  29. 29.

    Nachman, M. W. & Payseur, B. A. Recombination rate variation and speciation: theoretical predictions and empirical results from rabbits and mice. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367, 409–421 (2012).

    PubMed  PubMed Central  Google Scholar 

  30. 30.

    Melamed-Bessudo, C., Shilo, S. & Levy, A. A. Meiotic recombination and genome evolution in plants. Curr. Opin. Plant. Biol. 30, 82–87 (2016).

    CAS  PubMed  Google Scholar 

  31. 31.

    Capilla, L., Garcia Caldés, M. & Ruiz-Herrera, A. Mammalian meiotic recombination: a toolbox for genome evolution. Cytogenet. Genome Res. 150, 1–16 (2016).

    PubMed  Google Scholar 

  32. 32.

    Nam, K. & Ellegren, H. Recombination drives vertebrate genome contraction. PLoS Genet. 8, e1002680 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Corbett-Detig, R. B., Hartl, D. L. & Sackton, T. B. Natural selection constrains neutral diversity across a wide range of species. PLoS Biol. 13, e1002112 (2015).

    PubMed  PubMed Central  Google Scholar 

  34. 34.

    Vandiedonck, C. & Knight, J. C. The human major histocompatibility complex as a paradigm in genomics research. Brief. Funct. Genomic. Proteomic. 8, 379–394 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. 35.

    Charlesworth, B. The evolution of sex chromosomes. Science 251, 1030–1033 (1991).

    CAS  PubMed  Google Scholar 

  36. 36.

    Ellegren, H. Sex-chromosome evolution: recent progress and the influence of male and female heterogamety. Nat. Rev. Genet. 12, 157–166 (2011).

    CAS  PubMed  Google Scholar 

  37. 37.

    Schwander, T., Libbrecht, R. & Keller, L. Supergenes and complex phenotypes. Curr. Biol. 24, R288–R294 (2014).

    CAS  PubMed  Google Scholar 

  38. 38.

    Stapley, J., Feulner, P. G. D., Johnston, S. E., Santure, A. W. & Smadja, C. M. Variation in recombination frequency and distribution across eukaryotes: patterns and processes. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20160455 (2017). This review, part of the special issue ‘Evolutionary Causes and Consequences of Recombination Rate Variation in Sexual Organisms’, includes a meta-analysis characterizing the variation in recombination rates across the tree of life and outlines outstanding questions in the field.

    PubMed  PubMed Central  Google Scholar 

  39. 39.

    Wang, J., Street, N. R., Scofield, D. G. & Ingvarsson, P. K. Natural selection and recombination rate variation shape nucleotide polymorphism across the genomes of three related Populus species. Genetics 202, 1185–1200 (2016).

    CAS  PubMed  Google Scholar 

  40. 40.

    Dumont, B. L. & Payseur, B. A. Evolution of the genomic rate of recombination in mammals. Evolution 62, 276–294 (2008).

    CAS  PubMed  Google Scholar 

  41. 41.

    Dumont, B. L., White, M. A., Steffy, B., Wiltshire, T. & Payseur, B. A. Extensive recombination rate variation in the house mouse species complex inferred from genetic linkage maps. Genome Res. 21, 114–125 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Graffelman, J., Balding, D. J., Gonzalez-Neira, A. & Bertranpetit, J. Variation in estimated recombination rates across human populations. Hum. Genet. 122, 301–310 (2007).

    PubMed  Google Scholar 

  43. 43.

    Thomsen, H. et al. A whole genome scan for differences in recombination rates among three Bos taurus breeds. Mamm. Genome 12, 724–728 (2001).

    CAS  PubMed  Google Scholar 

  44. 44.

    Cheung, V. G., Burdick, J. T., Hirschmann, D. & Morley, M. Polymorphic variation in human meiotic recombination. Am. J. Hum. Genet. 80, 526–530 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Johnston, S. E., Bérénos, 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). This article examines recombination rate variation and isolation of candidate genetic modifier loci in a natural, pedigreed population.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Hussin, J., Roy-Gagnon, M.-H., Gendron, R., Andelfinger, G. & Awadalla, P. Age-dependent recombination rates in human pedigrees. PLoS Genet. 7, e1002251 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Singh, N. D. Wolbachia infection associated with increased recombination in Drosophila. G3 9, 229–237 (2019).

    CAS  PubMed  Google Scholar 

  48. 48.

    Berset-Brändli, L., Jaquiéry, J., Broquet, T., Ulrich, Y. & Perrin, N. Extreme heterochiasmy and nascent sex chromosomes in European tree frogs. Proc. R. Soc. B: Biol. Sci. 275, 1577–1585 (2008).

    Google Scholar 

  49. 49.

    Lenormand, T. & Dutheil, J. Recombination difference between sexes: a role for haploid selection. PLoS Biol. 3, e63 (2005).

    PubMed  PubMed Central  Google Scholar 

  50. 50.

    Haldane, J. B. S. Sex ratio and unisexual sterility in hybrid animals. J. Genet. 12, 101–109 (1922).

    Google Scholar 

  51. 51.

    Huxley, J. S. Sexual difference of linkage in Gammarus chevreuxi. J. Genet. 20, 145–156 (1928).

    Google Scholar 

  52. 52.

    Charlesworth, D. Evolution of recombination rates between sex chromosomes. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20160456 (2017).

    PubMed  PubMed Central  Google Scholar 

  53. 53.

    Bergero, R. & Charlesworth, D. The evolution of restricted recombination in sex chromosomes. Trends Ecol. Evol. 24, 94–102 (2009).

    PubMed  Google Scholar 

  54. 54.

    Limborg, M. T., McKinney, G. J., Seeb, L. W. & Seeb, J. E. Recombination patterns reveal information about centromere location on linkage maps. Mol. Ecol. Resour. 16, 655–661 (2016).

    CAS  PubMed  Google Scholar 

  55. 55.

    Vincenten, N. et al. The kinetochore prevents centromere-proximal crossover recombination during meiosis. eLife 4, e10850 (2015).

    PubMed  PubMed Central  Google Scholar 

  56. 56.

    Haenel, Q., Laurentino, T. G., Roesti, M. & Berner, D. Meta-analysis of chromosome-scale crossover rate variation in eukaryotes and its significance to evolutionary genomics. Mol. Ecol. 27, 2477–2497 (2018).

    PubMed  Google Scholar 

  57. 57.

    Morgan, A. P. et al. Structural variation shapes the landscape of recombination in mouse. Genetics 206, 603–619 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. 58.

    Völker, M. et al. Copy number variation, chromosome rearrangement, and their association with recombination during avian evolution. Genome Res. 20, 503–511 (2010).

    PubMed  PubMed Central  Google Scholar 

  59. 59.

    Fullerton, S. M., Bernardo Carvalho, A. & Clark, A. G. Local rates of recombination are positively correlated with GC content in the human genome. Mol. Biol. Evol. 18, 1139–1142 (2001).

    CAS  PubMed  Google Scholar 

  60. 60.

