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  • Review Article
  • Published:

An evolutionary view of human recombination

Key Points

  • Recombination has a key role in ensuring proper disjunction during meiosis, and in maintaining genome integrity. This role leads to a number of constraints on the recombination process.

  • Despite the importance of recombination in meiosis, there is a large variation in the number of crossover events among humans. This variation is more pronounced in females, but is also seen in males.

  • Recent studies have shown that there is extensive fine-scale heterogeneity in human recombination rates along the genome, with most events occurring in 'hotspots'. Activity of these hotspots seems to be modulated, at least in part, by sequence motifs that lie in cis.

  • Sperm-typing studies have shown that recombination hotspot intensities and locations vary among human males.

  • The selective forces that shape recombination rates are largely unknown. Selection that is related to the role of recombination in meiosis is bound to have an important role in shaping broad-scale rates. Furthermore, selection to maintain genome integrity, indirect selection on recombination modifiers and meiotic drive might influence fine-scale recombination rates. In particular, modifiers that increase recombination rates might have been favoured in regions that are subject to recurrent natural selection.

  • Mammalian species, even those that are closely related, differ in the length of their genetic map, the extent of sexual dimorphism for recombination rates, and their hotspot locations. These observations indicate that many aspects of recombination are not under strong constraint, but whether changes in these aspects are neutral or advantageous is an open question.

  • The increasing availability of genomic resources, coupled with the development of new statistical methods, should enable us to address enduring questions about the determinants of recombination and the selective pressures that influence them.

Abstract

Recombination has essential functions in mammalian meiosis, which impose several constraints on the recombination process. However, recent studies have shown that, in spite of these roles, recombination rates vary tremendously among humans, and show marked differences between humans and closely related species. These findings provide important insights into the determinants of recombination rates and raise new questions about the selective pressures that affect recombination over different genomic scales, with implications for human genetics and evolutionary biology.

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Figure 1: Genetic maps in mammals.
Figure 2: Heterogeneity in recombination rates along the human genome.
Figure 3: The genome-wide genetic map in humans and other primates.

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References

  1. Baker, B. S., Carpenter, A. T., Esposito, M. S., Esposito, R. E. & Sandler, L. The genetic control of meiosis. Annu. Rev. Genet. 10, 53–134 (1976).

    Article  CAS  PubMed  Google Scholar 

  2. Hassold, T. & Hunt, P. To err (meiotically) is human: the genesis of human aneuploidy. Nature Rev. Genet. 2, 280–291 (2001).

    Article  CAS  PubMed  Google Scholar 

  3. Inoue, K. & Lupski, J. R. Molecular mechanisms for genomic disorders. Annu. Rev. Genomics Hum. Genet. 3, 199–242 (2002).

    Article  CAS  PubMed  Google Scholar 

  4. Lynn, A., Ashley, T. & Hassold, T. Variation in human meiotic recombination. Annu. Rev. Genomics Hum. Genet. 5, 317–349 (2004). A panoramic review of variation in human meiotic recombination and its consequences, with a detailed description of experimental methods to study recombination.

    Article  CAS  PubMed  Google Scholar 

  5. Otto, S. P. & Lenormand, T. Resolving the paradox of sex and recombination. Nature Rev. Genet. 3, 252–261 (2002). An accessible and thorough review of evolutionary theories for the origin of sex and recombination.

    Article  CAS  PubMed  Google Scholar 

  6. Zickler, D. & Kleckner, N. Meiotic chromosomes: integrating structure and function. Annu. Rev. Genet. 33, 603–754 (1999).

    Article  CAS  PubMed  Google Scholar 

  7. Roeder, G. S. Meiotic chromosomes: it takes two to tango. Genes Dev. 11, 2600–2621 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Hawley, R. S. & Theurkauf, W. E. Requiem for distributive segregation: achiasmate segregation in Drosophila females. Trends Genet. 9, 310–317 (1993).

    Article  CAS  PubMed  Google Scholar 

  9. Sharp, P. Sex chromosome pairing during male meiosis in marsupials. Chromosoma 86, 27–47 (1982).

    Article  CAS  PubMed  Google Scholar 

  10. Zwick, M. E., Cutler, D. J. & Langley, C. H. Classic Weinstein: tetrad analysis, genetic variation and achiasmate segregation in Drosophila and humans. Genetics 152, 1615–1629 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. de Massy, B. Distribution of meiotic recombination sites. Trends Genet. 19, 514–522 (2003).

