Primary adult lactose intolerance and the milking habit : a problem in biologic and cultural interrelations II. A culture historical hypothesis
01 Aug 1970-Digestive Diseases and Sciences (Kluwer Academic Publishers)-Vol. 15, Iss: 8, pp 695-710
TL;DR: In this paper, the conditions of genetic selection that may have led some groups of men to have persistently high levels of intestinal lactase throughout life, and others not, are considered.
Abstract: The principal conclusion reached in Part I of this article (1) was that the group differences found in primary adult lactose intolerance among the world's peoples are largely genetic in origin. In this part, after a review of recent research that adds to Part I in important ways, we turn to a consideration of the conditions of genetic selection that may have led some groups of men to have persistently high levels of intestinal lactase throughout life, and others not. Low incidence of intolerance, it is held, would develop over time in a group that has an abundant milk supply, that has alternate foodstuffs inadequate in amount and quality, and that consumes milk in lactose-rich forms. Since such selection cannot have occurred among groups that did not use milk, areas of nonmilking in the modern world are first delimited. The origins and diffusion of dairying are then sketched to determine the length of time that milk was consumed in various regions. With the background thus gained, the present-day occurrence of various Old World groups with high and low incidences of intolerance is explained. All groups studied so far within the traditional areas of nonmilking are found to have high incidences of intolerance. Overseas groups, such as American Negroes, whose ancestors came from nonmilking regions also have high incidences of intolerance. Within the areas of milking in Africa and Europe, moreover, the known group differences in tolerance are found to be in accord with the hypothesis. Then, that the hypothesis may further be confirmed, specific additional research efforts are suggested.
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TL;DR: It is estimated that strong selection occurred within the past 5,000-10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection the authors observe are among the strongest yet seen for any gene in the genome.
Abstract: In most human populations, the ability to digest lactose contained in milk usually disappears in childhood, but in European-derived populations, lactase activity frequently persists into adulthood (Scrimshaw and Murray 1988). It has been suggested (Cavalli-Sforza 1973; Hollox et al. 2001; Enattah et al. 2002; Poulter et al. 2003) that a selective advantage based on additional nutrition from dairy explains these genetically determined population differences (Simoons 1970; Kretchmer 1971; Scrimshaw and Murray 1988; Enattah et al. 2002), but formal population-genetics–based evidence of selection has not yet been provided. To assess the population-genetics evidence for selection, we typed 101 single-nucleotide polymorphisms covering 3.2 Mb around the lactase gene. In northern European–derived populations, two alleles that are tightly associated with lactase persistence (Enattah et al. 2002) uniquely mark a common (∼77%) haplotype that extends largely undisrupted for >1 Mb. We provide two new lines of genetic evidence that this long, common haplotype arose rapidly due to recent selection: (1) by use of the traditional FST measure and a novel test based on pexcess, we demonstrate large frequency differences among populations for the persistence-associated markers and for flanking markers throughout the haplotype, and (2) we show that the haplotype is unusually long, given its high frequency—a hallmark of recent selection. We estimate that strong selection occurred within the past 5,000–10,000 years, consistent with an advantage to lactase persistence in the setting of dairy farming; the signals of selection we observe are among the strongest yet seen for any gene in the genome.
1,015 citations
TL;DR: The considerable potential for cross-disciplinary exchange is highlighted to provide novel insights into how culture has shaped the human genome, supported by recent analyses of human genetic variation, which reveal that hundreds of genes have been subject to recent positive selection.
Abstract: Researchers from diverse backgrounds are converging on the view that human evolution has been shaped by gene-culture interactions. Theoretical biologists have used population genetic models to demonstrate that cultural processes can have a profound effect on human evolution, and anthropologists are investigating cultural practices that modify current selection. These findings are supported by recent analyses of human genetic variation, which reveal that hundreds of genes have been subject to recent positive selection, often in response to human activities. Here, we collate these data, highlighting the considerable potential for cross-disciplinary exchange to provide novel insights into how culture has shaped the human genome.
696 citations
TL;DR: It is inferred that the −13,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe.
