The Genetic Basis of Adaptation to Climatic Stress in Siberian Indigenous Populations

我们的物种起源于非洲，随后分散到除南极洲以外的所有其他大陆。在这一分散过程中，人类暴露在与非洲本土截然不同的各种气候中。没有哪个地方的气候条件比西伯利亚北部地区的差异更大。的确，人类是除了日本猕猴之外唯一适应北方环境的灵长类动物。那里的气温在半年以上的时间里都远低于冰点？这表明强烈的选择压力很可能推动了产生和保存热量的生理过程的增强。然而，尽管人类已经在寒冷气候中生活了几千年，我们仍然对这种适应过程是如何在遗传水平上发生的知之甚少。西伯利亚的土著居民长期居住在地球上最寒冷的气候中，为研究抗寒性的遗传基础提供了最好的机会。在最后一个冰期，北欧大部分地区都被冰覆盖，而西伯利亚相对来说没有冰，考古证据表明，人们在这个地区居住了4万多年。人类在这一地区成功的长期定居无疑需要多种适应，以应对长期的严寒胁迫、剧烈的光周期变化以及有限且高度多变的食物资源。该项目将收集生活在西伯利亚大片地区的15个种群的全基因组多态性数据，从西伯利亚南部地区到北极圈内泰米尔半岛最北端的定居点。这些适应寒冷气候的人群的变异模式将与生活在温暖气候下的中亚和东亚人群的变异模式进行比较。将特别关注包含先前与冷适应有关的基因的基因组区域，或在与能量代谢或冷适应性状相关的已知途径中起作用的基因区域。密集的遗传数据、广泛的地理人口覆盖范围和几种检测自然选择特征的有力方法相结合，将提供迄今为止人类对寒冷的遗传适应的最全面的图景。

Our species originated in Africa, and subsequently dispersed to all other continents except Antarctica. During this dispersal, human populations were exposed to a variety of climates that differed substantially from those in their African homeland. Nowhere do these climatic conditions differ more dramatically than in the far northern reaches of Siberia. Indeed, humans represent the only primate species other than the Japanese macaque that has adapted to boreal conditions?where temperatures remain far below freezing for more than half the year?pointing to intense selection pressures that likely drove the enhancement of physiological processes that generate and conserve heat. However, despite the fact that humans have lived in cold climates for millennia, we still know very little about how this process of adaptation occurred at the genetic level. The native populations of Siberia provide the best opportunity to investigate the genetic basis of cold resistance given their long-term residence in some of the coldest climates on earth. While much of northern Europe was under ice throughout the last glacial period, Siberia remained relatively ice free, and archaeological evidence suggests that people inhabited this region for more than 40,000 years. The successful long-term settlement of this area by humans undoubtedly required multiple adaptations to deal with the extended severe cold stress, dramatic variation in photoperiod, and limited and highly variable food resources. This project will gather genome-wide polymorphism data from 15 populations that live across a large area of Siberia, from regions of southern Siberia to the northernmost settlements on the Taymyr peninsula within the Arctic Circle. Patterns of variation in these cold-adapted populations will be compared with those from Central and East Asian populations that live in warmer climates. Particular attention will be paid to genomic regions containing genes that have been previously implicated in cold adaptation, or that function in known pathways connected to energy metabolism or cold-adapted traits. The combination of dense genetic data, wide geographic population coverage, and several powerful methods for detecting the signatures of natural selection will offer the most comprehensive picture of genetic adaptation to cold in humans to date.