Hollox E J, Poulter M, Zvarik M, Ferak V, Krause A, Jenkins T, Saha N, Kozlov A I, Swallow D M
MRC Human Biochemical Genetics Unit, Galton Laboratory, Department of Biology, University College London, London NW1 2HE, United Kingdom.
Am J Hum Genet. 2001 Jan;68(1):160-172. doi: 10.1086/316924. Epub 2000 Nov 28.
Lactase persistence, the genetic trait in which intestinal lactase activity persists at childhood levels into adulthood, varies in frequency in different human populations, being most frequent in northern Europeans and certain African and Arabian nomadic tribes, who have a history of drinking fresh milk. Selection is likely to have played an important role in establishing these different frequencies since the development of agricultural pastoralism approximately 9,000 years ago. We have previously shown that the element responsible for the lactase persistence/nonpersistence polymorphism in humans is cis-acting to the lactase gene and that lactase persistence is associated, in Europeans, with the most common 70-kb lactase haplotype, A. We report here a study of the 11-site haplotype in 1,338 chromosomes from 11 populations that differ in lactase persistence frequency. Our data show that haplotype diversity was generated both by point mutations and recombinations. The four globally common haplotypes (A, B, C, and U) are not closely related and have different distributions; the A haplotype is at high frequencies only in northern Europeans, where lactase persistence is common; and the U haplotype is virtually absent from Indo-European populations. Much more diversity is seen in sub-Saharan Africans than in non-Africans, consistent with an "Out of Africa" model for peopling of the Old World. Analysis of recent recombinant haplotypes by allele-specific PCR, along with deduction of the root haplotype from chimpanzee sequence, allowed construction of a haplotype network that assisted in evaluation of the relative roles of drift and selection in establishing the haplotype frequencies in the different populations. We suggest that genetic drift was important in shaping the general pattern of non-African haplotype diversity, with recent directional selection in northern Europeans for the haplotype associated with lactase persistence.
乳糖酶持久性是一种遗传特征，即肠道乳糖酶活性在儿童期水平持续至成年期，在不同人类群体中的出现频率有所不同，在北欧人以及某些有饮用新鲜牛奶历史的非洲和阿拉伯游牧部落中最为常见。自大约9000年前农业畜牧主义发展以来，选择可能在建立这些不同频率方面发挥了重要作用。我们之前已经表明，人类中负责乳糖酶持久性/非持久性多态性的元件对乳糖酶基因具有顺式作用，并且在欧洲人中，乳糖酶持久性与最常见的70kb乳糖酶单倍型A相关。我们在此报告了一项对来自11个群体的1338条染色体上的11位点单倍型的研究，这些群体的乳糖酶持久性频率不同。我们的数据表明，单倍型多样性是由点突变和重组产生的。四种全球常见的单倍型（A、B、C和U）没有密切关系且分布不同；A单倍型仅在北欧人（乳糖酶持久性常见）中高频出现；U单倍型在印欧人群体中几乎不存在。撒哈拉以南非洲人比非非洲人表现出更多的多样性，这与旧世界人口起源的“走出非洲”模型一致。通过等位基因特异性PCR对近期重组单倍型进行分析，并从黑猩猩序列推导根单倍型，从而构建了一个单倍型网络，有助于评估漂变和选择在不同群体中建立单倍型频率的相对作用。我们认为，遗传漂变在塑造非非洲单倍型多样性的总体模式方面很重要，而近期北欧人对与乳糖酶持久性相关的单倍型进行了定向选择。