Abstract: Lactase persistence (LP) is common among people of European ancestry, but with the exception of some African, Middle Eastern and southern Asian groups, is rare or absent elsewhere in the world. Lactase gene haplotype conservation around a polymorphism strongly associated with LP in Europeans (213,910 C/T) indicates that the derived allele is recent in origin and has been subject to strong positive selection. Furthermore, ancient DNA work has shown that the 213,910*T (derived) allele was very rare or absent in early Neolithic central Europeans. It is unlikely that LP would provide a selective advantage without a supply of fresh milk, and this has lead to a gene-culture coevolutionary model where lactase persistence is only favoured in cultures practicing dairying, and dairying is more favoured in lactase persistent populations. We have developed a flexible demic computer simulation model to explore the spread of lactase persistence, dairying, other subsistence practices and unlinked genetic markers in Europe and western Asia’s geographic space. Using data on 213,910*T allele frequency and farming arrival dates across Europe, and approximate Bayesian computation to estimate parameters of interest, we infer that the 213,910*T allele first underwent selection among dairying farmers around 7,500 years ago in a region between the central Balkans and central Europe, possibly in association with the dissemination of the Neolithic Linearbandkeramik culture over Central Europe. Furthermore, our results suggest that natural selection favouring a lactase persistence allele was not higher in northern latitudes through an increased requirement for dietary vitamin D. Our results provide a coherent and spatially explicit picture of the coevolution of lactase persistence and dairying in Europe.
528 citations
TL;DR: The recent availability of genome-scale genotyping data has led to the identification of regions of the human genome that seem to have been targeted by selection, and these findings have increased the understanding of the evolutionary forces that affect thehuman genome, augmented the knowledge of gene function and promise to increase theUnderstanding of the genetic basis of disease.
Abstract: The recent availability of genome-scale genotyping data has led to the identification of regions of the human genome that seem to have been targeted by selection. These findings have increased our understanding of the evolutionary forces that affect the human genome, have augmented our knowledge of gene function and promise to increase our understanding of the genetic basis of disease. However, inferences of selection are challenged by several confounding factors, especially the complex demographic history of human populations, and concordance between studies is variable. Although such studies will always be associated with some uncertainty, steps can be taken to minimize the effects of confounding factors and improve our interpretation of their findings.
486 citations
TL;DR: A large number of people in the world have hypolactasia, but not everyone has lactose intolerance, as several nutritional and genetic factors influence tolerance.
Abstract: Summary
Background Approximately 70% of the world population has hypolactasia, which often remains undiagnosed and has the potential to cause some morbidity. However, not everyone has lactose intolerance, as several nutritional and genetic factors influence tolerance.
Aims To review current clinical practice and identify published literature on the management of lactose intolerance.
Methods PubMed was searched using the terms lactose, lactase and diet to find original research and reviews. Relevant articles and clinical experience provided the basis for this review.
Results Lactose is found only in mammalian milk and is hydrolysed by lactase in the small intestine. The lactase gene has recently been identified. ‘Wild-type’ is characterized by lactase nonpersistence, often leading to lactose intolerance. Two genetic polymorphisms responsible for persistence have been identified, with their distribution concentrated in north Europeans. Symptoms of lactose intolerance include abdominal pain, bloating, flatulence and diarrhoea. Diagnosis is most commonly by the lactose hydrogen breath test. However, most people with hypolactasia, if given appropriate advice, can tolerate some lactose-containing foods without symptoms.
Conclusion In clinical practice, some people with lactose intolerance can consume milk and dairy foods without developing symptoms, whereas others will need lactose restriction.
467 citations
References
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315 citations
TL;DR: The hypothesis that s-galactosidase in the fetal intestine is induced by circulating lactose is not supported by the evidence presented.
238 citations
TL;DR: The data strongly favor a genetic etiology for the isolated lactase deficiencies seen so commonly in adults, particularly in Negroes, in contrast to only one of 20 whites.
Abstract: An incidence survey of milk intolerance and lactase deficiency was conducted in 40 healthy nonpatient volunteers. There were 20 Negroes and 20 whites. Nineteen of the 20 Negro subjects and two of the 20 white subjects gave a history of milk intolerance. The majority had noted the onset during or after adolescence. Lactose intolerance occurred in 20 of the 21 milk-intolerant subjects; 18 of the 20 were Negro. There was also a prominent racial difference in the incidence of low levels of intestinal lactase activity. Deficient levels were observed in 70% of the 20 Negroes in contrast to only one of 20 whites. These data strongly favor a genetic etiology for the isolated lactase deficiencies seen so commonly in adults.
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