Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 37235, USA.
Department of Biological Sciences, Vanderbilt University, Nashville, TN, 37235, USA.
Nat Commun. 2021 Jul 22;12(1):4481. doi: 10.1038/s41467-021-24582-y.
Eurasians have ~2% Neanderthal ancestry, but we lack a comprehensive understanding of the genome-wide influence of Neanderthal introgression on modern human diseases and traits. Here, we quantify the contribution of introgressed alleles to the heritability of more than 400 diverse traits. We show that genomic regions in which detectable Neanderthal ancestry remains are depleted of heritability for all traits considered, except those related to skin and hair. Introgressed variants themselves are also depleted for contributions to the heritability of most traits. However, introgressed variants shared across multiple Neanderthal populations are enriched for heritability and have consistent directions of effect on several traits with potential relevance to human adaptation to non-African environments, including hair and skin traits, autoimmunity, chronotype, bone density, lung capacity, and menopause age. Integrating our results, we propose a model in which selection against introgressed functional variation was the dominant trend (especially for cognitive traits); however, for a few traits, introgressed variants provided beneficial variation via uni-directional (e.g., lightening skin color) or bi-directional (e.g., modulating immune response) effects.
欧亚人有大约 2%的尼安德特人血统，但我们对尼安德特人基因渗入对现代人类疾病和特征的全基因组影响仍缺乏全面的了解。在这里，我们量化了基因渗入等位基因对 400 多种不同特征的遗传力的贡献。我们发现，在可检测到尼安德特人血统的基因组区域中，除了与皮肤和头发有关的特征外，所有特征的遗传力都明显降低。可检测到的基因渗入变体本身对大多数特征的遗传力贡献也明显减少。然而，在多个尼安德特人群中共享的基因渗入变体在遗传力方面更加丰富，并且在几个与人类对非非洲环境的适应有关的特征（包括毛发和皮肤特征、自身免疫、生物钟、骨密度、肺活量和绝经年龄）上具有一致的影响方向。综合我们的结果，我们提出了一个模型，即对基因渗入功能变异的选择是主要趋势（尤其是对认知特征）；然而，对于一些特征，基因渗入变体通过单向（例如，肤色变浅）或双向（例如，调节免疫反应）效应提供了有益的变异。
