Akey Joshua M
Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
Genome Res. 2009 May;19(5):711-22. doi: 10.1101/gr.086652.108.
Identifying targets of positive selection in humans has, until recently, been frustratingly slow, relying on the analysis of individual candidate genes. Genomics, however, has provided the necessary resources to systematically interrogate the entire genome for signatures of natural selection. To date, 21 genome-wide scans for recent or ongoing positive selection have been performed in humans. A key challenge is to begin synthesizing these newly constructed maps of positive selection into a coherent narrative of human evolutionary history and derive a deeper mechanistic understanding of how natural populations evolve. Here, I chronicle the recent history of the burgeoning field of human population genomics, critically assess genome-wide scans for positive selection in humans, identify important gaps in knowledge, and discuss both short- and long-term strategies for traversing the path from the low-resolution, incomplete, and error-prone maps of selection today to the ultimate goal of a detailed molecular, mechanistic, phenotypic, and population genetics characterization of adaptive alleles.
直到最近，通过分析单个候选基因来确定人类正选择的目标一直进展缓慢，令人沮丧。然而，基因组学提供了必要的资源，能够系统地在整个基因组中探寻自然选择的印记。迄今为止，已对人类进行了21次全基因组范围的近期或正在进行的正选择扫描。一个关键挑战是开始将这些新构建的正选择图谱整合为关于人类进化历史的连贯叙述，并对自然种群如何进化获得更深入的机制理解。在此，我记述了人类群体基因组学这一新兴领域的近期发展历程，批判性地评估人类正选择的全基因组扫描，找出知识上的重要空白，并讨论从如今低分辨率、不完整且容易出错的选择图谱迈向对适应性等位基因进行详细分子、机制、表型和群体遗传学特征描述这一最终目标的短期和长期策略。
