【摘要】 人类(Homo sapiens)起源、迁徙和进化对现代人类遗传多样性具有重要的塑造作用,一直是多学科研究热点.分子遗传学通过现有人群的遗传数据和表型特征来推导、演绎历史事件,提出了"走出非洲完全替换"人类起源模型.在走出非洲迁居世界各地的过程中,不同环境对人类表型和遗传多样性具有重要的选择作用,如人群肤色、身高等外形特征以及乳糖耐受、淀粉代谢、免疫应答和低氧适应等生理特征的表型和遗传多态性演化过程.近年来兴起的人类古DNA研究,通过采集对应事件前、中、后不同时期的古DNA样本,进行全基因组测序,同时系统比较古DNA和现今人群遗传多态性,补充和完善了经典分子遗传学研究结果,可以更全面地分析人类演化历史.基于古基因组研究,学者提出了人类起源的"走出非洲基因渗透"模型,并对上述重要人类表型和遗传多态性的演化史提出了新的证据和观点.本文将对现有人类环境适应的古DNA研究进展进行综述,并据此对自然选择如何塑造人类遗传和表型多态性展开新的讨论,为今后同类研究提供线索.更多还原

【Abstract】 The origin, peopling and evolution of human beings have all contributed greatly to shaping the genetic diversity of present human populations, and are the research focus of multiple disciplines. Molecular genetics has tried to deduce the human history through genetic analysis of modern human populations. It proposed the well-recognized out of Africa human origin model with Homo sapiens replaced all the other human species. As modern humans migrated out of Africa, they encountered multiple environmental conditions which could exert selection pressure upon them, as exemplified by the evolutionary elucidation of human phenotypes like skin pigmentation and height as well as physiological traits like lactase tolerance, starch digestion, immune response and hypoxia adaptation. However, this indirect approach could be largely influenced by undetected population structure and model parameter settings, still cannot fully reveal the genuine human history, and sometimes could even produce misleading results based on Occam’s razor theory. Recently, whole genome resequencing is used to directly analyse ancient DNA samples collected from different time periods to investigate a specific history event. In addition, the genetic data from both ancient and modern human populations are systematically compared to obtain a more straightforward elucidation of human history. To be more specific, analyses from archaic human populations have demonstrated strong evidence of gene flow between Homo sapiens and other extinct human species, e.g. Neanderthals and the Danisova hominin, which gave rise to a leaky replacement model. That is, other ancient human species also have contributed to modern human populations. Together with the remaining Homo sapiens genome, the introgression from ancient human species went through genetic drift and natural selection. For example, the EPAS1 gene encoding endothelial Per-Arnt-Sim(PAS) domain protein 1 has been indicated to play an important role in hypoxia adaptation among Tibetan individuals. 31 SNPs of this gene are significantly associated with haemoglobin(Hb) levels, and the Tibetan dominant alleles are significantly associated with low Hb levels, a trait featured in Tibetan hypoxia adaptation. Interestingly, the dominant Tibetan haplotype can only be observed in Tibetans and Danisova hominin with high frequency, and further genetic analysis revealed this gene was from Danisova hominin. Similar stories could also be observed for other human phenotypes and physiological traits. Therefore, as demonstrated by the illustrious example of EPAS1 gene, ancient DNA research is revealing a human history far more complex than what we have inferred from parsimonious models based on modern DNA. In this review, we will briefly overview some key events in human environmental adaptation in the light of ancient DNA findings, and discuss new evidence how natural selection has shaped human populations, which might provide clues for future studies.更多还原