    Marsolier-Kergoat, M.-C. & Yeramian, E. GC content and recombination: reassessing the causal effects for the Saccharomyces cerevisiae genome. Genetics 183, 31–38 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Freudenberg, J., Wang, M., Yang, Y. & Li, W. Partial correlation analysis indicates causal relationships between GC-content, exon density and recombination rate in the human genome. BMC Bioinforma. 10 (Suppl 1), S66 (2009).

    Google Scholar 

  62. 62.

    Kent, T. V., Uzunović, J. & Wright, S. I. Coevolution between transposable elements and recombination. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20160458 (2017).

    PubMed  PubMed Central  Google Scholar 

  63. 63.

    Rizzon, C., Marais, G., Gouy, M. & Biémont, C. Recombination rate and the distribution of transposable elements in the Drosophila melanogaster genome. Genome Res. 12, 400–407 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. 64.

    Dolgin, E. S. & Charlesworth, B. The effects of recombination rate on the distribution and abundance of transposable elements. Genetics 178, 2169–2177 (2008).

    PubMed  PubMed Central  Google Scholar 

  65. 65.

    Myers, S., Bottolo, L., Freeman, C., McVean, G. & Donnelly, P. A fine-scale map of recombination rates and hotspots across the human genome. Science 310, 321–324 (2005).

    CAS  PubMed  Google Scholar 

  66. 66.

    Paigen, K. & Petkov, P. Mammalian recombination hot spots: properties, control and evolution. Nat. Rev. Genet. 11, 221–233 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. 67.

    Lichten, M. & Goldman, A. S. Meiotic recombination hotspots. Annu. Rev. Genet. 29, 423–444 (1995).

    CAS  PubMed  Google Scholar 

  68. 68.

    Paul, P., Nag, D. & Chakraborty, S. Recombination hotspots: models and tools for detection. DNA Repair 40, 47–56 (2016). This detailed review covers recombination hotspot evolution, molecular mechanisms underlying recombination and comparison of various inference methods of hotspot detection.

    CAS  PubMed  Google Scholar 

  69. 69.

    Arnheim, N., Calabrese, P. & Tiemann-Boege, I. Mammalian meiotic recombination hot spots. Annu. Rev. Genet. 41, 369–399 (2007).

    CAS  PubMed  Google Scholar 

  70. 70.

    Choi, K. & Henderson, I. R. Meiotic recombination hotspots — a comparative view. Plant J. 83, 52–61 (2015).

    CAS  PubMed  Google Scholar 

  71. 71.

    Weng, Z. et al. Identification of recombination hotspots and quantitative trait loci for recombination rate in layer chickens. J. Anim. Sci. Biotechnol. 10, 20 (2019).

    PubMed  PubMed Central  Google Scholar 

  72. 72.

    Kong, A. et al. Fine-scale recombination rate differences between sexes, populations and individuals. Nature 467, 1099–1103 (2010).

    CAS  PubMed  Google Scholar 

  73. 73.

    Hunter, C. M., Huang, W., Mackay, T. F. C. & Singh, N. D. The genetic architecture of natural variation in recombination rate in Drosophila melanogaster. PLoS Genet. 12, e1005951 (2016).

    PubMed  PubMed Central  Google Scholar 

  74. 74.

    Chinnici, J. P. Modification of recombination frequency in Drosophila. I. Selection for increased and decreased crossing over. Genetics 69, 71–83 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. 75.

    Shaw, D. D. Genetic and environmental components of chiasma control. Chromosoma 37, 297–308 (1972).

    CAS  PubMed  Google Scholar 

  76. 76.

    Parsons, P. A. Evolutionary rates: effects of stress upon recombination. Biol. J. Linn. Soc. Lond. 35, 49–68 (1988).

    Google Scholar 

  77. 77.

    Stevison, L. S., Sefick, S., Rushton, C. & Graze, R. M. Recombination rate plasticity: revealing mechanisms by design. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20160459 (2017).

    PubMed  PubMed Central  Google Scholar 

  78. 78.

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

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Neel, J. V. A relation between larval nutrition and the frequency of crossing over in the third chromosome of Drosophila melanogaster. Genetics 26, 506–516 (1941).

    CAS  PubMed  PubMed Central  Google Scholar 

  80. 80.

    Belyaev, D. K. & Borodin, P. M. The influence of stress on variation and its role in evolution. Biol. Zent. Bl. 101, 705–714 (1982).

    Google Scholar 

  81. 81.

    Kong, A. et al. Recombination rate and reproductive success in humans. Nat. Genet. 36, 1203–1206 (2004).

    CAS  PubMed  Google Scholar 

  82. 82.

    Lobkovsky, A. E., Wolf, Y. I. & Koonin, E. V. Evolvability of an optimal recombination rate. Genome Biol. Evol. 8, 70–77 (2015).

    PubMed  PubMed Central  Google Scholar 

  83. 83.

    Alves, I., Houle, A. A., Hussin, J. G. & Awadalla, P. The impact of recombination on human mutation load and disease. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, 20160465 (2017).

    PubMed  PubMed Central  Google Scholar 

  84. 84.

    Székvölgyi, L., Ohta, K. & Nicolas, A. Initiation of meiotic homologous recombination: flexibility, impact of histone modifications, and chromatin remodeling. Cold Spring Harb. Perspect. Biol. 7, a016527 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Salathé, M., Kouyos, R. D., Regoes, R. R. & Bonhoeffer, S. Rapid parasite adaptation drives selection for high recombination rates. Evolution 62, 295–300 (2008).

    PubMed  Google Scholar 

  86. 86.

    Lenormand, T. & Otto, S. P. The evolution of recombination in a heterogeneous environment. Genetics 156, 423–438 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. 87.

    Mank, J. E. The evolution of heterochiasmy: the role of sexual selection and sperm competition in determining sex-specific recombination rates in eutherian mammals. Genet. Res. 91, 355–363 (2009).

    CAS  Google Scholar 

  88. 88.

    Brandvain, Y. & Coop, G. Scrambling eggs: meiotic drive and the evolution of female recombination rates. Genetics 190, 709–723 (2012).

    PubMed  PubMed Central  Google Scholar 

  89. 89.

    Zelkowski, M., Olson, M. A., Wang, M. & Pawlowski, W. Diversity and determinants of meiotic recombination landscapes. Trends Genet. 35, 359–370 (2019). This review considers the difference between patterns of DSBs and crossover events along the genome across many organisms and discusses the molecular determinants that govern variation in recombination hotspots and landscapes.

    CAS  PubMed  Google Scholar 

  90. 90.

    Gray, S. & Cohen, P. E. Control of meiotic crossovers: from double-strand break formation to designation. Annu. Rev. Genet. 50, 175–210 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Petkov, P. M., Broman, K. W., Szatkiewicz, J. P. & Paigen, K. Crossover interference underlies sex differences in recombination rates. Trends Genet. 23, 539–542 (2007).

    CAS  PubMed  Google Scholar 

  92. 92.

