Balancing Selection in Human Evolution

Abstract

Selection can act to maintain alleles within a population through many mechanisms that, taken together, constitute balancing selection. Over the course of primate and human evolution, balancing selection has repeatedly acted upon the species. Though ancient causes and effects may never be fully known or appreciated, current, ongoing, balancing selection can be observed in the human genome today. This is particularly true in genes related to immune response and pathogen defence, reproductive fitness and environmental stressors. In understanding balancing selection, it is possible to see the history of humanity's natural challenges as well as evolution's response.

Keywords: balancing selection; human evolution; overdominance; MHC; human polymorphism

Figure 1.

Representative gene genealogies for loci evolving under neutral evolution (a) or balancing selection (b). Genes evolving under balancing selection will appear to have older coalescent times than genes evolving under neutrality. Alleles in genes under balancing selection will have an overrepresentation of high‐frequency mutations (c, open bars) relative to neutral expectation (c, filled bars).

Figure 2.

Select gene genealogy for the primate MHC gene, DQB1 (major histocompatibility complex, class II, DQ beta 1), with each terminal node representing an extant allele. Species of alleles bearing the alleles are indicated. Old World monkey species (baboon, rhesus macaque and African green monkey) are in shades of blue, ape species (gorilla, chimpanzee, human, orangutan and gibbon) are in shades of red, galago (a prosimian) is shown as an outgroup. Note that alleles do not uniformly cluster by species, indicating that allelic lineages predate speciation events. This tree includes only representative alleles. For a more complete examination see Otting et al..

Figure 3.

Distribution of malaria and malarial‐resistance genes in the Old World. The current distribution of endemic malaria (a) is paralleled by distributions of G6PD deficiency (b), sickle‐cell anaemia (c) and thalassaemia (d) in Africa, Europe, Asia and Australasia. Regions of northern Africa and southern Europe have historically dealt with malaria though it has largely been eradicated today.

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Further Reading

Bubb KL, Bovee D, Buckley D et al. (2006) Scan of human genome reveals no new loci under ancient balancing selection. Genetics 173: 2165–2177.

Cavalli‐Sforza LL, Menozzi P and Piazza A (1994) The History and Geography of Human Genes. Princeton, NJ: Princeton University Press.

Charlesworth D (2006) Balancing selection and its effects on sequences in nearby genome regions. PLoS Genetics 2: e64.

Hartl DL and Clark AG (1997) Darwinian selection. Principles of Population Genetics, 3rd edn, pp. 211–266. Sunderland, MA: Sinauer Associates, Inc.

Hedrick PW (2007) Balancing selection. Current Biology 17: R230–R231.

Hughes AL, Packer B, Welch R, Chanock SJ and Yeager M (2005) High level of functional polymorphism indicates a unique role of natural selection at human immune system loci. Immunogenetics 57: 821–827.

Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. American Journal of Human Genetics 77: 171–190.

Li WH (1997) DNA polymorphism in populations. Molecular Evolution, pp. 237–268. Sunderland, MA: Sinauer Associates, Inc.

Takahata N and Nei M (1990) Allelic genealogy under overdominant and frequency‐dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124: 967–978.

Tishkoff SA and Verrelli BC (2003) Patterns of human genetic diversity: implications for human evolutionary history and disease. Annual Review of Genomics and Human Genetics 4: 293–340.

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Vallender, Eric J, and Johnson, Welkin E(Apr 2008) Balancing Selection in Human Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020759]