Division of General Internal Medicine, Department of Medicine, The Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS One. 2012;7(9):e44926. doi: 10.1371/journal.pone.0044926. Epub 2012 Sep 19.
Long chain polyunsaturated fatty acids (LC-PUFAs) are essential for brain structure, development, and function, and adequate dietary quantities of LC-PUFAs are thought to have been necessary for both brain expansion and the increase in brain complexity observed during modern human evolution. Previous studies conducted in largely European populations suggest that humans have limited capacity to synthesize brain LC-PUFAs such as docosahexaenoic acid (DHA) from plant-based medium chain (MC) PUFAs due to limited desaturase activity. Population-based differences in LC-PUFA levels and their product-to-substrate ratios can, in part, be explained by polymorphisms in the fatty acid desaturase (FADS) gene cluster, which have been associated with increased conversion of MC-PUFAs to LC-PUFAs. Here, we show evidence that these high efficiency converter alleles in the FADS gene cluster were likely driven to near fixation in African populations by positive selection ∼85 kya. We hypothesize that selection at FADS variants, which increase LC-PUFA synthesis from plant-based MC-PUFAs, played an important role in allowing African populations obligatorily tethered to marine sources for LC-PUFAs in isolated geographic regions, to rapidly expand throughout the African continent 60-80 kya.
长链多不饱和脂肪酸（LC-PUFAs）对大脑结构、发育和功能至关重要，足够数量的 LC-PUFAs 被认为是大脑扩张和现代人类进化过程中观察到的大脑复杂性增加所必需的。之前在主要欧洲人群中进行的研究表明，由于脱饱和酶活性有限，人类从植物源中链（MC）多不饱和脂肪酸合成大脑 LC-PUFAs（如二十二碳六烯酸，DHA）的能力有限。LC-PUFA 水平及其产物与底物比值的人群差异部分可以用脂肪酸去饱和酶（FADS）基因簇中的多态性来解释，这些多态性与 MC-PUFAs 向 LC-PUFAs 的转化率增加有关。在这里，我们提供的证据表明，这些 FADS 基因簇中的高效转化等位基因可能是由于约 85 千年前的正选择而在非洲人群中接近固定的。我们假设，FADS 变体的选择，这些变体增加了植物源 MC-PUFAs 向 LC-PUFAs 的合成，在允许非洲人群强制性地依赖海洋来源的 LC-PUFAs 于孤立的地理区域中，在 60-80 千年前迅速扩展到整个非洲大陆的过程中发挥了重要作用。