    Zhang, L., Liang, Z., Hutchinson, J. & Kleckner, N. Crossover patterning by the beam-film model: analysis and implications. PLoS Genet. 10, e1004042 (2014).

    PubMed  PubMed Central  Google Scholar 

  93. 93.

    Kleckner, N. et al. A mechanical basis for chromosome function. Proc. Natl Acad. Sci. USA 101, 12592–12597 (2004).

    CAS  PubMed  Google Scholar 

  94. 94.

    Kirkpatrick, M. How and why chromosome inversions evolve. PLoS Biol. 8, e1000501 (2010).

    PubMed  PubMed Central  Google Scholar 

  95. 95.

    Farré, M., Micheletti, D. & Ruiz-Herrera, A. Recombination rates and genomic shuffling in human and chimpanzee — a new twist in the chromosomal speciation theory. Mol. Biol. Evol. 30, 853–864 (2013).

    PubMed  Google Scholar 

  96. 96.

    Crown, K. N., Miller, D. E., Sekelsky, J. & Hawley, R. S. Local inversion heterozygosity alters recombination throughout the genome. Curr. Biol. 28, 2984–2990.e3 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  97. 97.

    Mirouze, M. et al. Loss of DNA methylation affects the recombination landscape in Arabidopsis. Proc. Natl Acad. Sci. USA 109, 5880–5885 (2012).

    CAS  PubMed  Google Scholar 

  98. 98.

    Brachet, E., Sommermeyer, V. & Borde, V. Interplay between modifications of chromatin and meiotic recombination hotspots. Biol. Cell 104, 51–69 (2012).

    CAS  PubMed  Google Scholar 

  99. 99.

    Marand, A. P. et al. Meiotic crossovers are associated with open chromatin and enriched with Stowaway transposons in potato. Genome Biol. 18, 203 (2017).

    PubMed  PubMed Central  Google Scholar 

  100. 100.

    Qiao, H. et al. Antagonistic roles of ubiquitin ligase HEI10 and SUMO ligase RNF212 regulate meiotic recombination. Nat. Genet. 46, 194–199 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Ziolkowski, P. A. et al. Natural variation and dosage of the HEI10 meiotic E3 ligase control Arabidopsis crossover recombination. Genes Dev. 31, 306–317 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Kong, A. et al. Sequence variants in the RNF212 gene associate with genome-wide recombination rate. Science 319, 1398–1401 (2008).

    CAS  PubMed  Google Scholar 

  103. 103.

    Baudat, F. et al. PRDM9 is a major determinant of meiotic recombination hotspots in humans and mice. Science 327, 836–840 (2010).

    CAS  PubMed  Google Scholar 

  104. 104.

    Parvanov, E. D., Petkov, P. M. & Paigen, K. Prdm9 controls activation of mammalian recombination hotspots. Science 327, 835 (2010).

    CAS  PubMed  Google Scholar 

  105. 105.

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

    CAS  PubMed  PubMed Central  Google Scholar 

  106. 106.

    He, Y. et al. Genomic features shaping the landscape of meiotic double-strand-break hotspots in maize. Proc. Natl Acad. Sci. USA 114, 12231–12236 (2017).

    CAS  PubMed  Google Scholar 

  107. 107.

    Shilo, S., Melamed-Bessudo, C., Dorone, Y., Barkai, N. & Levy, A. A. DNA crossover motifs associated with epigenetic modifications delineate open chromatin regions in Arabidopsis. Plant Cell 27, 2427–2436 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. 108.

    Lange, J. et al. The landscape of mouse meiotic double-strand break formation, processing, and repair. Cell 167, 695–708.e16 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  109. 109.

    Singhal, S. et al. Stable recombination hotspots in birds. Science 350, 928–932 (2015). This article presents a good example of the population-based approach identifying recombination hotpots, their evolutionary stability and the underlying genomic features in avian populations.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Anderson, L. K. et al. High-resolution crossover maps for each bivalent of Zea mays using recombination nodules. Genetics 165, 849–865 (2003). This article is one of the early studies to use MLH1 foci to estimate recombination frequency across the genome.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. 111.

    Rahn, M. I. & Solari, A. J. Recombination nodules in the oocytes of the chicken, Gallus domesticus. Cytogenet. Cell Genet. 43, 187–193 (1986).

    CAS  PubMed  Google Scholar 

  112. 112.

    Pollock, D. L. & Fechheimer, N. S. The chromosomes of cockerels (Gallus domesticus) during meiosis. Cytogenet. Cell Genet. 21, 267–281 (1978).

    CAS  PubMed  Google Scholar 

  113. 113.

    Lawrie, N. M., Tease, C. & Hultén, M. A. Chiasma frequency, distribution and interference maps of mouse autosomes. Chromosoma 104, 308–314 (1995).

    CAS  PubMed  Google Scholar 

  114. 114.

    Herickhoff, L., Stack, S. & Sherman, J. The relationship between synapsis, recombination nodules and chiasmata in tomato translocation heterozygotes. Heredity 71, 373–385 (1993).

    Google Scholar 

  115. 115.

    Holm, P. B. & Rasmussen, S. W. Chromosome pairing, recombination nodules and chiasma formation in diploid Bombyx males. Carlsberg Res. Commun. 45, 483 (1980).

    Google Scholar 

  116. 116.

    Rasmussen, S. W. & Holm, P. B. The synaptonemal complex, recombination nodules and chiasmata in human spermatocytes. Symp. Soc. Exp. Biol. 38, 271–292 (1984).

    CAS  PubMed  Google Scholar 

  117. 117.

    Calderón, P. L. & Pigozzi, M. I. MLH1-focus mapping in birds shows equal recombination between sexes and diversity of crossover patterns. Chromosome Res. 14, 605–612 (2006).

    PubMed  Google Scholar 

  118. 118.

    Sun, F. et al. Variation in MLH1 distribution in recombination maps for individual chromosomes from human males. Hum. Mol. Genet. 15, 2376–2391 (2006).

    CAS  PubMed  Google Scholar 

  119. 119.

    Anderson, L. K., Reeves, A., Webb, L. M. & Ashley, T. Distribution of crossing over on mouse synaptonemal complexes using immunofluorescent localization of MLH1 protein. Genetics 151, 1569–1579 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    del Priore, L. & Pigozzi, M. I. Heterologous synapsis and crossover suppression in heterozygotes for a pericentric inversion in the zebra finch. Cytogenet. Genome Res. 147, 154–160 (2015).

    PubMed  Google Scholar 

  121. 121.

    Zickler, D., Moreau, P. J., Huynh, A. D. & Slezec, A. M. Correlation between pairing initiation sites, recombination nodules and meiotic recombination in Sordaria macrospora. Genetics 132, 135–148 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  122. 122.

    Gruhn, J. R., Rubio, C., Broman, K. W., Hunt, P. A. & Hassold, T. Cytological studies of human meiosis: sex-specific differences in recombination originate at, or prior to, establishment of double-strand breaks. PLoS One 8, e85075 (2013).

