Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853, USA.
Department of Anthropology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nat Ecol Evol. 2017 May 26;1:167. doi: 10.1038/s41559-017-0167.
Fatty acid desaturase (FADS) genes encode rate-limiting enzymes for the biosynthesis of omega-6 and omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). This biosynthesis is essential for individuals subsisting on LCPUFA-poor diets (for example, plant-based). Positive selection on FADS genes has been reported in multiple populations, but its cause and pattern in Europeans remain unknown. Here we demonstrate, using ancient and modern DNA, that positive selection acted on the same FADS variants both before and after the advent of farming in Europe, but on opposite (that is, alternative) alleles. Recent selection in farmers also varied geographically, with the strongest signal in southern Europe. These varying selection patterns concur with anthropological evidence of varying diets, and with the association of farming-adaptive alleles with higher FADS1 expression and thus enhanced LCPUFA biosynthesis. Genome-wide association studies reveal that farming-adaptive alleles not only increase LCPUFAs, but also affect other lipid levels and protect against several inflammatory diseases.
脂肪酸去饱和酶（FADS）基因编码ω-6 和 ω-3 长链多不饱和脂肪酸（LCPUFA）生物合成的限速酶。对于依赖 LCPUFA 缺乏饮食（例如，植物性饮食）的个体来说，这种生物合成是必不可少的。在多个人群中已经报道了 FADS 基因的正选择，但在欧洲人中其原因和模式仍不清楚。在这里，我们使用古代和现代 DNA 证明，在农业出现之前和之后，对 FADS 变体的正选择作用于相同的变体，但作用于相反（即替代）等位基因。农民中的近期选择也具有地域性，在南欧的信号最强。这些不同的选择模式与饮食变化的人类学证据以及与与农业适应性等位基因相关的更高的 FADS1 表达和增强的 LCPUFA 生物合成一致。全基因组关联研究表明，农业适应性等位基因不仅增加了 LCPUFAs，还影响了其他脂质水平，并预防了几种炎症性疾病。
