Population Genetics of Lactase Persistence and Lactose Intolerance


Variation in the ability of adult humans to digest the lactose in milk is a genetically determined trait that has excited the interest of many for the past 50 years. The trait seems to have risen to high frequencies by one of the strongest selection pressures ever described. This section describes the phenotypic polymorphism and the evidence that the genetic trait involves regulation of expression of the lactase gene and is caused by multiple independent mutations that have reached high frequencies in different populations, because of the benefits of drinking milk. The evolutionary history in Europe and Africa are rather different; there being a single high‐frequency allele in Europe, in contrast to multiple alleles in Africa. Also the selective forces, which are likely to include both the nutritional and water content of milk, may have been different in these regions.

Key Concepts:

  • The enzyme, lactase, is restricted to the small intestine where it digests lactose in the milk of suckling mammals.

  • Lactase persists into adult life in some, but not all, people.

  • Lactase persistence is a genetic trait, which varies in frequency in different populations of the world.

  • Mutations in an enhancer sequence, at a distance from the lactase gene, appear to be responsible for lactase persistence.

  • These alleles arose in the last few thousand years and have been under strong positive selection.

  • The selection may be attributable to one of the nutrients or water in fresh milk and/or its calorific value.

Keywords: lactose; milk; lactase; selection; persistence; tolerance

Figure 1.

Old world distribution of frequency of lactase persistence (lactose digesters) taken from available published data. Red indicates the proportion of lactose digesters in a given population with yellow representing maldigesters. Charts with a green central circle indicate that the overall published frequency for a country is comprised of different ethnic groups with very different phenotype frequencies. Data compiled by Ingram et al. .

Figure 2.

Diagram of the MCM6 and LCT gene region, showing the location of the part of the enhancer region in which many variants are clustered and nucleotide changes identified, shown in red on the ancestral sequence. The approximate positions of the ones for which there is strong published evidence for association with lactase persistence as well as functional evidence are indicated. The corresponding rs numbers are: ‐14010 G>C, rs4988233;‐13915 T>G, rs41380347; ‐13910 C>T, rs4988235‐13907 C>G, rs41525747. Known transcription factor binding sites are underlined.



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Further Reading

Feldman MW and Cavalli‐Sforza LL (1989) On the theory of evolution under genetic and cultural transmission with application to the lactose absorption problem. In: Feldman M (ed.) Mathematical Evolutionary Theory, pp. 145–173. Princton, NJ: Princton University Press.

Swallow DM and Hollox EJ (2000) The genetic polymorphism of intestinal lactase activity in adult humans. In: Scriver CR, Beaudet AL, Sly WS and Valle D (eds) The Metabolic and Molecular Basis of Inherited Disease, 8th edn, chap. 76, pp. 1651–1662. New York: McGraw‐Hill. available online at http://www.ommbid.com/OMMBID/the_online_metabolic_and_molecular_bases_of_inherited_disease/b/parttoc/part7 updated 2007.

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Ingram, Catherine JE, Liebert, Anke, and Swallow, Dallas M(Dec 2012) Population Genetics of Lactase Persistence and Lactose Intolerance. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020855.pub2]