Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Department of Genetics, CHU Sainte-Justine Research Center, Montreal, Quebec, Canada.
Nat Ecol Evol. 2019 Aug;3(8):1253-1264. doi: 10.1038/s41559-019-0947-6. Epub 2019 Jul 29.
The shift from a hunter-gatherer to an agricultural mode of subsistence is believed to have been associated with profound changes in the burden and diversity of pathogens across human populations. Yet, the extent to which the advent of agriculture affected the evolution of the human immune system remains unknown. Here we present a comparative study of variation in the transcriptional responses of peripheral blood mononuclear cells to bacterial and viral stimuli between Batwa rainforest hunter-gatherers and Bakiga agriculturalists from Uganda. We observed increased divergence between hunter-gatherers and agriculturalists in the early transcriptional response to viruses compared with that for bacterial stimuli. We demonstrate that a significant fraction of these transcriptional differences are under genetic control and we show that positive natural selection has helped to shape population differences in immune regulation. Across the set of genetic variants underlying inter-population immune-response differences, however, the signatures of positive selection were disproportionately observed in the rainforest hunter-gatherers. This result is counter to expectations on the basis of the popularized notion that shifts in pathogen exposure due to the advent of agriculture imposed radically heightened selective pressures in agriculturalist populations.
从狩猎采集到农业的生活方式转变被认为与人类群体中病原体的负担和多样性发生了深刻的变化有关。然而，农业的出现对人类免疫系统的进化产生了何种影响仍不得而知。在这里，我们对来自乌干达的雨林狩猎采集者巴图阿人和农业巴基加人外周血单个核细胞对细菌和病毒刺激的转录反应的变异性进行了比较研究。我们观察到，与细菌刺激相比，狩猎采集者和农业者在病毒的早期转录反应中表现出更大的差异。我们证明，这些转录差异的很大一部分受遗传控制，并且表明自然选择有助于塑造免疫调节的人群差异。在引起人群间免疫反应差异的遗传变异集中，然而，在雨林狩猎采集者中观察到正选择的特征不成比例。这一结果与由于农业的出现而导致病原体暴露的转变对农业人口施加了激进的选择压力的流行观点相悖。