    Article  CAS  PubMed  Google Scholar 

  12. Hassold, T. et al. Cytological studies of meiotic recombination in human males. Cytogenet. Genome Res. 107, 249–255 (2004).

    Article  CAS  PubMed  Google Scholar 

  13. Pardo-Manuel de Villena, F. & Sapienza, C. Recombination is proportional to the number of chromosome arms in mammals. Mamm. Genome 12, 318–322 (2001). Demonstrates that the number of chromosomal arms (excluding short arms of acrocentric chromosomes) is a good predictor of genetic maps, whether these are constructed from pedigrees or from chiasmata counts.

    Article  CAS  PubMed  Google Scholar 

  14. Broman, K. W. & Weber, J. L. Characterization of human crossover interference. Am. J. Hum. Genet. 66, 1911–1926 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Broman, K. W., Rowe, L. B., Churchill, G. A. & Paigen, K. Crossover interference in the mouse. Genetics 160, 1123–1131 (2002).

    PubMed  PubMed Central  Google Scholar 

  16. Kaback, D. B., Barber, D., Mahon, J., Lamb, J. & You, J. Chromosome size-dependent control of meiotic reciprocal recombination in Saccharomyces cerevisiae: the role of crossover interference. Genetics 152, 1475–1486 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Bishop, D. K. & Zickler, D. Early decision; meiotic crossover interference prior to stable strand exchange and synapsis. Cell 117, 9–15 (2004).

    Article  CAS  PubMed  Google Scholar 

  18. Chua, P. R. & Roeder, G. S. Tam1, a telomere-associated meiotic protein, functions in chromosome synapsis and crossover interference. Genes Dev. 11, 1786–1800 (1997).

    Article  CAS  PubMed  Google Scholar 

  19. Jensen-Seaman, M. I. et al. Comparative recombination rates in the rat, mouse, and human genomes. Genome Res. 14, 528–538 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Petes, T. D. Meiotic recombination hot spots and cold spots. Nature Rev. Genet. 2, 360–369 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Kong, A. et al. A high-resolution recombination map of the human genome. Nature Genet. 31, 241–247 (2002). The most accurate genetic map that is available in humans, constructed on the basis of 1,257 meioses and 5,136 microsatellite markers.

    Article  CAS  PubMed  Google Scholar 

  22. Hellmann, I. et al. Why do human diversity levels vary at a megabase scale? Genome Res. 15, 1222–1231 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hellmann, I., Ebersberger, I., Ptak, S. E., Paabo, S. & Przeworski, M. A neutral explanation for the correlation of diversity with recombination rates in humans. Am. J. Hum. Genet. 72, 1527–1535 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rattray, A. J., McGill, C. B., Shafer, B. K. & Strathern, J. N. Fidelity of mitotic double-strand-break repair in Saccharomyces cerevisiae: a role for SAE2/COM1. Genetics 158, 109–122 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Spencer, C. et al. The influence of recombination on human genetic diversity. PLoS Genet. 2, 1375–1385 (2006). A careful examination of the associations between diversity, divergence, genomic features and fine-scale recombination (inferred from LD patterns) on chromosome 20. The authors find evidence for biased gene conversion in recombination hotspots.

    Article  CAS  Google Scholar 

  26. Jeffreys, A. J. et al. Meiotic recombination hot spots and human DNA diversity. Philos. Trans. R. Soc. Lond. B Biol. Sci. 359, 141–152 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Arnheim, N., Calabrese, P. & Nordborg, M. Hot and cold spots of recombination in the human genome: the reason we should find them and how this can be achieved. Am. J. Hum. Genet. 73, 5–16 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kauppi, L., Jeffreys, A. J. & Keeney, S. Where the crossovers are: recombination distributions in mammals. Nature Rev. Genet. 5, 413–424 (2004). An interesting review of recent discoveries about recombination-rate heterogeneity in mammals, with an emphasis on sperm-typing experiments.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  30. Jeffreys, A. J. & May, C. A. Intense and highly localized gene conversion activity in human meiotic crossover hot spots. Nature Genet. 36, 151–156 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Holloway, K., Lawson, V. E. & Jeffreys, A. J. Allelic recombination and de novo deletions in sperm in the human β-globin gene region. Hum. Mol. Genet. 15, 1099–1111 (2006).

