Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture
Independent introduction of two lactase-persistence alleles into human populations reflects different history of adaptation to milk culture
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DOI：
10.1016/j.ajhg.2007.09.012
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发表时间：
2008-01-01
影响因子：
9.8
通讯作者：
Peltonen, Leena
中科院分区：
文献类型：
--
作者：
Enattah, Nabil Sabri;Jensen, Tine G. K.;Peltonen, Leena
位于乳糖酶（LCT）基因增强子元件的T-13910变异与欧亚人群中的乳糖酶持久性（LP）完全相关，而该变异在撒哈拉以南非洲人群中几乎不存在，显示出LP的高患病率。在这里，我们报告了在沙特人中发现的两种新的突变，这两种突变也以LP的高患病率而闻名。我们证实了欧洲T-13910的缺失，并建立了两个新的突变作为复合等位基因：-13910增强子区域内的T/G（-13915）和MCM 6基因外显子17中的同义SNP T/C-3712，距离LCT基因-3712 bp。复合等位基因在中东人群中的流行率很高。我们的体外功能分析表明，两个SNP的复合等位基因，位于相隔10 kb，所需的增强子效应，最有可能通过肝核因子1 α（HNF 1 α）的结合介导。T-13910和复合等位基因对LP表型的选择系数都很高，接近0.04。欧洲T-13910和早期鉴定的东非G（-13907）LP等位基因具有相同的祖先背景，很可能具有相同的历史，可能与相同的牛驯化事件有关。与此相反，复合阿拉伯等位基因表现出不同的，高度发散的祖先单倍型，这表明这两个主要的全球LP等位基因已经独立出现，后者可能是在骆驼奶消费的反应。这些结果支持收敛进化的LP在不同的人群中，最有可能反映不同的历史适应牛奶文化。
The T-13910 variant located in the enhancer element of the lactase (LCT) gene correlates perfectly with lactase persistence (LP) in Eurasian populations whereas the variant is almost nonexistent among Sub-Saharan African populations, showing high prevalence of LP. Here, we report identification of two new mutations among Saudis, also known for the high prevalence of LP. We confirmed the absence of the European T-13910 and established two new mutations found as a compound allete: T/G(-13915) within the -13910 enhancer region and a synonymous SNP in the exon 17 of the MCM6 gene T/C-3712, -3712 bp from the LCT gene. The compound allele is driven to a high prevalence among Middle East population(s). Our functional analyses in vitro showed that both SNPs of the compound allele, located 10 kb apart, are required for the enhancer effect, most probably mediated through the binding of the hepatic nuclear factor 1 alpha (HNF1 alpha). High selection coefficient (s) similar to 0.04 for LP phenotype was found for both T-13910 and the compound allele. The European T-13910 and the earlier identified East African G(-13907) LP allele share the same ancestral background and most likely the same history, probably related to the same cattle domestication event. In contrast, the compound Arab allele shows a different, highly divergent ancestral haplotype, suggesting that these two major global LP alleles have arisen independently, the latter perhaps in response to camel milk consumption. These results support the convergent evolution of the LP in diverse populations, most probably reflecting different histories of adaptation to milk culture.