World-wide distributions of lactase persistence alleles and the complex effects of recombination and selection

Abstract

The genetic trait of lactase persistence (LP) is associated with at least five independent functional single nucleotide variants in a regulatory region about 14 kb upstream of the lactase gene [−13910*T (rs4988235), −13907*G (rs41525747), −13915*G (rs41380347), −14009*G (rs869051967) and −14010*C (rs145946881)]. These alleles have been inferred to have spread recently and present-day frequencies have been attributed to positive selection for the ability of adult humans to digest lactose without risk of symptoms of lactose intolerance. One of the inferential approaches used to estimate the level of past selection has been to determine the extent of haplotype homozygosity (EHH) of the sequence surrounding the SNP of interest. We report here new data on the frequencies of the known LP alleles in the ‘Old World’ and their haplotype lineages. We examine and confirm EHH of each of the LP alleles in relation to their distinct lineages, but also show marked EHH for one of the older haplotypes that does not carry any of the five LP alleles. The region of EHH of this (B) haplotype exactly coincides with a region of suppressed recombination that is detectable in families as well as in population data, and the results show how such suppression may have exaggerated haplotype-based measures of past selection.Electronic supplementary materialThe online version of this article (doi:10.1007/s00439-017-1847-y) contains supplementary material, which is available to authorized users.

New insights into Neolithic milk consumption through proteomic analysis of dental calculus

“…It was therefore commonly assumed that increased reliance on dairy products from the Early Neolithic would have driven the selection of LP during subsequent millennia. At least five different allelic variants have been identified as causative of LP globally, suggesting convergent evolution (Tishkoff et al 2007;Jones et al 2015;Liebert et al 2017). Initial investigations of the European LCT gene responsible for LP (C-13910 > T; −13910*T allele (rs4988235)) suggested that selection favouring the LP allele may have begun in the Neolithic in conjunction with the spread of agriculture and increased use of domesticated animal species.…”

Експресія МРНК Галектину-9 При Ожирінні У Дітей З Поліморфізмами Гена Лактази

“…Персистенція лактази, що асоціюється з фе-нотипово схожими генотипами С/Т та Т/Т-13910, успадковується як домінуюча менделівська риса, що виникла близько 10 000 років тому серед пле-мен Північної Європи, що займалися скотарством, та зумовила 100-відсотковий рівень експресії лак-тази протягом дорослого життя [12,16,17]. У наш час максимальна частота зустрічальності лактазної персистенції понад 90 % виявляється саме серед на-селення північноєвропейських країн (Скандинавії та Нідерландів), мінімальна зустрічальність алелі Т-13910 менше ніж 50 % представлена серед насе-лення Південної Європи (Італії та Іспанії).…”

New insights into the molecular basis of lactase non-persistence/persistence: a brief review

“…Positive selection for LP which allows the dietary consumption of animal milk by adult humans without risk of symptoms of lactose intolerance has been attributed to present day frequencies of these alleles (49-52). Population expansion, migration, allele surfing and cultural/environmental processes may also have influenced the distributions of these alleles (49,52).…”