    Article  CAS  PubMed  Google Scholar 

  32. Gaut, B. S., Wright, S. I., Rizzon, C., Anderson, L. K. & Dvorak, J. Recombination: an underappreciated factor in the evolution of plant genomes. Nature Rev. Genet. (in the press).

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

    Article  CAS  PubMed  Google Scholar 

  34. 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). Constructs a fine-scale genetic map in humans from genome-wide patterns of LD. The authors find a set of sequence motifs that are overrepresented in hotspots relative to coldspots, two of which have been shown to modulate hotspot activity in sperm.

    Article  CAS  PubMed  Google Scholar 

  35. Koren, A., Ben-Aroya, S. & Kupiec, M. Control of meiotic recombination initiation: a role for the environment? Curr. Genet. 42, 129–139 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Li, W. -H. Molecular Evolution (Sinauer Associates, Sunderland, 1997).

    Google Scholar 

  37. Steiner, W. W. & Smith, G. R. Optimizing the nucleotide sequence of a meiotic recombination hotspot in Schizosaccharomyces pombe. Genetics 169, 1973–1983 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Birdsell, J. A. Integrating genomics, bioinformatics, and classical genetics to study the effects of recombination on genome evolution. Mol. Biol. Evol. 19, 1181–1197 (2002).

    Article  CAS  PubMed  Google Scholar 

  39. Lindsay, S. J., Khajavi, M., Lupski, J. R. & Hurles, M. E. A chromosomal rearrangement hotspot can be identified from population genetic variation, and is co-incident with a hotspot for allelic recombination. Am. J. Hum. Genet. 79, 890–902 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Broman, K. W., Murray, J. C., Sheffield, V. C., White, R. L. & Weber, J. L. Comprehensive human genetic maps: individual and sex-specific variation in recombination. Am. J. Hum. Genet. 63, 861–869 (1998). An early genetic map for humans, and the first such study to show variation among females and systematic differences between the male and female recombination landscape on every chromosome.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Daw, E. W., Thompson, E. A. & Wijsman, E. M. Bias in multipoint linkage analysis arising from map misspecification. Genet. Epidemiol. 19, 366–380 (2000).

    Article  CAS  PubMed  Google Scholar 

  42. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  43. Smith, R. A., Ho, P. J., Clegg, J. B., Kidd, J. R. & Thein, S. L. Recombination breakpoints in the human β-globin gene cluster. Blood 92, 4415–4421 (1998).

    CAS  PubMed  Google Scholar 

  44. Shiroishi, T., Koide, T., Yoshino, M., Sagai, T. & Moriwaki, K. Hotspots of homologous recombination in mouse meiosis. Adv. Biophys. 31, 119–132 (1995).

    Article  CAS  PubMed  Google Scholar 

  45. Hunt, P. A. & Hassold, T. J. Sex matters in meiosis. Science 296, 2181–2183 (2002).

    Article  CAS  PubMed  Google Scholar 

  46. Morelli, M. A. & Cohen, P. E. Not all germ cells are created equal: aspects of sexual dimorphism in mammalian meiosis. Reproduction 130, 761–781 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Tease, C. & Hulten, M. A. Inter-sex variation in synaptonemal complex lengths largely determine the different recombination rates in male and female germ cells. Cytogenet. Genome Res. 107, 208–215 (2004).

    Article  CAS  PubMed  Google Scholar 

  48. Lenzi, M. L. et al. Extreme heterogeneity in the molecular events leading to the establishment of chiasmata during meiosis I in human oocytes. Am. J. Hum. Genet. 76, 112–127 (2005). The largest study of MLH1 foci in oocytes, finding large variation in foci counts within and among females.

    Article  CAS  PubMed  Google Scholar 

  49. Kong, A. et al. Recombination rate and reproductive success in humans. Nature Genet. 36, 1203–1206 (2004). A study of the relationship between fertility, maternal age and recombination. The authors find that older mothers tend to transmit chromosomes with more crossing over to viable offspring, and that mothers with higher crossing-over rates have slightly more children on average.

