An evolutionary view of human recombination

• Published in: Nature reviews. Genetics Vol. 8; no. 1; pp. 23 - 34
• Main Authors: Coop, Graham, Przeworski, Molly
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2007; Nature Publishing Group
• Subjects: Agriculture; Animal Genetics and Genomics; Animals; Biological and medical sciences; Biological Evolution; Biomedical and Life Sciences; Biomedicine; Cancer Research; Crossing Over, Genetic; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Function; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Genome, Human; Human Genetics; Humans; Linkage Disequilibrium; Male; Mammals - genetics; Meiosis; Models, Genetic; Physiological aspects; Recombination, Genetic; review-article; Selection, Genetic; Sex Characteristics; Species Specificity; United States; Human; Molecular evolution; Recombination
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg1947

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. Despite the key role of recombination in meiosis, increasing evidence indicates substantial variation in recombination rates among humans, and between humans and other mammals. Understanding the forces that shape this variation will require a combination of evolutionary and molecular perspectives. 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.