Microsatellite variation and evolution of human lactase persistence
Microsatellite variation and evolution of human lactase persistence
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DOI：
10.1007/s00439-005-1322-z
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发表时间：
2005-08-01
期刊：
影响因子：
5.3
通讯作者：
Rocha, J
中科院分区：
文献类型：
--
作者：
Coelho, M;Luiselli, D;Rocha, J
利用来自葡萄牙、意大利、喀麦隆、圣多美和莫桑比克的794条染色体上的4个快速进化的微卫星基因座，对两个与人乳糖酶持久性相关的单核苷酸多态(SNPs)(-13910 C/T和-22018 G/A)所定义的家系内的单倍型多样性水平进行了评估。基于等位基因内微卫星变异的年龄估计表明，与乳糖酶持久性更密切相关的-13910*T等位基因起源于新石器时代之前的欧亚大陆和非洲以外的现代人出现之后。我们通过使用基于等位基因频率和等位基因内变异水平之间的一致性的中性测试，在来自南欧(葡萄牙和意大利)和非洲(富尔贝)的地理和进化遥远的人群中检测到-13910*T变体的中立性显著偏离中性。这一结果支持选择在乳糖酶持久性进化中的作用，排除了重组抑制和种群历史可能产生的混杂效应。对-13910和-22018位点变异的现有证据的重新评估表明，乳糖酶的持久性可能起源于欧洲和非洲大部分地区的不同突变，即使13910*T不是原因等位基因，这表明选择压力可能促进了该性状的收敛进化。我们的研究表明，有限数量的微卫星座位可能提供足够的分辨率来重建乳糖酶持久性进化历史的关键方面，为基于大量SNPs的方法提供了一种替代方案。
The levels of haplotype diversity within the lineages defined by two single-nucleotide polymorphisms (SNPs) (-13910 C/T and -22018 G/A) associated with human lactase persistence were assessed with four fast-evolving microsatellite loci in 794 chromosomes from Portugal, Italy, Fulbe from Cameroon, Sao Tome and Mozambique. Age estimates based on the intraallelic microsatellite variation indicate that the -13910*T allele, which is more tightly associated with lactase persistence, originated in Eurasia before the Neolithic and after the emergence of modern humans outside Africa. We detected significant departures from neutrality for the -13910*T variant in geographically and evolutionary distant populations from southern Europe (Portuguese and Italians) and Africa (Fulbe) by using a neutrality test based on the congruence between the frequency of the allele and the levels of intraallelic variability measured by the number of mutations in adjacent microsatellites. This result supports the role of selection in the evolution of lactase persistence, ruling out possible confounding effects from recombination suppression and population history. Reevaluation of the available evidence on variation of the -13910 and -22018 loci indicates that lactase persistence probably originated from different mutations in Europe and most of Africa, even if 13910*T is not the causal allele, suggesting that selective pressure could have promoted the convergent evolution of the trait. Our study shows that a limited number of microsatellite loci may provide sufficient resolution to reconstruct key aspects of the evolutionary history of lactase persistence, providing an alternative to approaches based on large numbers of SNPs.