    PubMed  PubMed Central  Google Scholar 

  123. 123.

    Golding, G. B. The sampling distribution of linkage disequilibrium. Genetics 108, 257–274 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Pritchard, J. K. & Przeworski, M. Linkage disequilibrium in humans: models and data. Am. J. Hum. Genet. 69, 1–14 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. 125.

    Griffiths, R. C. & Marjoram, P. in Progress in Population Genetics and Human Evolution (eds Donnelly P. & Tavaré S.) 257–270 (Springer, 1997). This article presents a theoretical formalization of the evolutionary history of recombination through the ancestral recombination graph.

  126. 126.

    Arenas, M. The importance and application of the ancestral recombination graph. Front. Genet. 4, 206 (2013).

    PubMed  PubMed Central  Google Scholar 

  127. 127.

    McVean, G., Awadalla, P. & Fearnhead, P. A coalescent-based method for detecting and estimating recombination from gene sequences. Genetics 160, 1231–1241 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. 128.

    Stumpf, M. P. H. & McVean, G. A. T. Estimating recombination rates from population-genetic data. Nat. Rev. Genet. 4, 959–968 (2003). This Review provides details on the models, assumptions and inference methods of the population recombination rate and compares applications in human populations.

    CAS  PubMed  Google Scholar 

  129. 129.

    Hellenthal, G. & Stephens, M. Insights into recombination from population genetic variation. Curr. Opin. Genet. Dev. 16, 565–572 (2006).

    CAS  PubMed  Google Scholar 

  130. 130.

    Hudson, R. R. & Kaplan, N. L. Statistical properties of the number of recombination events in the history of a sample of DNA sequences. Genetics 111, 147–164 (1985).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. 131.

    Myers, S. R. & Griffiths, R. C. Bounds on the minimum number of recombination events in a sample history. Genetics 163, 375–394 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. 132.

    Hudson, R. R. Two-locus sampling distributions and their application. Genetics 159, 1805–1817 (2001). This article presents an influential description of how the population recombination rate can be estimated from data.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. 133.

    Vijay, N. et al. Evolution of heterogeneous genome differentiation across multiple contact zones in a crow species complex. Nat. Commun. 7, 13195 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  134. 134.

    Chan, A. H., Jenkins, P. A. & Song, Y. S. Genome-wide fine-scale recombination rate variation in Drosophila melanogaster. PLoS Genet. 8, e1003090 (2012).

    PubMed  PubMed Central  Google Scholar 

  135. 135.

    Calafell, F., Grigorenko, E. L., Chikanian, A. A. & Kidd, K. K. Haplotype evolution and linkage disequilibrium: a simulation study. Hum. Hered. 51, 85–96 (2001).

    CAS  PubMed  Google Scholar 

  136. 136.

    Wang, N., Akey, J. M., Zhang, K., Chakraborty, R. & Jin, L. Distribution of recombination crossovers and the origin of haplotype blocks: the interplay of population history, recombination, and mutation. Am. J. Hum. Genet. 71, 1227–1234 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  137. 137.

    Barton, N. H. Genetic hitchhiking. Philos. Trans. R. Soc. Lond. B Biol. Sci. 355, 1553–1562 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  138. 138.

    Charlesworth, B., Nordborg, M. & Charlesworth, D. The effects of local selection, balanced polymorphism and background selection on equilibrium patterns of genetic diversity in subdivided populations. Genet. Res. 70, 155–174 (1997).

    CAS  PubMed  Google Scholar 

  139. 139.

    Chapman, N. H. & Thompson, E. A. Linkage disequilibrium mapping: the role of population history, size, and structure. Adv. Genet. 42, 413–437 (2001).

    CAS  PubMed  Google Scholar 

  140. 140.

    Baird, S. J. E. Exploring linkage disequilibrium. Mol. Ecol. Resour. 15, 1017–1019 (2015).

    CAS  PubMed  Google Scholar 

  141. 141.

    Nordborg, M. in Handbook of Statistical Genetics (eds Balding, D. J., Bishop, M. & Cannings, C.) 179–212 (Wiley, 2004).

  142. 142.

    Lander, E. S. & Green, P. Construction of multilocus genetic linkage maps in humans. Proc. Natl Acad. Sci. USA 84, 2363–2367 (1987). This article is the first description of inferring multilocus linkage maps using maximum likelihood in a three-generation human pedigree.

    CAS  PubMed  Google Scholar 

  143. 143.

    Botstein, D., White, R. L., Skolnick, M. & Davis, R. W. Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am. J. Hum. Genet. 32, 314–331 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  144. 144.

    Johnston, S. E., Huisman, J., Ellis, P. A. & Pemberton, J. M. A high-density linkage map reveals sexual dimorphism in recombination landscapes in red deer (Cervus elaphus). G3 7, 2859–2870 (2017).

    CAS  PubMed  Google Scholar 

  145. 145.

    Peñalba, J. V. et al. Genome of an iconic Australian bird: high-quality assembly and linkage map of the superb fairy-wren (Malurus cyaneus). Mol. Ecol. Resour. 20, 560–578 (2020).

    PubMed  Google Scholar 

  146. 146.

    Decker, J. E. et al. Worldwide patterns of ancestry, divergence, and admixture in domesticated cattle. PLoS Genet. 10, e1004254 (2014).

    PubMed  PubMed Central  Google Scholar 

  147. 147.

    Fang, L. et al. Positive correlation between recombination rate and nucleotide diversity is shown under domestication selection in the chicken genome. Chin. Sci. Bull. 53, 746–750 (2008).

    CAS  Google Scholar 

  148. 148.

    Kong, A. et al. A high-resolution recombination map of the human genome. Nat. Genet. 31, 241–247 (2002).

    CAS  PubMed  Google Scholar 

  149. 149.

    Lashermes, P. et al. Genetic linkage map of Coffea canephora: effect of segregation distortion and analysis of recombination rate in male and female meioses. Genome 44, 589–596 (2001).

    CAS  PubMed  Google Scholar 

  150. 150.

    Sun, Z. et al. An ultradense genetic recombination map for Brassica napus, consisting of 13551 SRAP markers. Theor. Appl. Genet. 114, 1305–1317 (2007).

    CAS  PubMed  Google Scholar 

  151. 151.

    Bowers, J. E. et al. A high-density genetic recombination map of sequence-tagged sites for sorghum, as a framework for comparative structural and evolutionary genomics of tropical grains and grasses. Genetics 165, 367–386 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  152. 152.

    Pombi, M., Stump, A. D., Della Torre, A. & Besansky, N. J. Variation in recombination rate across the X chromosome of Anopheles gambiae. Am. J. Trop. Med. Hyg. 75, 901–903 (2006).

    CAS  PubMed  Google Scholar 

  153. 153.

    O’Connell, J. R. & Weeks, D. E. PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am. J. Hum. Genet. 63, 259–266 (1998).

    PubMed  PubMed Central  Google Scholar 

  154. 154.

    Blouin, M. S. DNA-based methods for pedigree reconstruction and kinship analysis in natural populations. Trends Ecol. Evol. 18, 503–511 (2003).

