國(guó)際著名學(xué)術(shù)期刊《美國(guó)人類(lèi)遺傳學(xué)雜志》（AJHG）在線發(fā)表了上海生命科學(xué)研究院計(jì)算生物學(xué)所徐書(shū)華課題組的最新研究成果Exploring Population Admixture Dynamics via Empirical and Simulated Genome-Wide Distribution of Ancestral Chromosomal Segments,。該研究首先建立了新的方法研究群體混合歷史以及混合動(dòng)力學(xué)機(jī)制,，然后應(yīng)用該方法對(duì)美國(guó)黑人,、墨西哥人等典型混合人群進(jìn)行了具體研究并獲得了比先前更加可靠的結(jié)果和結(jié)論,。
人群混合指的是人群之間的基因交流，通俗地講即人們熟知的“混血”,。通常人們似乎都認(rèn)為混血只是少數(shù)個(gè)體的行為,，但實(shí)際上在人類(lèi)歷史中是很常見(jiàn)的現(xiàn)象?，F(xiàn)代人類(lèi)在其漫長(zhǎng)的歷史長(zhǎng)河中,，遷徙到不同的大洲和島嶼,，先是經(jīng)歷了相當(dāng)長(zhǎng)時(shí)間的彼此隔離，隨后又彼此接觸、交流,，發(fā)生過(guò)同規(guī)模的群體性“混血”事件,，留下了如今各地廣泛存在的“混血”人群，典型的如大家熟識(shí)的美國(guó)黑人,、拉丁美洲人群,、中東和東南亞人群以及我國(guó)新疆的維吾爾族、哈薩克族等,。實(shí)際上,，徐書(shū)華課題組及其合作者之前的研究結(jié)果甚至揭示出包括漢族、藏族,、日本人和韓國(guó)人等在內(nèi)的大部分亞洲人群也是某種程度上的混合人群。因此,，人群之間的基因交流比通常認(rèn)為的更加普遍,。研究混合人群的遺傳結(jié)構(gòu)、基因交流歷史和混合機(jī)制不僅能夠豐富我們對(duì)人類(lèi)自身歷史的認(rèn)識(shí),，同時(shí)對(duì)人類(lèi)微觀進(jìn)化內(nèi)在驅(qū)動(dòng)力的探討提供新的視角,，而且混合人群本身在人類(lèi)復(fù)雜疾病基因的定位研究中有著特殊的實(shí)際應(yīng)用價(jià)值。
該研究首先提出兩種可以用來(lái)研究群體混合歷史和混合動(dòng)力學(xué)機(jī)制的方法：祖先染色體片段分布法和個(gè)體祖先比例分布法,。通過(guò)對(duì)全基因組的模擬數(shù)據(jù)和實(shí)際數(shù)據(jù)進(jìn)行比較分析,，發(fā)現(xiàn)來(lái)自于不同祖先來(lái)源的染色體片段分布比個(gè)體祖先比例分布有更高的統(tǒng)計(jì)效力，且較少的受到抽樣誤差的影響,，并能追溯更久遠(yuǎn)的人群混合歷史,。對(duì)1890個(gè)美國(guó)黑人的全基因組數(shù)據(jù)進(jìn)行分析后發(fā)現(xiàn)，美國(guó)黑人的祖先染色體片段分布更符合14個(gè)世代持續(xù)接受歐洲白人基因流模型（continuous gene flow model）,。該研究還發(fā)現(xiàn)一些美國(guó)黑人的歐洲白人祖先成分要顯著高于基于隨機(jī)婚配模型的計(jì)算機(jī)模擬樣本,，表明美國(guó)黑人人群存在隱藏的群體亞結(jié)構(gòu)，推測(cè)這種群體亞結(jié)構(gòu)很可能由一些美國(guó)黑人家系在歷史上持續(xù)與歐洲白人通婚所導(dǎo)致,。該研究還發(fā)現(xiàn)墨西哥人的混合歷史更加符合24個(gè)世代的漸混模型（gradual admixture model）,，同時(shí)該研究也對(duì)中東一些人群的混合歷史作了探討?？傊?，該項(xiàng)研究成果不僅提供了研究群體混合歷史和形成機(jī)制的新方法，而且豐富了人們對(duì)混合人群歷史的新認(rèn)識(shí),，同時(shí)對(duì)在混合人群中進(jìn)行復(fù)雜疾病研究的實(shí)驗(yàn)設(shè)計(jì),、數(shù)據(jù)分析及結(jié)果解釋有理論指導(dǎo)意義。
該研究工作主要由徐書(shū)華課題組的助理研究員靳文菲博士完成,，合作單位包括復(fù)旦大學(xué),、國(guó)家人類(lèi)基因組南方研究中心和哈佛大學(xué)。該研究工作得到了國(guó)家自然科學(xué)基金委,、上海市科委,、中國(guó)科學(xué)院,、德國(guó)馬普學(xué)會(huì)、香港王寬誠(chéng)教育基金會(huì)等多項(xiàng)基金的資助,。（生物谷Bioon.com）
doi:10.1016 /j.ajhg.2012.09. 008
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Exploring Population Admixture Dynamics via Empirical and Simulated Genome-Wide Distribution of Ancestral Chromosomal Segments
Wenfei Jin, Sijia Wang, Haifeng Wang, Li Jin, Shuhua Xu
The processes of genetic admixture determine the haplotype structure and linkage disequilibrium patterns of the admixed population, which is important for medical and evolutionary studies. However, most previous studies do not consider the inherent complexity of admixture processes. Here we proposed two approaches to explore population admixture dynamics, and we demonstrated, by analyzing genome-wide empirical and simulated data, that the approach based on the distribution of chromosomal segments of distinct ancestry (CSDAs) was more powerful than that based on the distribution of individual ancestry proportions. Analysis of 1,890 African Americans showed that a continuous gene flow model, in which the African American population continuously received gene flow from European populations over about 14 generations, best explained the admixture dynamics of African Americans among several putative models. Interestingly, we observed that some African Americans had much more European ancestry than the simulated samples, indicating substructures of local ancestries in African Americans that could have been caused by individuals from some particular lineages having repeatedly admixed with people of European ancestry. In contrast, the admixture dynamics of Mexicans could be explained by a gradual admixture model in which the Mexican population continuously received gene flow from both European and Amerindian populations over about 24 generations. Our results also indicated that recent gene flows from Sub-Saharan Africans have contributed to the gene pool of Middle Eastern populations such as Mozabite, Bedouin, and Palestinian. In summary, this study not only provides approaches to explore population admixture dynamics, but also advances our understanding on population history of African Americans, Mexicans, and Middle Eastern populations.
