Convergent adaptation of human lactase persistence in Africa and Europe

Tishkoff, Sarah A.; Reed, Floyd A.; Ranciaro, Alessia; Voight, Benjamin F.; Babbitt, Courtney C.; Silverman, Jesse S.; Powell, Kweli; Mortensen, Holly M.; Hirbo, Jibril; Osman, Maha M.; Ibrahim, Muntaser E.; Omar, Sabah A.; Lema, Godfrey; Nyambo, Thomas; Ghori, Jilur; Bumpstead, Suzannah; Pritchard, Jonathan K.; Wray, Gregory A.; Deloukas, Panos

doi:10.1038/ng1946

Cited by 1,323 publications

(1,207 citation statements)

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“…5 In other populations, different polymorphisms in the LCT promoter have been also shown to be associated with lactase persistence. 6 Several studies support the perspective that these differences in lactase persistence between populations can be ascribed to processes of positive selection. 1,2 Indeed, it has been suggested that the frequency of lactase persistence has increased in several populations as cattle domestication and dairy consumption was introduced in Europe.…”

Section: Introductionmentioning

confidence: 93%

Low prevalence of lactase persistence in Neolithic South-West Europe

et al. 2012

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The ability of humans to digest the milk component lactose after weaning requires persistent production of the lactoseconverting enzyme lactase. Genetic variation in the promoter of the lactase gene (LCT) is known to be associated with lactase production and is therefore a genetic determinant for either lactase deficiency or lactase persistence during adulthood. Large differences in this genetic trait exist between populations in Africa and the Middle-East on the one hand, and European populations on the other; this is thought to be due to evolutionary pressures exerted by consumption of dairy products in Neolithic populations in Europe. In this study, we have investigated lactase persistence of 26 out of 46 individuals from Late Neolithic through analysis of ancient South-West European DNA samples, obtained from two burials in the Basque Country originating from 5000 to 4500 YBP. This investigation revealed that these populations had an average frequency of lactase persistence of 27%, much lower than in the modern Basque population, which is compatible with the concept that Neolithic and post-Neolithic evolutionary pressures by cattle domestication and consumption of dairy products led to high lactase persistence in Southern European populations. Given the heterogeneity in the frequency of the lactase persistence allele in ancient Europe, we suggest that in Southern Europe the selective advantage of lactose assimilation in adulthood most likely took place from standing population variation, after cattle domestication, at a post-Neolithic time when fresh milk consumption was already fully adopted as a consequence of a cultural influence.

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Section: Introductionmentioning

confidence: 93%

Low prevalence of lactase persistence in Neolithic South-West Europe

et al. 2012

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“…This region has been implicated as the genetic basis for lactase persistence in several African populations, including some from Kenya, and has evidence of having undergone recent, strong positive selection. 30 The first region on chromosome 6 (29.77-30.17 Mb) is coincident with the HLA class I region, a portion of the genome well known as being under strong selective pressure due to its importance in immune system function. 31 The second highest peak on chromosome 6 (130.61-130.81 Mb) contains only two known genes, KIAA1913 and SAMD3.…”

Section: Resultsmentioning

confidence: 99%

Using identity by descent estimation with dense genotype data to detect positive selection