    Google Scholar 

  155. 155.

    Fierst, J. L. Using linkage maps to correct and scaffold de novo genome assemblies: methods, challenges, and computational tools. Front. Genet. 6, 220 (2015).

    PubMed  PubMed Central  Google Scholar 

  156. 156.

    Green, P., Falls, K. & Crooks, S. Documentation for CRI-MAP, version 2.4 (Washington Univ. School of Medicine, 1990).

  157. 157.

    Wu, Y., Bhat, P. R., Close, T. J. & Lonardi, S. Efficient and accurate construction of genetic linkage maps from the minimum spanning tree of a graph. PLoS Genet. 4, e1000212 (2008).

    PubMed  PubMed Central  Google Scholar 

  158. 158.

    Rastas, P. Lep-MAP3: robust linkage mapping even for low-coverage whole genome sequencing data. Bioinformatics 33, 3726–3732 (2017).

    CAS  PubMed  Google Scholar 

  159. 159.

    Rastas, P., Paulin, L., Hanski, I., Lehtonen, R. & Auvinen, P. Lep-MAP: fast and accurate linkage map construction for large SNP datasets. Bioinformatics 29, 3128–3134 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  160. 160.

    Miar, Y., Sargolzaei, M. & Schenkel, F. S. A comparison of different algorithms for phasing haplotypes using Holstein cattle genotypes and pedigree data. J. Dairy. Sci. 100, 2837–2849 (2017).

    CAS  PubMed  Google Scholar 

  161. 161.

    Hickey, J. M. et al. A combined long-range phasing and long haplotype imputation method to impute phase for SNP genotypes. Genet. Sel. Evol. 43, 12 (2011).

    PubMed  PubMed Central  Google Scholar 

  162. 162.

    DeWan, A. T., Parrado, A. R., Matise, T. C. & Leal, S. M. The map problem: a comparison of genetic and sequence-based physical maps. Am. J. Hum. Genet. 70, 101–107 (2002).

    CAS  PubMed  Google Scholar 

  163. 163.

    Zhao, H. & Speed, T. P. On genetic map functions. Genetics 142, 1369–1377 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. 164.

    Chakravarti, A. A graphical representation of genetic and physical maps: the Marey map. Genomics 11, 219–222 (1991).

    CAS  PubMed  Google Scholar 

  165. 165.

    Rezvoy, C., Charif, D., Guéguen, L. & Marais, G. A. B. MareyMap: an R-based tool with graphical interface for estimating recombination rates. Bioinformatics 23, 2188–2189 (2007).

    CAS  PubMed  Google Scholar 

  166. 166.

    Berloff, N., Perola, M. & Lange, K. Spline methods for the comparison of physical and genetic maps. J. Comput. Biol. 9, 465–475 (2002).

    CAS  PubMed  Google Scholar 

  167. 167.

    Yu, A. et al. Comparison of human genetic and sequence-based physical maps. Nature 409, 951–953 (2001).

    CAS  PubMed  Google Scholar 

  168. 168.

    Carrington, M. & Cullen, M. Justified chauvinism: advances in defining meiotic recombination through sperm typing. Trends Genet. 20, 196–205 (2004).

    CAS  PubMed  Google Scholar 

  169. 169.

    Sun, H. et al. Linked-read sequencing of gametes allows efficient genome-wide analysis of meiotic recombination. Nat. Commun. 10, 4310 (2019). This article is one of the first studies to perform bulk-gamete sequencing using linked-read technology to infer the recombination rate across the genome.

    PubMed  PubMed Central  Google Scholar 

  170. 170.

    Arbeithuber, B., Betancourt, A. J., Ebner, T. & Tiemann-Boege, I. Crossovers are associated with mutation and biased gene conversion at recombination hotspots. Proc. Natl Acad. Sci. USA 112, 2109–2114 (2015).

    CAS  PubMed  Google Scholar 

  171. 171.

    Li, H. H. et al. Amplification and analysis of DNA sequences in single human sperm and diploid cells. Nature 335, 414–417 (1988).

    CAS  PubMed  Google Scholar 

  172. 172.

    Huehn, M. On the bias of recombination fractions, Kosambi’s and Haldane’s distances based on frequencies of gametes. Genome 54, 196–201 (2011).

    PubMed  Google Scholar 

  173. 173.

    O’Reilly, P. F., Birney, E. & Balding, D. J. Confounding between recombination and selection, and the Ped/Pop method for detecting selection. Genome Res. 18, 1304–1313 (2008).

    PubMed  PubMed Central  Google Scholar 

  174. 174.

    Slotte, T. The impact of linked selection on plant genomic variation. Brief. Funct. Genomics 13, 268–275 (2014).

    PubMed  PubMed Central  Google Scholar 

  175. 175.

    Arenas, M., Lopes, J. S., Beaumont, M. A. & Posada, D. CodABC: a computational framework to coestimate recombination, substitution, and molecular adaptation rates by approximate Bayesian computation. Mol. Biol. Evol. 32, 1109–1112 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  176. 176.

    Hermann, P., Heissl, A., Tiemann-Boege, I. & Futschik, A. LDJump: estimating variable recombination rates from population genetic data. Mol. Ecol. Resour. 19, 623–638 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  177. 177.

    Beeravolu, C. R., Hickerson, M. J., Frantz, L. A. F. & Lohse, K. ABLE: blockwise site frequency spectra for inferring complex population histories and recombination. Genome Biol. 19, 145 (2018).

    PubMed  PubMed Central  Google Scholar 

  178. 178.

    Dréau, A., Venu, V., Avdievich, E., Gaspar, L. & Jones, F. C. Genome-wide recombination map construction from single individuals using linked-read sequencing. Nat. Commun. 10, 4309 (2019). This article is one of the first studies to perform bulk-gamete sequencing using linked-read technology to infer the recombination rate across the genome.

    PubMed  PubMed Central  Google Scholar 

  179. 179.

    Kawakami, T. et al. Whole-genome patterns of linkage disequilibrium across flycatcher populations clarify the causes and consequences of fine-scale recombination rate variation in birds. Mol. Ecol. 26, 4158–4172 (2017).

    CAS  PubMed  Google Scholar 

  180. 180.

    Smukowski Heil, C. S., Ellison, C., Dubin, M. & Noor, M. A. F. Recombining without hotspots: a comprehensive evolutionary portrait of recombination in two closely related species of Drosophila. Genome Biol. Evol. 7, 2829–2842 (2015).

    PubMed  PubMed Central  Google Scholar 

  181. 181.

    Gabriel, S. B. et al. The structure of haplotype blocks in the human genome. Science 296, 2225–2229 (2002).

    CAS  PubMed  Google Scholar 

  182. 182.

    Vijay, N. et al. Genomewide patterns of variation in genetic diversity are shared among populations, species and higher-order taxa. Mol. Ecol. 26, 4284–4295 (2017).

    PubMed  Google Scholar 

  183. 183.