    Article  CAS  PubMed  Google Scholar 

  50. Vallente, R. U., Cheng, E. Y. & Hassold, T. J. The synaptonemal complex and meiotic recombination in humans: new approaches to old questions. Chromosoma 115, 241–249 (2006).

    Article  PubMed  Google Scholar 

  51. Lamb, N. E. et al. Susceptible chiasmate configurations of chromosome 21 predispose to non-disjunction in both maternal meiosis I and meiosis II. Nature Genet. 14, 400–405 (1996).

    Article  CAS  PubMed  Google Scholar 

  52. Lamb, N. E., Yu, K., Shaffer, J., Feingold, E. & Sherman, S. L. Association between maternal age and meiotic recombination for trisomy 21. Am. J. Hum. Genet. 76, 91–99 (2005).

    Article  CAS  PubMed  Google Scholar 

  53. Sun, F. et al. Human male recombination maps for individual chromosomes. Am. J. Hum. Genet. 74, 521–531 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  55. Dumas, D. & Britton-Davidian, J. Chromosomal rearrangements and evolution of recombination: comparison of chiasma distribution patterns in standard and robertsonian populations of the house mouse. Genetics 162, 1355–1366 (2002).

    PubMed  PubMed Central  Google Scholar 

  56. Giglio, S. et al. Olfactory receptor-gene clusters, genomic-inversion polymorphisms, and common chromosome rearrangements. Am. J. Hum. Genet. 68, 874–883 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Stefansson, H. et al. A common inversion under selection in Europeans. Nature Genet. 37, 129–137 (2005).

    Article  CAS  PubMed  Google Scholar 

  58. Schultz, J. & Redfield, H. Interchromosomal effects on crossing over in Drosophila. Cold Spring Harb. Symp. Quant. Biol. 16, 175–197 (1951).

    Article  CAS  PubMed  Google Scholar 

  59. Anton, E., Blanco, J., Egozcue, J. & Vidal, F. Sperm studies in heterozygote inversion carriers: a review. Cytogenet. Genome Res. 111, 297–304 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  61. 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 

  62. 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). A detailed sperm-typing study of the human pseudoautosomal region, which finds significant variation in crossing-over rates at fine scales.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Neumann, R. & Jeffreys, A. J. Polymorphism in the activity of human crossover hotspots independent of local DNA sequence variation. Hum. Mol. Genet. 15, 1401–1411 (2006).

    Article  CAS  PubMed  Google Scholar 

  64. Tiemann-Boege, I., Calabrese, P., Cochran, D. M., Sokol, R. & Arnheim, N. High-resolution recombination patterns in a region of human chromosome 21 measured by sperm typing. PLoS Genet. 2, e70 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Jeffreys, A. J. & Neumann, R. Reciprocal crossover asymmetry and meiotic drive in a human recombination hot spot. Nature Genet. 31, 267–271 (2002).

    Article  CAS  PubMed  Google Scholar 

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

  67. Robinson, W. P. et al. Maternal meiosis I non-disjunction of chromosome 15: dependence of the maternal age effect on level of recombination. Hum. Mol. Genet. 7, 1011–1019 (1998).

    Article  CAS  PubMed  Google Scholar 

  68. Rose, M. R. The Evolutionary Biology of Ageing, (Oxford Univ. Press, Oxford, 1991).

    Google Scholar 

  69. Williams, G. C. Pleiotropy, natural selection and the evolution of senescence. Evolution 11, 398–411 (1957).

    Article  Google Scholar 

  70. Bailey, J. A. & Eichler, E. E. Primate segmental duplications: crucibles of evolution, diversity and disease. Nature Rev. Genet. 7, 552–564 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Hill, W. G. & Robertson, A. The effect of linkage on limits to artificial selection. Genet Res. 8, 269–294 (1966).

    Article  CAS  PubMed  Google Scholar 

  72. Feldman, M. W., Otto, S. P. & Christiansen, F. B. Population genetic perspectives on the evolution of recombination. Annu. Rev. Genet. 30, 261–295 (1996).