Han

Abney

2012

Eur J Hum Genet

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Identification of genomic loci and segments that are identical by descent (IBD) allows inference on problems such as relatedness detection, IBD disease mapping, heritability estimation and detection of recent or ongoing positive selection. Here, employing a novel statistical method, we use IBD to find signals of selection in the Maasai from Kinyawa, Kenya (MKK). In doing so, we demonstrate the advantage of statistical tools that can probabilistically estimate IBD sharing without having to thin genotype data because of linkage disequilibrium (LD), and that allow for both inbreeding and more than one allele to be shared IBD. We use our novel method, GIBDLD, to estimate IBD sharing between all pairs of individuals at all genotyped SNPs in the MKK, and, by looking for genomic regions showing excess IBD sharing in unrelated pairs, find loci that are known to have undergone recent selection (eg, the LCT gene and the HLA region) as well as many novel loci. Intriguingly, those loci that show the highest amount of excess IBD, with the exception of HLA, also show a substantial number of unrelated pairs sharing all four of their alleles IBD. In contrast to other IBD detection methods, GIBDLD provides accurate probabilistic estimates at each locus for all nine possible IBD sharing states between a pair of individuals, thus allowing for consanguinity, while also modeling LD, thus removing the need to thin SNPs. These characteristics will prove valuable for those doing genetic studies, and estimating IBD, in the wide variety of human populations. European Journal of Human Genetics (2013) 21, 205-211; doi:10.1038/ejhg.2012.148; published online 11 July 2012Keywords: identity by descent; natural selection; consanguinity; cryptic relatedness; relationship inference; SNPs INTRODUCTIONThe ability to discover recent positive selection in the human genome is one compelling reason to estimate identity by descent (IBD) in a cohort of largely unrelated individuals. In particular, IBD can be used to find selection on standing variation, a situation where many methods used for detecting selection may not perform well. 1 Additionally, other genetic questions can be well addressed by estimating IBD within a set of individuals. These include, detection of unknown or mistaken relationships, 2-6 estimation of heritability and genomic partitioning of genetic variance, 7,8 and mapping by the identification of shared segments. 9-13 IBD, however, is not directly observed but must be inferred from the available data. Traditionally, the combination of a pedigree with genotype data enabled the efficient computation of IBD using either 'peeling' 14 or hidden Markov models (HMMs). [15][16][17] More recently, however, the large amounts of information made available from high density SNP genotyping arrays has enabled estimation of IBD even for very distantly related pairs of individuals (ie, 410 generations) in the absence of pedigree information. This additional data, however, also presents the difficulty of accommodating the linkage disequilibrium (LD...

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“…Finally, we have only tested one of several LP alleles. Other LP alleles have arisen independently in other groups (Imtiaz et al 2007;Ingram et al 2007Ingram et al , 2009Tishkoff et al 2007;Büning et al 2004;Itan et al 2010). It is possible that not all individuals who lack the particular LP allele tested are in fact lactose intolerant.…”

Section: Discussionmentioning

confidence: 99%

“…There is strong evidence that the selective pressures that led to the LP allele being common in these geographic regions originated from the dairying practices begun by early European and West Asian farmers \10,000 years ago (Bersaglieri et al 2004;Scrimshaw and Murray 1988). This and other lactase persistence alleles found in African and other populations (Imtiaz et al 2007;Ingram et al 2007;Tishkoff et al 2007) likely conferred a selective advantage by providing an additional source of energy and preventing the malabsorption of dairy nutrients associated with lactose (Debongnie et al 1979).…”

Section: Introductionmentioning

confidence: 99%

Associations of the lactase persistence allele and lactose intake with body composition among multiethnic children

et al. 2013

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Childhood obesity is a worldwide health concern with a multifaceted and sometimes confounding etiology. Dairy products have been implicated as both proand anti-obesogenic, perhaps due to the confounding relationship between dairy, lactose consumption, and potential genetic predisposition. We aimed to understand how lactase persistence influenced obesity-related traits by observing the relationships among lactose consumption, a single nucleotide polymorphism (SNP) near the lactase (LCT) gene and body composition parameters in a sample of multiethnic children (n = 296, 7-12 years old). We hypothesized that individuals with the lactase persistence (LP) allele of the LCT SNP (rs4988235) would exhibit a greater degree of adiposity and that this relationship would be mediated by lactose consumption. Body composition variables were measured using dual X-ray absorptiometry and a registered dietitian assessed dietary intake of lactose. Statistical models were adjusted for sex, age, pubertal stage, ethnic group, genetic admixture, socio-economic status, and total energy intake. Our findings indicate a positive, significant association between the LP allele and body mass index (p = 0.034), fat mass index (FMI) (p = 0.043), and waist circumference (p = 0.008), with associations being stronger in males than in females. Our results also reveal that lactose consumption is positively and nearly significantly associated with FMI.

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Convergent adaptation of human lactase persistence in Africa and Europe

Cited by 1,323 publications

References 45 publications

Low prevalence of lactase persistence in Neolithic South-West Europe

Low prevalence of lactase persistence in Neolithic South-West Europe

Using identity by descent estimation with dense genotype data to detect positive selection

Associations of the lactase persistence allele and lactose intake with body composition among multiethnic children

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