    Paape, T. et al. Fine-scale population recombination rates, hotspots, and correlates of recombination in the Medicago truncatula genome. Genome Biol. Evol. 4, 726–737 (2012).

    PubMed  PubMed Central  Google Scholar 

  184. 184.

    Weissensteiner, M. H. et al. Combination of short-read, long-read, and optical mapping assemblies reveals large-scale tandem repeat arrays with population genetic implications. Genome Res. 27, 697–708 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  185. 185.

    Savolainen, O., Lascoux, M. & Merilä, J. Ecological genomics of local adaptation. Nat. Rev. Genet. 14, 807–820 (2013).

    CAS  PubMed  Google Scholar 

  186. 186.

    Ravinet, M. et al. Interpreting the genomic landscape of speciation: a road map for finding barriers to gene flow. J. Evol. Biol. 30, 1450–1477 (2017).

    CAS  PubMed  Google Scholar 

  187. 187.

    Wolf, J. B. W. & Ellegren, H. Making sense of genomic islands of differentiation in light of speciation. Nat. Rev. Genet. 18, 87–100 (2017).

    CAS  PubMed  Google Scholar 

  188. 188.

    Jeffreys, A. J. & Neumann, R. Factors influencing recombination frequency and distribution in a human meiotic crossover hotspot. Hum. Mol. Genet. 14, 2277–2287 (2005).

    CAS  PubMed  Google Scholar 

  189. 189.

    McGaugh, S. E. et al. Recombination modulates how selection affects linked sites in Drosophila. PLoS Biol. 10, e1001422 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  190. 190.

    Burri, R. et al. Linked selection and recombination rate variation drive the evolution of the genomic landscape of differentiation across the speciation continuum of Ficedula flycatchers. Genome Res. 25, 1656–1665 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  191. 191.

    Rueppell, O., Kuster, R., Miller, K. & Fouks, B. A new Metazoan recombination rate record and consistently high recombination rates in the honey bee genus Apis accompanied by frequent inversions but not translocations. Genome Biol. Evol. 8, 3653–3660 (2016).

    PubMed  PubMed Central  Google Scholar 

  192. 192.

    Guerrero, R. F., Rousset, F. & Kirkpatrick, M. Coalescent patterns for chromosomal inversions in divergent populations. Philos. Trans. R. Soc. Lond. B Biol. Sci. 367, 430–438 (2012).

    PubMed  PubMed Central  Google Scholar 

  193. 193.

    Jeffreys, A. J., Ritchie, A. & Neumann, R. High resolution analysis of haplotype diversity and meiotic crossover in the human TAP2 recombination hotspot. Hum. Mol. Genet. 9, 725–733 (2000).

    CAS  PubMed  Google Scholar 

  194. 194.

    Jeffreys, A. J., Neumann, R., Panayi, M., Myers, S. & Donnelly, P. Human recombination hot spots hidden in regions of strong marker association. Nat. Genet. 37, 601–606 (2005).

    CAS  PubMed  Google Scholar 

  195. 195.

    Morris, G. P. et al. Population genomic and genome-wide association studies of agroclimatic traits in sorghum. Proc. Natl Acad. Sci. USA 110, 453–458 (2013).

    CAS  PubMed  Google Scholar 

  196. 196.

    Knief, U. et al. Epistatic mutations under divergent selection govern phenotypic variation in the crow hybrid zone. Nat. Ecol. Evol. 3, 570–576 (2019).

    PubMed  PubMed Central  Google Scholar 

  197. 197.

    Roesti, M., Moser, D. & Berner, D. Recombination in the threespine stickleback genome—patterns and consequences. Mol. Ecol. 22, 3014–3027 (2013).

    CAS  PubMed  Google Scholar 

  198. 198.

    Liu, H. et al. Causes and consequences of crossing-over evidenced via a high-resolution recombinational landscape of the honey bee. Genome Biol. 16, 15 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  199. 199.

    Reddy, U. K. et al. High-resolution genetic map for understanding the effect of genome-wide recombination rate on nucleotide diversity in watermelon. G3 4, 2219–2230 (2014).

    PubMed  Google Scholar 

  200. 200.

    Palomar, G. et al. Comparative high-density linkage mapping reveals conserved genome structure but variation in levels of heterochiasmy and location of recombination cold spots in the common frog. G3 7, 637–645 (2017).

    CAS  PubMed  Google Scholar 

  201. 201.

    Jiang, H. et al. High recombination rates and hotspots in a Plasmodium falciparum genetic cross. Genome Biol. 12, R33 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  202. 202.

    van Oers, K. et al. Replicated high-density genetic maps of two great tit populations reveal fine-scale genomic departures from sex-equal recombination rates. Heredity 112, 307–316 (2014).

    PubMed  Google Scholar 

  203. 203.

    Tortereau, F. et al. A high density recombination map of the pig reveals a correlation between sex-specific recombination and GC content. BMC Genomics 13, 586 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  204. 204.

    Petit, M. et al. Variation in recombination rate and its genetic determinism in sheep populations. Genetics 207, 767–784 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  205. 205.

    Limborg, M. T., Waples, R. K., Allendorf, F. W. & Seeb, J. E. Linkage mapping reveals strong chiasma interference in sockeye salmon: implications for interpreting genomic data. G3 5, 2463–2473 (2015).

    CAS  PubMed  Google Scholar 

  206. 206.

    Collard, B. C. Y., Jahufer, M. Z. Z., Brouwer, J. B. & Pang, E. C. K. An introduction to markers, quantitative trait loci (QTL) mapping and marker-assisted selection for crop improvement: the basic concepts. Euphytica 142, 169–196 (2005).

    CAS  Google Scholar 

  207. 207.

    Yue, G. H. Recent advances of genome mapping and marker-assisted selection in aquaculture. Fish. Fish. 15, 376–396 (2014).

    Google Scholar 

  208. 208.

    Joron, M. et al. A conserved supergene locus controls colour pattern diversity in Heliconius butterflies. PLoS Biol. 4, e303 (2006).

    PubMed  PubMed Central  Google Scholar 

  209. 209.

    Dixon, G. B. et al. Genomic determinants of coral heat tolerance across latitudes. Science 348, 1460–1462 (2015).

    CAS  PubMed  Google Scholar 

  210. 210.

    Recoquillay, J. et al. A medium density genetic map and QTL for behavioral and production traits in Japanese quail. BMC Genomics 16, 10 (2015).

    PubMed  PubMed Central  Google Scholar 

  211. 211.

    Qiu, D. et al. A comparative linkage map of oilseed rape and its use for QTL analysis of seed oil and erucic acid content. Theor. Appl. Genet. 114, 67–80 (2006).

    CAS  PubMed  Google Scholar 

  212. 212.

    Cullen, M., Perfetto, S. P., Klitz, W., Nelson, G. & Carrington, M. High-resolution patterns of meiotic recombination across the human major histocompatibility complex. Am. J. Hum. Genet. 71, 759–776 (2002).

    PubMed  PubMed Central  Google Scholar 

  213. 213.

