Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection.
Whole-genome sequence analyses of Western Central African Pygmy hunter-gatherers reveal a complex demographic history and identify candidate genes under positive natural selection.
复制标题
DOI：
10.1101/gr.192971.115
复制
发表时间：
2016-03
期刊：
影响因子：
7
通讯作者：
Gutenkunst RN
中科院分区：
文献类型：
--
作者：
Hsieh P;Veeramah KR;Lachance J;Tishkoff SA;Wall JD;Hammer MF;Gutenkunst RN
非洲俾格米人过着流动的狩猎采集生活方式，在表型和基因上都与其他解剖学上的现代人不同，由于他们在中非雨林的独特生活方式，他们可能经历了强大的选择压力。为了确定适应的基因组目标，我们对来自中非共和国的4名比亚卡俾格米人的基因组进行了测序，并将这些数据与来自喀麦隆的3名巴卡俾格米人和9名约鲁巴农民的基因组序列进行了联合分析。为了解释这些群体复杂的人口统计历史，包括隔离和基因流动，我们使用联合等位基因频谱拟合模型，并使用独立的方法验证它们。我们的两个最合适的模型都表明，在9万或15万年前，农民和俾格米人的祖先之间存在着古老的分歧。我们还发现，双向非对称基因流动在统计上比以前提出的从农民到俾格米人的单向基因流动的单一脉冲更好地得到支持。然后，我们应用互补统计来扫描基因组，寻找选择性扫描和多基因选择的证据。我们发现传统的统计异常值方法偏向于在高突变率或低重组率的区域识别候选基因。为了避免这种偏差，我们使用包含人口统计学和重组率和突变率变异的全基因组模拟为候选对象分配了p值。我们发现，与肌肉发育、骨骼合成、免疫、生殖、细胞信号传导和发育以及能量代谢有关的基因和基因集很可能是西非俾格米人或其最近祖先积极自然选择的目标。
African Pygmies practicing a mobile hunter-gatherer lifestyle are phenotypically and genetically diverged from other anatomically modern humans, and they likely experienced strong selective pressures due to their unique lifestyle in the Central African rainforest. To identify genomic targets of adaptation, we sequenced the genomes of four Biaka Pygmies from the Central African Republic and jointly analyzed these data with the genome sequences of three Baka Pygmies from Cameroon and nine Yoruba famers. To account for the complex demographic history of these populations that includes both isolation and gene flow, we fit models using the joint allele frequency spectrum and validated them using independent approaches. Our two best-fit models both suggest ancient divergence between the ancestors of the farmers and Pygmies, 90,000 or 150,000 yr ago. We also find that bidirectional asymmetric gene flow is statistically better supported than a single pulse of unidirectional gene flow from farmers to Pygmies, as previously suggested. We then applied complementary statistics to scan the genome for evidence of selective sweeps and polygenic selection. We found that conventional statistical outlier approaches were biased toward identifying candidates in regions of high mutation or low recombination rate. To avoid this bias, we assigned P-values for candidates using whole-genome simulations incorporating demography and variation in both recombination and mutation rates. We found that genes and gene sets involved in muscle development, bone synthesis, immunity, reproduction, cell signaling and development, and energy metabolism are likely to be targets of positive natural selection in Western African Pygmies or their recent ancestors.