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Mol Biol Evol:中科院昆明动物所张亚平研究组等揭示非洲家犬抵御疟原虫侵害遗传机制

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摘要 : 2017年10月1日,国际分子生物学和进化领域的权威期刊《Molecular Biology and Evolution》杂志在线发表了中国科学院昆明动物研究所张亚平院士团队的一篇研究论文,研究揭示了非洲家犬抵御疟原虫侵害遗传机制。
2017年10月1日,国际分子生物学和进化领域的权威期刊《molecular Biology and Evolution》杂志在线发表了中国科学院昆明动物研究所张亚平院士团队的一篇研究论文,研究揭示了非洲家犬抵御疟原虫侵害遗传机制。 家犬约在3万多年前从东亚的灰狼驯化而来,并于1万多年前迁移到达非洲,现已遍布世界大部分有人类居住的地方。家犬的扩散历史以及对不同自然环境的适应性进化,是进化生物学家研究的热点。非洲较强的紫外线、较高的温度和疟疾肆虐的环境,家犬迁移到非洲的群体历史和如何适应当地自然环境尚未得到系统研究。 研究组对收集到的非洲尼日利亚6个城市的15个家犬样品,以及来自非洲不同国家的4只非洲金豺(Canis anthus)样品进行了全基因组测序。群体遗传结构分析显示,非洲家犬有独立的遗传组分。群体历史模拟显示,家犬约1万4千年前迁移到非洲(图1)。经历一次强烈的瓶颈效应后,非洲家犬与非洲金豺发生基因交流。全基因组选择信号扫描分析显示,非洲家犬群体在抗疟疾、免疫反应、紫外线保护等相关信号通路受到自然选择的作用。研究人员集中对ADGRE1基因开展深入研究,发现该基因与非洲人群对疟疾的易感性相关。通过疟原虫侵染小鼠巨噬细胞系实验,证明ADGRE1基因参与了巨噬细胞对疟原虫的胞吞作用,并通过加强I型干扰素通路相关基因的表达量抵抗疟原虫的侵染(图2)。非洲犬特有的非同义突变(G655A)能够加强ADGRE1基因的功能。 研究首次揭示家犬在伴随人类的过程中适应非洲炎热自然环境的遗传机制,并为今后非洲人群疟疾研究工作提供重要靶点和参考。
图1.非洲家犬的群体历史。

图2.ADGRE1-G655A突变在非洲家犬中增强对疟原虫感染的抵抗。
原文链接: Whole-genome sequencing of African dogs provides insights into adaptations against tropical parasites 原文摘要: Natural selection in domestic dogs is of great interest in evolutionary biology since dogs have migrated to every inhabited continent of the world alongside humans, and adapted to diverse environments. Here, we explored their demographic history and genetic basis of adaptation to the tropical African environment using whole genome analyses of 19 African indigenous dogs from Nigeria. Demographic analysis suggests that the ancestors of these dogs migrated into Africa from Eurasia 14,000 years ago and underwent a severe founder effect before population expansion. Admixture analysis further reveals that African dog genomes contain about 1.88%-3.50% introgression from African golden wolves (Canis anthus). Population genetic analysis identifies 50 positively selected genes linked with immunity, angiogenesis, ultraviolet protection, as well as insulin secretion and sensitivity that may contribute to adaptation to tropical conditions. One of the positively selected genes, ADGRE1 (adhesion G protein-coupled receptor E1), has also been found to be association with severe malaria resistance in African human populations. Functional assessments showed that ADGRE1 provides protective host defense against Plasmodium infections. This result, together with the fact that the inflammatory response to canine babesiosis is similar to complicated falciparum malaria in humans, support the dogs as a model for the study of malaria control and treatment. doi:10.1093/molbev/msx258 作者:张亚平 点击:
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