    Article  CAS  PubMed  Google Scholar 

  73. Stone, A. C. & Verrelli, B. C. Focusing on comparative ape population genomics in the post-genomic age. Curr. Opin. Genet. Dev. 16, 586–591 (2006).

    Article  CAS  PubMed  Google Scholar 

  74. Otto, S. P. & Barton, N. H. Selection for recombination in small populations. Evolution 55, 1921–1931 (2001).

    Article  CAS  PubMed  Google Scholar 

  75. Charlesworth, D., Charlesworth, B. & Marais, G. Steps in the evolution of heteromorphic sex chromosomes. Heredity 95, 118–128 (2005).

    Article  CAS  PubMed  Google Scholar 

  76. Burt, A. & Bell, G. Mammalian chiasma frequencies as a test of two theories of recombination. Nature 326, 803–805 (1987).

    Article  CAS  PubMed  Google Scholar 

  77. Ross-Ibarra, J. The evolution of recombination under domestication: a test of two hypotheses. Am. Nat. 163, 105–112 (2004).

    Article  PubMed  Google Scholar 

  78. Flexon, P. B. & Rodell, C. F. Genetic recombination and directional selection for DDT resistance in Drosophila melanogaster. Nature 298, 672–674 (1982).

    Article  CAS  PubMed  Google Scholar 

  79. Korol, A. B. & Iliadi, K. G. Increased recombination frequencies resulting from directional selection for geotaxis in Drosophila. Heredity 72, 64–68 (1994).

    Article  PubMed  Google Scholar 

  80. Bourguet, D., Gair, J., Mattice, M. & Whitlock, M. C. Genetic recombination and adaptation to fluctuating environments: selection for geotaxis in Drosophila melanogaster. Heredity 91, 78–84 (2003).

    Article  CAS  PubMed  Google Scholar 

  81. Bachtrog, D. Protein evolution and codon usage bias on the neo-sex chromosomes of Drosophila miranda. Genetics 165, 1221–1232 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Kliman, R. M. & Hey, J. Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol. Biol. Evol. 10, 1239–1258 (1993).

    CAS  PubMed  Google Scholar 

  83. Presgraves, D. C. Recombination enhances protein adaptation in Drosophila melanogaster. Curr. Biol. 15, 1651–1656 (2005).

    Article  CAS  PubMed  Google Scholar 

  84. Marais, G., Nouvellet, P., Keightley, P. D. & Charlesworth, B. Intron size and exon evolution in Drosophila. Genetics 170, 481–485 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Zwick, M. E., Salstrom, J. L. & Langley, C. H. Genetic variation in rates of nondisjunction: association of two naturally occurring polymorphisms in the chromokinesin nod with increased rates of nondisjunction in Drosophila melanogaster. Genetics 152, 1605–1614 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Boulton, A., Myers, R. S. & Redfield, R. J. The hotspot conversion paradox and the evolution of meiotic recombination. Proc. Natl Acad. Sci. USA 94, 8058–8063 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Pineda-Krch, M. & Redfield, R. J. Persistence and loss of meiotic recombination hotspots. Genetics 169, 2319–2333 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Sturtevant, A. H. The genetics of Drosophila simulans. Carnegie Inst. Washington Publ. 399, 1–62. (1929).

    Google Scholar 

  89. True, J. R., Mercer, J. M. & Laurie, C. C. Differences in crossover frequency and distribution among three sibling species of Drosophila. Genetics 142, 507–523 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Samollow, P. B. et al. First-generation linkage map of the gray, short-tailed opossum, Monodelphis domestica, reveals genome-wide reduction in female recombination rates. Genetics 166, 307–329 (2004). The second sex-specific genetic map in marsupials to find greater recombination in males. The authors place their findings in a wider comparative-genomics context.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Wall, J. D., Frisse, L. A., Hudson, R. R. & Di Rienzo, A. Comparative linkage-disequilibrium analysis of the β-globin hotspot in primates. Am. J. Hum. Genet. 73, 1330–1340 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Ptak, S. E. et al. Absence of the TAP2 human recombination hotspot in chimpanzees. PLoS Biol. 2, 849–855 (2004).

