生物复杂性状的形成和演化受到内在（如突变和重组）和外在（如环境压力）力量驱动。新突变在人类短暂的进化历程中不多见，在群体中达到高频的更是罕见。而基因组中既有变异的重新组合（重组）可能对复杂性状的演化有更显著的效应。本项目拟充分利用西北地区东西方基因交流产生的混合人群基因组和性状融合的优势，研究基因交流与重组对人群复杂性状形成和环境适应的影响机制。基于前期建立的方法，整合基因组、转录组和可观察度量的表型数据，研究重组基因组与性状的内在联系和动力学机制。研究中把复杂性状分为一般性状（如体质特征和基因表达谱）和适应性性状（仅作为特例）；着重考虑既有遗传变异在混合人群中的重新组合效应——多基因相互作用；主要研究遗传混合与重组对一般性状形成和演化的驱动机制，保证本项目对微观进化基本理论和一般规律探讨的可行性；其次研究遗传混合与重组对适应性性状的内在驱动，为进一步探讨基因-环境相互作用机制奠定基础。

The evolution of complex traits is driven by both intrinsic (e.g. mutation and recombination) and extrinsic (environmental pressure) forces. Novel mutations are not common in human genome due to the short history of human populations, and those that can reach high frequency are even rare. However, recombination, the process by which genome is broken and joined in other genetic material, could contribute considerably and significantly to human complex traits evolution. Especially, in human, the recombination of existing genetic variations could have substantial effect on the appearance and evolution of complex traits. In this project, taking advantage of the recombined genomes and highly diverse phenotypes in admixed populations in northwestern China, which were formed by large-scale gene flow between western and eastern Eurasian populations, we plan to systematically explore the general principles and mechanisms of genetic admixture and recombination driving the evolution of complex traits in human. By integrating genomic, transcriptomic, and the measurable phenotypic and environmental data, we base mainly on the methods and platforms established previously for admixture analysis, and focus on genetic admixture and recombination as intrinsic driving forces of the evolution of human complex traits. In this proposed project, we plan to primarily study general phenotypes in human populations such as physical anthropological traits and gene expression profiles, and we attempt to dissect the potential contribution of genetic admixture and recombination. In addition, we are also interested in those traits that are associated with local adaptation of human populations, but this part will not be the main aim of this project. We concentrate on the general principle of microevolution and try to firstly reveal the driving mechanism of genetic admixture and recombination on general phenotypes of human populations which, however, are not necessarily adaptive. We expect the study on adaptive traits, if existing, to provide some basis for further study on gene-environment interaction in the evolution of human complex traits/diseases.

本项目旨在研究我国人群的遗传混合及其在人类复杂性状尤其是适应性性演化过程中的作用和机制。本项目的实施，完成了以下方面的的工作并取得了相应的进展和结果：（1）对混合人群的祖先来源染色体片段分布进行理论推导；进一步对人类基因组中的重组事件进行估计和数学建模；（2）发展了一系列研究人群遗传混合历史和混合模型的方法（MALDmef，CAMer，AdmixInfer v1.0.4，AdmixSim v1.0.2， MultiWaver）等5个方法，检测人群特异性拷贝数变异的工具WinXPCNVer，以及检测遗传渗入ArchaicSeeker；（3）分析了维吾尔族和青藏高原人群的全基因组数据，并研究了这些族群的遗传起源、基因交流历史等；（4）研究了遗传混合对青藏高原人群适应高原低氧环境的进化遗传学机制；（5）发展的方法对应的计算机软件均已经公开发表在同行评议期刊，并发布了相应软件源代码和计算机应用程序（http://www.picb.ac.cn/PGG/resource.php）；（6）项目执行期间，共发表论文39篇（均已标注本项目基金号：91331204），其中30篇论文以项目负责人为通讯作者。其中5篇通讯作者论文（第一署名单位）发表在SCI收录的5-year影响因子大于10的学术期刊，分别发表在基因组生物学Genome Biology（1篇），核酸研究NAR （1篇），美国人类遗传学杂志Am.J.Hum.Genet.（2篇），和分子生物学与进化Mol.Biol.Evol.（1篇）。一篇论文（Am.J.Hum.Genet.通讯作者）被Scientific American专文报道；另一篇论文（J Med Genet，通讯作者）被期刊编辑选为“亮点论文”。本项目的研究成果增强了我们对我国以及亚洲人群的基因交流历史的了解，加深了我们对遗传混合/遗传渗入影响人类适应环境的机制的认识，特别地，促进了从遗传混合角度对青藏高原人群适应高原环境的遗传和微观进化机制的研究。