A worldwide analysis of beta-defensin copy number variation suggests recent selection of a high-expressing DEFB103 gene copy in East Asia.
A worldwide analysis of beta-defensin copy number variation suggests recent selection of a high-expressing DEFB103 gene copy in East Asia.
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DOI：
10.1002/humu.21491
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发表时间：
2011-07
期刊：
影响因子：
3.9
通讯作者：
Hollox, Edward J.
中科院分区：
文献类型：
--
作者：
Hardwick, Robert J.;Machado, Lee R.;Zuccherato, Luciana W.;Antolinos, Suzanne;Xue, Yali;Shawa, Nyambura;Gilman, Robert H.;Cabrera, Lilia;Berg, Douglas E.;Tyler-Smith, Chris;Kelly, Paul;Tarazona-Santos, Eduardo;Hollox, Edward J.
β-防御素是一个多功能基因家族，在防御病原体、生殖和色素沉着中发挥作用。在人类中，六个β-防御素基因聚集在一个重复区域中，该区域以拷贝数可变（CNV）为块，二倍体拷贝数在1到12之间。在宿主防御中的作用使得这种CNV的进化史特别有趣，因为传染病引起的发病率可能是人类进化中的一个重要选择力，并且在地理位置之间存在差异。在这里，我们展示了黑猩猩β-防御素区域的CNV，并确定了人类谱系中含有快速进化的非编码调控序列的β-防御素块。我们还表明，在这些快速发展的序列之一的变化影响表达水平和细胞因子的反应DEFB 103，流感病毒融合在细胞表面的关键抑制剂。在67个人群中对β-防御素CNV进行的全球分析显示，在东亚（历史和现代流感流行的地理起源），高DEFB 103表达拷贝的频率异常高，这可能是该地区对流感抗性增加的选择的结果。Mutat 32：743-750，2011.© 2011 Wiley-Liss公司。
Beta-defensins are a family of multifunctional genes with roles in defense against pathogens, reproduction, and pigmentation. In humans, six beta-defensin genes are clustered in a repeated region which is copy-number variable (CNV) as a block, with a diploid copy number between 1 and 12. The role in host defense makes the evolutionary history of this CNV particularly interesting, because morbidity due to infectious disease is likely to have been an important selective force in human evolution, and to have varied between geographical locations. Here, we show CNV of the beta-defensin region in chimpanzees, and identify a beta-defensin block in the human lineage that contains rapidly evolving noncoding regulatory sequences. We also show that variation at one of these rapidly evolving sequences affects expression levels and cytokine responsiveness of DEFB103, a key inhibitor of influenza virus fusion at the cell surface. A worldwide analysis of beta-defensin CNV in 67 populations shows an unusually high frequency of high-DEFB103-expressing copies in East Asia, the geographical origin of historical and modern influenza epidemics, possibly as a result of selection for increased resistance to influenza in this region. Hum Mutat 32:743–750, 2011. © 2011 Wiley-Liss, Inc.
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