    Article  CAS  Google Scholar 

  93. Ptak, S. E. et al. Fine-scale recombination patterns differ between chimpanzees and humans. Nature Genet. 37, 429–434 (2005).

    Article  CAS  PubMed  Google Scholar 

  94. Winckler, W. et al. Comparison of fine-scale recombination rates in humans and chimpanzees. Science 308, 107–111 (2005).

    Article  CAS  PubMed  Google Scholar 

  95. Kauppi, L., Stumpf, M. P. & Jeffreys, A. J. Localized breakdown in linkage disequilibrium does not always predict sperm crossover hot spots in the human MHC class II region. Genomics 86, 13–24 (2005).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  98. Keeney, S. et al. A mouse homolog of the Saccharomyces cerevisiae meiotic recombination DNA transesterase Spo11p. Genomics 61, 170–182 (1999).

    Article  CAS  PubMed  Google Scholar 

  99. Stephan, W., Song, Y. S. & Langley, C. H. The hitchhiking effect on linkage disequilibrium between linked neutral loci. Genetics 172, 2647–2663 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Charlesworth, D., Charlesworth, B. & Morgan, M. T. The pattern of neutral molecular variation under the background selection model. Genetics 141, 1619–1632 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Gilad, Y., Oshlack, A. & Rifkin, S. A. Natural selection on gene expression. Trends Genet. 8, 456–461 (2006).

    Article  CAS  Google Scholar 

  102. Kidwell, M. G. Genetic change of recombination value in Drosophila melanogaster. I. Artificial selection for high and low recombination and some properties of recombination-modifying genes. Genetics 70, 419–432 (1971).

    Google Scholar 

  103. Barlow, A. L. & Hulten, M. A. Crossing over analysis at pachytene in man. Eur. J. Hum. Genet. 6, 350–358 (1998).

    Article  CAS  PubMed  Google Scholar 

  104. Hudson, R. R. Properties of a neutral allele model with intragenic recombination. Theor. Popul. Biol. 23, 183–201 (1983).

    Article  CAS  PubMed  Google Scholar 

  105. Hellenthal, G. & Stephens, M. Insights into recombination from population genetic variation. Curr. Opin. Genet. Dev. 16, 565–572 (2006). A nice review of the methods to infer recombination-rate variation from genetic variation data and the findings that have emerged from the application of such methods.

    Article  CAS  PubMed  Google Scholar 

  106. Li, N. & Stephens, M. Modeling linkage disequilibrium and identifying recombination hotspots using single-nucleotide polymorphism data. Genetics 165, 2213–2233 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Smith, N. G. & Fearnhead, P. A comparison of three estimators of the population-scaled recombination rate: accuracy and robustness. Genetics 171, 2051–2062 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Nielsen, R. & Signorovitch, J. Correcting for ascertainment biases when analyzing SNP data: applications to the estimation of linkage disequilibrium. Theor. Popul. Biol. 63, 245–255 (2003).

    Article  PubMed  Google Scholar 

  109. Brooks, L. D. in The Evolution Of Sex: An Examination Of Current Ideas (eds Michod, R. E. & Levin, B. R.) 87–105 (Sinauer Associates, Sutherland, 1988).

    Google Scholar 

  110. Reeves, R. H., Crowley, M. R., O'Hara, B. F. & Gearhart, J. D. Sex, strain, and species differences affect recombination across an evolutionarily conserved segment of mouse chromosome 16. Genomics 8, 141–148 (1990).

    Article  CAS  PubMed  Google Scholar 

  111. Koehler, K. E., Cherry, J. P., Lynn, A., Hunt, P. A. & Hassold, T. J. Genetic control of mammalian meiotic recombination. I. Variation in exchange frequencies among males from inbred mouse strains. Genetics 162, 297–306 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Williams, C. G., Goodman, M. M. & Stuber, C. W. Comparative recombination distances among Zea mays L. inbreds, wide crosses and interspecific hybrids. Genetics 141, 1573–1581 (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Brooks, L. D. & Marks, R. W. The organization of genetic variation for recombination in Drosophila melanogaster. Genetics 114, 525–547 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Saleem, M., Lamb, B. C. & Nevo, E. Inherited differences in crossing over and gene conversion frequencies between wild strains of Sordaria fimicola from 'Evolution Canyon'. Genetics 159, 1573–1593 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Felsenstein, J. & Yokoyama, S. The evolutionary advantage of recombination. II. Individual selection for recombination. Genetics 83, 845–859 (1976).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Iles, M. M., Walters, K. & Cannings, C. Recombination can evolve in large finite populations given selection on sufficient loci. Genetics 165, 2249–2258 (2003).