    Hubert, R., MacDonald, M., Gusella, J. & Arnheim, N. High resolution localization of recombination hot spots using sperm typing. Nat. Genet. 7, 420–424 (1994).

    CAS  PubMed  Google Scholar 

  214. 214.

    Yu, J. et al. Individual variation in recombination among human males. Am. J. Hum. Genet. 59, 1186–1192 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  215. 215.

    Lien, S., Szyda, J., Schechinger, B., Rappold, G. & Arnheim, N. Evidence for heterogeneity in recombination in the human pseudoautosomal region: high resolution analysis by sperm typing and radiation-hybrid mapping. Am. J. Hum. Genet. 66, 557–566 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  216. 216.

    Shi, Q. et al. Absence of age effect on meiotic recombination between human X and Y chromosomes. Am. J. Hum. Genet. 71, 254–261 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  217. 217.

    Hinch, A. G. et al. Factors influencing meiotic recombination revealed by whole-genome sequencing of single sperm. Science 363, eaau8861 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  218. 218.

    Shi, Q. et al. Single sperm typing demonstrates that reduced recombination is associated with the production of aneuploid 24,XY human sperm. Am. J. Med. Genet. 99, 34–38 (2001).

    CAS  PubMed  Google Scholar 

  219. 219.

    Wang, J., Fan, H. C., Behr, B. & Quake, S. R. Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell 150, 402–412 (2012). This influential study describes a method to genotype single human sperm cells and estimate recombination and mutation rates using a genome-wide sequencing approach.

    CAS  PubMed  PubMed Central  Google Scholar 

  220. 220.

    Williams, C., Davies, D. & Williamson, R. Segregation of ΔF508 and normal CFTR alleles in human sperm. Hum. Mol. Genet. 2, 445–448 (1993).

    CAS  PubMed  Google Scholar 

  221. 221.

    Dreissig, S., Fuchs, J., Himmelbach, A., Mascher, M. & Houben, A. Sequencing of single pollen nuclei reveals meiotic recombination events at megabase resolution and circumvents segregation distortion caused by postmeiotic processes. Front. Plant. Sci. 8, 1620 (2017).

    PubMed  PubMed Central  Google Scholar 

  222. 222.

    Ma, S., Ferguson, K. A., Arsovska, S., Moens, P. & Chow, V. Reduced recombination associated with the production of aneuploid sperm in an infertile man: a case report. Hum. Reprod. 21, 980–985 (2006).

    CAS  PubMed  Google Scholar 

  223. 223.

    Guryev, V. et al. Haplotype block structure is conserved across mammals. PLoS Genet. 2, e121 (2006).

    PubMed  PubMed Central  Google Scholar 

  224. 224.

    Tishkoff, S. A. & Verrelli, B. C. Role of evolutionary history on haplotype block structure in the human genome: implications for disease mapping. Curr. Opin. Genet. Dev. 13, 569–575 (2003).

    CAS  PubMed  Google Scholar 

  225. 225.

    Zhang, K., Calabrese, P., Nordborg, M. & Sun, F. Haplotype block structure and its applications to association studies: power and study designs. Am. J. Hum. Genet. 71, 1386–1394 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  226. 226.

    Ringbauer, H., Coop, G. & Barton, N. H. Inferring recent demography from isolation by distance of long shared sequence blocks. Genetics 205, 1335–1351 (2017).

    PubMed  PubMed Central  Google Scholar 

  227. 227.

    Sedghifar, A., Brandvain, Y. & Ralph, P. Beyond clines: lineages and haplotype blocks in hybrid zones. Mol. Ecol. 25, 2559–2576 (2016).

    PubMed  Google Scholar 

  228. 228.

    Laayouni, H. et al. Similarity in recombination rate estimates highly correlates with genetic differentiation in humans. PLoS One 6, e17913 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  229. 229.

    Sjödin, P., Kaj, I., Krone, S., Lascoux, M. & Nordborg, M. On the meaning and existence of an effective population size. Genetics 169, 1061–1070 (2005).

    PubMed  PubMed Central  Google Scholar 

  230. 230.

    Nachman, M. W. & Crowell, S. L. Estimate of the mutation rate per nucleotide in humans. Genetics 156, 297–304 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  231. 231.

    Smeds, L., Qvarnström, A. & Ellegren, H. Direct estimate of the rate of germline mutation in a bird. Genome Res. 26, 1211–1218 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  232. 232.

    Scally, A. The mutation rate in human evolution and demographic inference. Curr. Opin. Genet. Dev. 41, 36–43 (2016).

    CAS  PubMed  Google Scholar 

  233. 233.

    Auton, A. & McVean, G. Recombination rate estimation in the presence of hotspots. Genome Res. 17, 1219–1227 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  234. 234.

    Xu, S. et al. A male-specific genetic map of the microcrustacean Daphnia pulex based on single-sperm whole-genome sequencing. Genetics 201, 31–38 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  235. 235.

    Lu, S. et al. Probing meiotic recombination and aneuploidy of single sperm cells by whole-genome sequencing. Science 338, 1627–1630 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  236. 236.

    Gao, F., Ming, C., Hu, W. & Li, H. New software for the fast estimation of population recombination rates (FastEPRR) in the genomic era. G3 6, 1563–1571 (2016).

    CAS  PubMed  Google Scholar 

  237. 237.

    Wang, Y. & Rannala, B. Population genomic inference of recombination rates and hotspots. Proc. Natl Acad. Sci. USA 106, 6215–6219 (2009).

    CAS  PubMed  Google Scholar 

  238. 238.

    V Barroso, G., Puzović, N. & Dutheil, J. Y. Inference of recombination maps from a single pair of genomes and its application to ancient samples. PLoS Genet. 15, e1008449 (2019).

    PubMed  PubMed Central  Google Scholar 

  239. 239.

    McVean, G. A. T. et al. The fine-scale structure of recombination rate variation in the human genome. Science 304, 581–584 (2004).

    CAS  PubMed  Google Scholar 

  240. 240.

    Kamm, J. A., Spence, J. P., Chan, J. & Song, Y. S. Two-locus likelihoods under variable population size and fine-scale recombination rate estimation. Genetics 203, 1381–1399 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  241. 241.

    Wilson, D. J. & McVean, G. Estimating diversifying selection and functional constraint in the presence of recombination. Genetics 172, 1411–1425 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  242. 242.

    Humphreys, D. P., McGuirl, M. R., Miyagi, M. & Blumberg, A. J. Fast estimation of recombination rates using topological data analysis. Genetics 211, 1191–1204 (2019).

    PubMed  PubMed Central  Google Scholar 

  243. 243.

    Liu, D. et al. Construction and analysis of high-density linkage map using high-throughput sequencing data. PLoS One 9, e98855 (2014).

    PubMed  PubMed Central  Google Scholar 

  244. 244.

    van Ooijen, J. W. Multipoint maximum likelihood mapping in a full-sib family of an outbreeding species. Genet. Res. 93, 343–349 (2011).

