Dataset Information

Stronger signal of recent selection for lactase persistence in Maasai than in Europeans.

ABSTRACT: Continued ability to digest lactose after weaning provides a possible selective advantage to individuals who have access to milk as a food source. The lactase persistence (LP) phenotype exists at varying frequencies in different populations and SNPs that modulate the regulation of the LCT gene have been identified in many of these populations. Very strong positive selection for LP has been illustrated for a single SNP (rs4988235) in northwestern European populations, which has become a textbook example of the effect of recent selective sweeps on genetic variation and linkage disequilibrium. In this study, we employed two different methods to detect signatures of positive selection in an East African pastoralist population in the HapMap collection, the Maasai from Kenya, and compared results with other HapMap populations. We found that signatures of recent selection coinciding with the LCT gene are the strongest across the genome in the Maasai population. Furthermore, the genome-wide signal of recent positive selection on haplotypic variation and population differentiation around the LCT gene is greater in the Maasai than in the CEU population (northwestern European descent), possibly due to stronger selection pressure, but it could also be an indication of more recent selection in Maasai compared with the Central European group or more efficient selection in the Maasai due to less genetic drift for their larger effective population size. This signal of recent selection is driven by a putative East African LP haplotype that is different from the haplotype that contributes to the LP phenotype in northwestern Europe.

SUBMITTER: Schlebusch CM

PROVIDER: S-EPMC3641376 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Stronger signal of recent selection for lactase persistence in Maasai than in Europeans.

Schlebusch Carina M CM Sjödin Per P Skoglund Pontus P Jakobsson Mattias M

European journal of human genetics : EJHG 20120905 5

Continued ability to digest lactose after weaning provides a possible selective advantage to individuals who have access to milk as a food source. The lactase persistence (LP) phenotype exists at varying frequencies in different populations and SNPs that modulate the regulation of the LCT gene have been identified in many of these populations. Very strong positive selection for LP has been illustrated for a single SNP (rs4988235) in northwestern European populations, which has become a textbook ...[more]

PMID: 22948027

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Project description:The Maasai are a pastoral people in Kenya and Tanzania, whose traditional diet of milk, blood and meat is rich in lactose, fat and cholesterol. In spite of this, they have low levels of blood cholesterol, and seldom suffer from gallstones or cardiac diseases. Field studies in the 1970s suggested that the Maasai have a genetic adaptation for cholesterol homeostasis. Analysis of HapMap 3 data using Fixation Index (Fst) and two metrics of haplotype diversity: the integrated Haplotype Score (iHS) and the Cross Population Extended Haplotype Homozygosity (XP-EHH), identified genomic regions and single nucleotide polymorphisms (SNPs) as strong candidates for recent selection for lactase persistence and cholesterol regulation in 143-156 founder individuals from the Maasai population in Kinyawa, Kenya (MKK). The non-synonmous SNP with the highest genome-wide Fst was the TC polymorphism at rs2241883 in Fatty Acid Binding Protein 1(FABP1), known to reduce low density lipoprotein and tri-glyceride levels in Europeans. The strongest signal identified by all three metrics was a 1.7 Mb region on Chr2q21. This region contains the genes LCT (Lactase) and MCM6 (Minichromosome Maintenance Complex Component) involved in lactase persistence, and the gene Rab3GAP1 (Rab3 GTPase-activating Protein Catalytic Subunit), which contains polymorphisms associated with total cholesterol levels in a genome-wide association study of >100,000 individuals of European ancestry. Sanger sequencing of DNA from six MKK samples showed that the GC-14010 polymorphism in the MCM6 gene, known to be associated with lactase persistence in Africans, is segregating in MKK at high frequency (?58%). The Cytochrome P450 Family 3 Subfamily A (CYP3A) cluster of genes, involved in cholesterol metabolism, was identified by Fst and iHS as candidate loci under selection. Overall, our study identified several specific genomic regions under selection in the Maasai which contain polymorphisms in genes associated with lactase persistence and cholesterol regulation.

Project description:BackgroundThe lactase enzyme allows lactose digestion in fresh milk. Its activity strongly decreases after the weaning phase in most humans, but persists at a high frequency in Europe and some nomadic populations. Two hypotheses are usually proposed to explain the particular distribution of the lactase persistence phenotype. The gene-culture coevolution hypothesis supposes a nutritional advantage of lactose digestion in pastoral populations. The calcium assimilation hypothesis suggests that carriers of the lactase persistence allele(s) (LCT*P) are favoured in high-latitude regions, where sunshine is insufficient to allow accurate vitamin-D synthesis. In this work, we test the validity of these two hypotheses on a large worldwide dataset of lactase persistence frequencies by using several complementary approaches.MethodologyWe first analyse the distribution of lactase persistence in various continents in relation to geographic variation, pastoralism levels, and the genetic patterns observed for other independent polymorphisms. Then we use computer simulations and a large database of archaeological dates for the introduction of domestication to explore the evolution of these frequencies in Europe according to different demographic scenarios and selection intensities.ConclusionsOur results show that gene-culture coevolution is a likely hypothesis in Africa as high LCT*P frequencies are preferentially found in pastoral populations. In Europe, we show that population history played an important role in the diffusion of lactase persistence over the continent. Moreover, selection pressure on lactase persistence has been very high in the North-western part of the continent, by contrast to the South-eastern part where genetic drift alone can explain the observed frequencies. This selection pressure increasing with latitude is highly compatible with the calcium assimilation hypothesis while the gene-culture coevolution hypothesis cannot be ruled out if a positively selected lactase gene was carried at the front of the expansion wave during the Neolithic transition in Europe.

Dataset Information

Stronger signal of recent selection for lactase persistence in Maasai than in Europeans.

Publications

Stronger signal of recent selection for lactase persistence in Maasai than in Europeans.

Similar Datasets

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