Natural selection has contributed to functional immune response differences between human hunter-gatherers and agriculturalists

The shift from a hunter-gatherer (HG) to an agricultural (AG) 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 impacted 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 (PBMCs) to bacterial and viral stimuli between the Batwa, a rainforest hunter-gatherer, and the Bakiga, an agriculturalist population from Central Africa. We observed increased divergence between hunter-gatherers and farmers in the transcriptional response to viruses compared to 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. Unexpectedly, we found stronger signatures of recent natural selection in the rainforest hunter-gatherers, which argues against the popularized notion that shifts in pathogen exposure due to the advent of agriculture imposed radically heightened selective pressures in agriculturalist populations. Gene expression profiles of peripheral blood mononuclear cells (PBMCs) that were simulated with the viral ligand Gardiquimod (GARD), the bacterial ligand lippopolysacharide (LPS), or a match un-stimulated control (CTL)

从狩猎采集（hunter-gatherer, HG）向农业（agricultural, AG）生计模式的转变，被认为与人类群体中病原体负荷与多样性的深刻变化紧密相关。然而，农业的出现对人类免疫系统演化的影响程度，目前仍不明确。本研究对两类人群的外周血单个核细胞（peripheral blood mononuclear cells, PBMCs）在细菌与病毒刺激下的转录反应差异进行比较分析：一类为雨林狩猎采集人群巴特瓦人（Batwa），另一类为来自中非的农业人群巴基加人（Bakiga）。研究发现，相较于细菌刺激，狩猎采集人群与农业人群在病毒刺激下的转录反应差异更为显著。我们证实，这类转录差异中有显著比例受到遗传调控，且正向自然选择参与塑造了人群间免疫调控的差异。出乎意料的是，我们在雨林狩猎采集人群中检测到更强的近期自然选择信号，这与广为流传的观点相悖——该观点认为农业出现带来的病原体暴露变化，给农业人群带来了大幅升高的选择压力。本研究的实验体系为：对外周血单个核细胞（PBMCs）分别施加病毒配体Gardiquimod（GARD）、细菌配体脂多糖（lipopolysaccharide, LPS，原文存在拼写笔误，原拼写为lippopolysacharide）处理，以及设置匹配型未刺激对照（CTL），以获取对应基因表达谱。