    PubMed  PubMed Central  Google Scholar 

  118. Keightley, P. D. & Otto, S. P. Interference among deleterious mutations favours sex and recombination in finite populations. Nature 443, 89–92 (2006).

    Article  CAS  PubMed  Google Scholar 

  119. Peck, J. R. A ruby in the rubbish: beneficial mutations, deleterious mutations and the evolution of sex. Genetics 137, 597–606 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  121. Burt, A., Bell, G. & Harvey, P. H. Sex-differences in recombination. J. Evol. Biol. 4, 259–277 (1991).

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  Google Scholar 

  124. Trivers, R. L. in The Evolution Of Sex (eds Michod, R. E. & Levin, B. R.) 270–286 (Sinauer Associates, Sunderland, 1988).

    Google Scholar 

  125. Lynn, A., Schrump, S., Cherry, J., Hassold, T. & Hunt, P. Sex, not genotype, determines recombination levels in mice. Am. J. Hum. Genet. 77, 670–675 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Hansson, B., Akesson, M., Slate, J. & Pemberton, J. M. Linkage mapping reveals sex-dimorphic map distances in a passerine bird. Proc. Biol. Sci. 272, 2289–2298 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Lenormand, T. The evolution of sex dimorphism in recombination. Genetics 163, 811–822 (2003).

    PubMed  PubMed Central  Google Scholar 

  128. Lercher, M. J. & Hurst, L. D. Imprinted chromosomal regions of the human genome have unusually high recombination rates. Genetics 165, 1629–1632 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Paldi, A., Gyapay, G. & Jami, J. Imprinted chromosomal regions of the human genome display sex-specific meiotic recombination frequencies. Curr. Biol. 5, 1030–1035 (1995).

    Article  CAS  PubMed  Google Scholar 

  130. Cox, L. A., Mahaney, M. C., Vandeberg, J. L. & Rogers, J. A second-generation genetic linkage map of the baboon (Papio hamadryas) genome. Genomics 88, 274–281 (2006).

    Article  CAS  PubMed  Google Scholar 

  131. Rogers, J. et al. An initial genetic linkage map of the rhesus macaque (Macaca mulatta) genome using human microsatellite loci. Genomics 87, 30–38 (2006).

    Article  CAS  PubMed  Google Scholar 

  132. Steen, R. G. et al. A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat. Genome Res. 9, AP1–AP8 (1999).

    CAS  PubMed  Google Scholar 

  133. Okuizumi, H. et al. Linkage map of Syrian hamster with restriction landmark genomic scanning. Mamm. Genome 8, 121–128 (1997).

    Article  CAS  PubMed  Google Scholar 

  134. Dietrich, W. F. et al. A comprehensive genetic map of the mouse genome. Nature 380, 149–152 (1996).

    Article  CAS  PubMed  Google Scholar 

  135. Menotti-Raymond, M. et al. A genetic linkage map of microsatellites in the domestic cat (Felis catus). Genomics 57, 9–23 (1999).

    Article  CAS  PubMed  Google Scholar 

  136. Ihara, N. et al. A comprehensive genetic map of the cattle genome based on 3,802 microsatellites. Genome Res. 14, 1987–1998 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Maddox, J. F. et al. An enhanced linkage map of the sheep genome comprising more than 1,000 loci. Genome Res. 11, 1275–1289 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Neff, M. W. et al. A second-generation genetic linkage map of the domestic dog, Canis familiaris. Genetics 151, 803–820 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Mikawa, S. et al. A linkage map of 243 DNA markers in an intercross of Gottingen miniature and Meishan pigs. Anim. Genet. 30, 407–417 (1999).

