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转: 上海马普所建立检测混合人群自然选择新方法

本帖最后由 ranhaer 于 2012-1-5 12:18 编辑

转自生物谷:
http://www.bioon.com/biology/postgenomics/514598.shtml


Genome Res:金力等建立检测混合人群自然选择新方法


作者:中科院上海生命科学研究院 来源:中科院上海生命科学研究院 2011-12-27 17:31:18

近日,国际著名学术期刊Genome Research在线刊登了上海生科院计算生物学所金力教授等的最新研究成果“Genome-Wide Detection of Natural Selection in African Americans Pre-and Post-Admixture”。该研究充分利用混合人群的群体基因组结构特征,建立了检测现代人群经历大规模基因交流前后受到环境压力下的自然选择信号的分析方法,研究结果对于认识现代人类与环境因素相互作用、适应生存环境以及基因组进化机制具有重要意义。

生物的进化不是完美的,朝任何一个方向的发展都会付出代价。从某种程度上讲,发生在今天人们身上的各种疾病就是进化过程中人类适应生存环境的一些副产物或者必然产物。研究现代人类的环境适应(或者自然对人类的选择),有助于了解基因对性状的影响,建立遗传变异与表型变异之间的相互关系,阐明复杂性状(疾病)的分子与遗传基础,从而对深入了解疾病发生的生物学机制和制定有效治疗方案和开发药物具有指导意义和应用价值。

自然选择不仅发生在几万或几十万年前现代人类的祖先向地球的每一个角落探索和迁移的过程中,在近期的人群迁移和基因交流过程中也会发生。混合人群一般是由彼此隔离分化的祖先人群在近期大规模基因交流产生。隔离分化几万年的人群,从原世居地迁移到数千里之隔的新地域,在近期彼此接触、交流形成新人群。新建立的人群在遗传结构上显著不同于其祖先人群,并且在新居住地新的环境中经历了上十个世代的适应性演变,成为研究现代人类适应新环境可遇而不可求的天然素材。

该项工作利用全基因组数据对典型的近期混合人群——美国黑人进行了研究,发现其在混合前后受到了明显的自然选择。该研究建立了一种检测自然选择的新方法,不但检测到的信号更为可靠,并能很好的解释美国黑人经历的历史和自然环境的变迁。该研究发现,很多受自然选择的基因与美国黑人的高发疾病相关,推测这些高发性疾病可能和美国黑人的非洲祖先最近经历的巨大环境变化有关。另外,该研究还发现,很多抵抗疟疾的等位基因频率在美国黑人中明显降低,反映了北美和非洲的不同病原体在人类基因组中留下了显著的但不同的烙印。同时也提示人类生存环境中的微生物群落和体内的病原体可能是自然选择发生的重要推动力之一。

该研究工作由计算生物学所博士生靳文菲在导师金力教授和徐书华研究员的共同指导下,与国家人类基因组南方研究中心及哈佛儿科医院的研究人员合作完成。该研究工作得到了国家自然科学基金委、上海市科委、中国科学院、德国马普学会、香港王宽诚教育基金会等多项基金的资助。(生物谷Bioon.com)

Genome-Wide Detection of Natural Selection in African Americans Pre-and Post-Admixture
Wenfei Jin1, Shuhua Xu1, Haifeng Wang2, Yongguo Yu3, Yiping Shen4, Bailin Wu4 and Li Jin4,5

It is particularly meaningful to investigate natural selection in African Americans (AfA) due to the high mortality their African ancestry has experienced in history. In this study, we examined 491,526 autosomal SNPs genotyped in 5,210 individuals and conducted a genome-wide search for selection signals in 1,890 AfA. Several genomic regions showing excess of African or European ancestry, which were thought as the footprints of selection since population admixture, were detected based on a commonly used approach. However, we also developed a new strategy to detect natural selection both pre-and post-admixture by reconstructing an ancestral African population (AAF) from inferred African components of ancestry in AfA and comparing it with indigenous African populations (IAF). Interestingly, many selection-candidate genes identified by the new approach were associated with AfA specific high-risk diseases such as prostate cancer and hypertension, suggesting an important role these disease-related genes might have played in adapting to new environment. CD36 and HBB, whose mutations confer a degree of protection against malaria, were also located in the highly differentiated regions between AAF and IAF. Further analysis showed that the frequencies of alleles protecting against malaria in AAF were lower than that in IAF, which consists with the relaxed selection pressure of malaria in the New World. There is no overlap between the top candidate genes detected by the two approaches, indicating the different environmental pressures AfA experienced pre-and post-population-admixture. We suggest that the new approach is reasonably powerful and can also be applied to other admixed populations such as Latinos and Uyghurs.

发表于:
http://genome.cshlp.org/content/early/2011/11/29/gr.124784.111

徐书华的主页:
http://www.picb.ac.cn/~xushua/index.files/RecentPublications.htm

上海马普所的主页:
http://www.picb.ac.cn/picb-dynamic/index.htm
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