    Google Scholar 

  245. 245.

    Rastas, P., Calboli, F. C. F., Guo, B., Shikano, T. & Merilä, J. Construction of ultradense linkage maps with Lep-MAP2: stickleback F2 recombinant crosses as an example. Genome Biol. Evol. 8, 78–93 (2015).

    PubMed  PubMed Central  Google Scholar 

  246. 246.

    Xu, P. et al. MRLR: unraveling high-resolution meiotic recombination by linked reads. Bioinformatics 36, 10–16 (2020).

    PubMed  Google Scholar 

  247. 247.

    Knowlton, S. M., Sadasivam, M. & Tasoglu, S. Microfluidics for sperm research. Trends Biotechnol. 33, 221–229 (2015).

    CAS  PubMed  Google Scholar 

  248. 248.

    Chen, M. et al. Comparison of multiple displacement amplification (MDA) and multiple annealing and looping-based amplification cycles (MALBAC) in single-cell sequencing. PLoS One 9, e114520 (2014).

    PubMed  PubMed Central  Google Scholar 

  249. 249.

    Huang, L., Ma, F., Chapman, A., Lu, S. & Xie, X. S. Single-cell whole-genome amplification and sequencing: methodology and applications. Annu. Rev. Genomics Hum. Genet. 16, 79–102 (2015).

    CAS  PubMed  Google Scholar 

  250. 250.

    Curik, I., Ferenčaković, M. & Sölkner, J. Inbreeding and runs of homozygosity: a possible solution to an old problem. Livest. Sci. 166, 26–34 (2014).

    Google Scholar 

  251. 251.

    Bahnak, B. R. et al. A simple and efficient method for isolating high molecular weight DNA from mammalian sperm. Nucleic Acids Res. 16, 1208 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  252. 252.

    Griffin, J. Methods of sperm DNA extraction for genetic and epigenetic studies. Methods Mol. Biol. 927, 379–384 (2013).

    CAS  PubMed  Google Scholar 

Download references


The authors thank the Dobzhansky Journal Club in the Division of Evolutionary Biology, LMU, Munich, for useful discussion and comments on this review. Funding was provided by the European Research Council (ERCStG-336536 FuncSpecGen) and LMU Munich.

Author information




J.V.P. wrote the manuscript. J.B.W.W. edited the manuscript before submission. Both authors researched data for the article and substantially contributed to the discussion of content.

Corresponding authors

Correspondence to Joshua V. Peñalba or Jochen B. W. Wolf.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Genetics thanks J. McAuley, S. Johnston and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

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


Genetic drift

A stochastic change in allele frequency from one generation to the next due to random sampling in finite populations.

Gene flow

The movement of chromosomes across genetically structured populations.

Genetic diversity

The total number of non-identical genetic elements in a population.


A set of co-inherited, physically linked genes often contributing to complex phenotypes.


A variation in recombination rates and, accordingly, genetic map length between sexes.

Heterogametic sex

The sex in which the sex chromosomes differ.

Structural variants

Any variations in the structure of a chromosome, including insertions, deletions, duplications, inversions or translocations.

Hill–Robertson interference

The reduction in the efficacy of selection when acting on alleles in physically linked genes.

Double-strand breaks

(DSBs). Lesions in the DNA double helix induced by a wide range of DNA-damaging agents. Programmed enzymatic induction during meiosis triggers homologous recombination.

Crossover interference

The non-random occurrence of multiple crossover events relative to each other during meiosis.

Gene conversion

The process whereby a fragment of DNA sequence is replaced by its homologue.

Crossover event

When a double-strand break (DSB) during meiosis results in exchange of homologous chromosomal regions. By contrast, a non-crossover event is when a DSB is repaired without homologous exchange of DNA material.

Recombination landscape

The variation in the local recombination rate plotted against the position along the chromosome.

Genetic mapping

A marker-based method to identify the order and genetic distance between loci.

Linkage disequilibrium

The non-random association of alleles at different loci.


A mathematical model describing the stochastic process of random reproduction backwards in time until all gene copies share a common ancestor. It predicts the distribution of gene genealogies of freely recombining segments of the genome.

Effective population size

(Ne). An abstract population genetic parameter describing the number of individuals in an idealized population in which the effect of genetic drift is representative of that in the real population.

Ancestral alleles

The allelic state of a locus that originated in the ancestral population. It is generally contrasted to the derived allele that arose by mutation in the evolutionary lineage or population under consideration.

Infinite sites model

A model in molecular evolution that assumes that there are an infinite number of sites where mutations can occur and that new mutations must occur in a novel site.

Four-gamete test

A test to detect historic recombination events by locating allelic combinations that could only have arisen as a result of recombination.

Ancestral recombination graph

A generalization of the coalescence tracing gene genealogies, integrating the recombination history of a population of samples.


The haplotype is inferred from genotype data.

Genotype likelihoods

The probabilities of genotypes, accounting for potential errors in the sequencing data that occur during sequencing and processing.

Linkage groups

Genetic markers that are inherited together as a unit, usually representing a chromosome.

Genetic map

Also known as linkage map. A representation of the order of genetic markers and inter-marker distance derived from the frequency of meiotic recombination.

Logarithm of the odds scores

(LOD scores). A statistical estimate of the likelihood that two entities are co-inherited, referring to the association of phenotypic and allelic variation or to the association between genotypes.

Physical map

The physical order of genetic markers along a chromosome.

Mapping functions

Algorithms to infer the additive genetic distance between two loci from measurable recombination fractions between them.

Haplotype blocks

Discrete stretches along the chromosome for which the phase can be unequivocally determined.

Demographic history

The history of a population with regard to change in size, structure and gene flow.

Whole-genome amplification

Genome-wide amplification of DNA, usually performed from DNA extracted from only one or a few cells.

Long-read sequencing

A class of DNA sequencing technologies and platforms that currently allows for sequencing of long (>20 kb) stretches of DNA.

Linked-read sequencing

A DNA library preparation method that incorporates unique barcodes to reads derived from a longer DNA molecule, such that the reads can be bioinformatically reassociated to the original DNA fragment.

Linked selection

A locus under selection causes corresponding changes in allele frequencies of other nearby loci owing to a lack of recombination between these loci.

Association mapping

A statistical approach to infer the association between phenotypes and genotypes.

Nucleotide diversity

A measure of genetic variation within a population or species, reflecting the average number of nucleotide differences between two chromosomes in a population.

Marker-assisted selection

Artificial selection whereby the founders for the next generation are selected on the basis of the genotype of a particular locus or set of loci underlying the phenotypic trait of interest.

Quantitative trait locus (QTL) mapping

A specific type of association mapping that focuses on a quantitative trait that is assumed to be encoded by multiple genes.

Meiotic drive

A mechanism acting during meiosis or gametogenesis that distorts the equal transmission of alleles.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Peñalba, J.V., Wolf, J.B.W. From molecules to populations: appreciating and estimating recombination rate variation. Nat Rev Genet 21, 476–492 (2020).

Download citation

Further reading


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