    Article  CAS  PubMed  Google Scholar 

  140. Zenger, K. R., McKenzie, L. M. & Cooper, D. W. The first comprehensive genetic linkage map of a marsupial: the tammar wallaby (Macropus eugenii). Genetics 162, 321–330 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Alsop, A. E. et al. Characterizing the chromosomes of the Australian model marsupial Macropus eugenii (tammar wallaby). Chromosome Res. 13, 627–636 (2005).

    Article  CAS  PubMed  Google Scholar 

  142. Pathak, S., Ronne, M., Brown, N. M., Furlong, C. L. & VandeBerg, J. L. A high-resolution banding pattern idiogram of Monodelphis domestica chromosomes (Marsupialia, Mammalia). Cytogenet. Cell Genet. 63, 181–184 (1993).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Many thanks to D. Bishop, B. Charlesworth, D. Charlesworth, D. Conrad, G. Hellenthal, Y. Gilad, T. Hassold, J. Pritchard and three anonymous reviewers for helpful comments on the manuscript, as well as to P. Andolfatto, B. Charlesworth and T. Hassold for helpful discussions. G.C. is supported by an NIH grant to J. K. Pritchard. M.P. is supported by an Alfred P. Sloan Fellowship in Computational and Evolutionary Molecular Biology.

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DATABASES

Entrez Gene

MLH1

Spo11

FURTHER INFORMATION

University of Chicago Department of Human Genetics

Glossary

Disjunction

The segregation of homologous chromosomes during meiosis.

Aneuploidy

Having more or less than the typical chromosome number (46 for humans).

Ectopic exchange

Homologous recombination between non-allelic copies.

Haplotype

The combination of alleles on a chromosome.

Synapsis

A process through which homologous chromosomes are brought into close alignment with one another.

Crossing over

A type of homologous-recombination event during which there is a reciprocal exchange of flanking regions. Also referred to as a crossover.

Chromatid

An individual daughter chromosome after replication.

Bivalent

A pair of homologous chromosomes after replication; each chromosome consists of two chromatids.

Holliday junction

An intermediate step in homologous recombination; the point of exchange between four strands of DNA.

Gene conversion

Recombination that involves non-reciprocal exchange of a small segment of a chromosome. We note that this population-genetic definition differs from the more widespread definition, which is based on non-Mendelian segregation.

Metacentric

Chromosomes in which the centromere is not close to either end.

Acrocentric

Chromosomes in which the centromere is close to one end.

Genetic map

A map of markers along the genome, in which the distance between markers reflects the recombination frequencies between them. The longer the total genetic map, the more recombination occurs in the genome. Also referred to as a linkage map.

Positive interference

The process through which a crossover event reduces the probability of a second such event in its neighborhood.

Recombination hotspot

A short segment of DNA that experiences much more recombination than the flanking regions.

Linkage disequilibrium

In a sample, an association of alleles at different loci beyond what would be expected by chance.

Chiasma

Connection between homologous chromosomes resulting from crossing over.

Population recombination rate

Usually defined as 4Nr, where N is the effective population size and r the recombination rate per meiosis.

Biased gene conversion

A bias in the process of gene conversion in favour of one type of allele over another, also referred to as disparity of gene conversion.

Interchromosomal effect

In heterozygotes, the effect of an inversion on recombination rates on other chromosomes.

Pseudoautosomal region 1

A region of homology between the X and Y chromosomes that experiences obligate crossing over in males.

Antagonistic pleiotropy

The case in which a single loci has multiple effects, some advantageous and some deleterious; for example, when a gene causes higher fitness early in life, but decreased fitness at older ages.

Negative disequilibrium

Two alleles are in negative linkage disequilibrium if they are found on different chromosomes more often than expected by chance.

Effective population size

Reflects the extent of genetic drift and can be far lower than the census population size.

Meiotic drive

Any non-adaptive process that leads an allele to be over-transmitted in gametes during meiosis.

Heterogametic sex

The sex that has differently shaped sex chromosomes. In mammals, the heterogametic sex is male (XY) and homogametic sex is female (XX), whereas in other species, such as birds, the heterogametic sex is female (ZW).

Background selection

The effect of strong purifying selection on linked neutral variation.

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Coop, G., Przeworski, M. An evolutionary view of human recombination. Nat Rev Genet 8, 23–34 (2007). https://doi.org/10.1038/nrg1947

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