Detecting past and ongoing natural selection among ethnically Tibetan women at high altitude in Nepal

Adaptive evolution in humans has rarely been characterized for its whole set of components, i.e. selective pressure, adaptive phenotype, beneficial alleles and realized fitness differential. We combined approaches for detecting selective sweeps and polygenic adaptations and for mapping the genetic bases of physiological and fertility phenotypes in approximately 1000 indigenous ethnically Tibetan women from Nepal, adapted to high altitude. We performed genome-wide association analysis and tests for polygenic adaptations which showed evidence of positive selection for alleles associated with more pregnancies and live births and evidence of negative selection for those associated with higher offspring mortality. Lower hemoglobin level did not show clear evidence for polygenic adaptation, despite its strong association with an EPAS1 haplotype carrying selective sweep signals.

人类适应性演化的完整组分——即选择压力、适应性表型、有益等位基因以及已实现的适合度差异——迄今极少得到全面解析。本研究以约1000名世居尼泊尔高原的藏族土著女性为研究对象，整合了选择性清除（selective sweep）检测、多基因适应性演化（polygenic adaptation）检测以及生理与生育表型遗传基础定位的相关方法。本研究开展了全基因组关联分析与多基因适应性演化检测，结果显示：与更高妊娠次数及活产数相关的等位基因呈现正选择信号，而与更高后代死亡率相关的等位基因则呈现负选择信号。尽管较低血红蛋白水平与携带选择性清除信号的EPAS1单倍型存在强关联，但并未呈现明确的多基因适应性演化证据。