Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage
Evidence that the adaptive allele of the brain size gene microcephalin introgressed into Homo sapiens from an archaic Homo lineage
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DOI：
10.1073/pnas.0606966103
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发表时间：
2006-11-28
影响因子：
11.1
通讯作者：
Lahn, Bruce T.
中科院分区：
文献类型：
--
作者：
Evans, Patrick D.;Mekel-Bobrov, Nitzan;Lahn, Bruce T.
关于现代人的出现及其在全球范围内传播的辩论的中心问题是，古代人的谱系是否对现代人的基因库做出了贡献，更重要的是，这种贡献是否影响了我们物种的进化适应。回答这个问题的一个主要障碍是，由于基因漂移，与古老血统的低水平混合预计不会在现代人的基因库中留下广泛的痕迹。然而，经过强正向选择的基因座提供了一个独特的机会来识别低水平与古老谱系的混合，前提是引入的古老等位基因在正选择下已上升到高频。小脑啡肽基因(MCPH1)在发育过程中调节大脑大小，并在导致智人的谱系中经历了正向选择。在现代人中，该基因座上一组密切相关的单倍型，被称为单倍组ID，从大约37,000年前的单个拷贝上升到异常高的频率(今天全球约有70%)，因为正选择。在这里，我们考察了单倍群D的起源。通过单倍群间发散检验，我们表明单倍群D可能起源于大约110万年前从现代人类分离出来的一个谱系，并在大约3.7万年前引入人类。这一发现支持了现代人和古代人种群混杂的可能性(尼安德特人是其中一种可能性)。此外，它支持了这样一个重要的概念，即通过这样的管理，我们的物种通过获得新的有利等位基因而在进化上受益。该方法可广泛应用于人类基因组或其他物种基因组中其他基因座的渐渗检测。
At the center of the debate on the emergence of modern humans and their spread throughout the globe is the question of whether archaic Homo lineages contributed to the modern human gene pool, and more importantly, whether such contributions impacted the evolutionary adaptation of our species. A major obstacle to answering this question is that low levels of admixture with archaic lineages are not expected to leave extensive traces in the modern human gene pool because of genetic drift. Loci that have undergone strong positive selection, however, offer a unique opportunity to identify low-level admixture with archaic lineages, provided that the introgressed archaic allele has risen to high frequency under positive selection. The gene microcephalin (MCPH1) regulates brain size during development and has experienced positive selection in the lineage leading to Homo sapiens. Within modern humans, a group of closely related haplotypes at this locus, known as haplogroup ID, rose from a single copy approximate to 37,000 years ago and swept to exceptionally high frequency (approximate to 70% worldwide today) because of positive selection. Here, we examine the origin of haplogroup D. By using the interhaplogroup divergence test, we show that haplogroup D likely originated from a lineage separated from modern humans approximate to 1.1 million years ago and introgressed into humans by approximate to 37,000 years ago. This finding supports the possibility of admixture between modern humans and archaic Homo populations (Neanderthals being one possibility). Furthermore, it buttresses the important notion that, through such adminture, our species has benefited evolutionarily by gaining new advantageous alleles. The interhaplogroup divergence test developed here may be broadly applicable to the detection of introgression at other loci in the human genome or in genomes of other species.