Pathogen-driven selection in the human genome.
Pathogen-driven selection in the human genome.
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DOI：
10.1155/2013/204240
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Sironi M
中科院分区：
文献类型：
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作者：
Cagliani R;Sironi M
传染病和流行病一直伴随着人类历史并成为其特征，是死亡的主要原因之一。即使在今天，尽管卫生和医学研究取得了进展，但据估计，感染仍占死亡人数的15%左右。关于传染病是一种强大的选择压力的假设很早以前就已经形成，但直到大规模遗传数据的可用性和研究分子进化的新方法的发展，我们才能够评估传染性病原体是如何普遍影响人类遗传多样性的。事实上，最近的证据表明，在我们物种进化过程中作为选择压力的各种环境因素中，病原体负荷的影响最大。除了教科书上的主要组织相容性复合体的例子，病原体施加的压力留下的选择签名可以在几个人类基因座上识别，包括不直接参与免疫反应的基因。未来，高通量技术和来自不同人群的遗传数据的可用性可能会为人类宿主及其病原体之间的进化关系提供新的见解。希望这将有助于确定调节传染病易感性的遗传决定因素，并将转化为新的治疗策略。
Infectious diseases and epidemics have always accompanied and characterized human history, representing one of the main causes of death. Even today, despite progress in sanitation and medical research, infections are estimated to account for about 15% of deaths. The hypothesis whereby infectious diseases have been acting as a powerful selective pressure was formulated long ago, but it was not until the availability of large-scale genetic data and the development of novel methods to study molecular evolution that we could assess how pervasively infectious agents have shaped human genetic diversity. Indeed, recent evidences indicated that among the diverse environmental factors that acted as selective pressures during the evolution of our species, pathogen load had the strongest influence. Beside the textbook example of the major histocompatibility complex, selection signatures left by pathogen-exerted pressure can be identified at several human loci, including genes not directly involved in immune response. In the future, high-throughput technologies and the availability of genetic data from different populations are likely to provide novel insights into the evolutionary relationships between the human host and its pathogens. Hopefully, this will help identify the genetic determinants modulating the susceptibility to infectious diseases and will translate into new treatment strategies.