An Evolution-Based Screen for Genetic Differentiation between Anopheles Sister Taxa Enriches for Detection of Functional Immune Factors.
An Evolution-Based Screen for Genetic Differentiation between Anopheles Sister Taxa Enriches for Detection of Functional Immune Factors.
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DOI：
10.1371/journal.ppat.1005306
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发表时间：
2015-12
期刊：
影响因子：
6.7
通讯作者：
Vernick KD
中科院分区：
文献类型：
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作者：
Mitri C;Bischoff E;Takashima E;Williams M;Eiglmeier K;Pain A;Guelbeogo WM;Gneme A;Brito-Fravallo E;Holm I;Lavazec C;Sagnon N;Baxter RH;Riehle MM;Vernick KD
物种间的核苷酸变异模式是由自然选择过程形成的，包括暴露于环境病原体。我们研究了两个姐妹物种的遗传变异模式，冈比亚按蚊和按蚊coluzzii，这两个有效的自然载体的人疟疾在西非。我们使用了由A. coluzzii设计了一个群体遗传筛选器，对一组26个潜在的免疫基因进行了分类，以与签名一致，并对它们的免疫表型进行了功能测试。筛选结果对具有保护性免疫表型的基因具有强预测性：符合筛选标准的基因比不符合标准的基因更有可能显示出抗疟疾感染的功能表型（p = 0.0005）。因此，基于进化的筛选可以有效地优先考虑用于劳动密集型下游功能测试的候选基因，并且安全地允许排除不满足筛选标准的基因。具有类似于APL 1-TEP 1选择性扫描特征的免疫基因组似乎在A. coluzzii基因组比以前认识的。免疫基因的分化可能是A. coluzzii在从A.冈比亚，虽然作用，如果任何自然选择的疟原虫是未知的。筛选的应用允许鉴定新的功能性免疫因子，并将新的功能分配给已知因子。我们描述了免疫蛋白之间的生物化学结合相互作用，疟疾感染的功能活动的基础，这突出了病原体特异性和免疫复合物的结构之间的相互作用。我们还发现，大多数疟疾保护性免疫因子显示人类或啮齿动物疟疾的表型，具有广泛的特异性是罕见的。 冈比亚按蚊和科氏按蚊是西非人类疟疾的主要蚊媒。这两个密切相关的物种都有效地传播疾病，尽管它们表现出生态差异。前期工作表明，A. coluzzii在蚊子免疫的重要基因中显示出独特的遗传模式。在这里，我们使用这种遗传模式作为过滤器来检查一组潜在的免疫基因，并表明遗传模式对疟疾寄生虫测试时在免疫中发挥功能作用的基因具有强烈的预测性。
Nucleotide variation patterns across species are shaped by the processes of natural selection, including exposure to environmental pathogens. We examined patterns of genetic variation in two sister species, Anopheles gambiae and Anopheles coluzzii, both efficient natural vectors of human malaria in West Africa. We used the differentiation signature displayed by a known coordinate selective sweep of immune genes APL1 and TEP1 in A. coluzzii to design a population genetic screen trained on the sweep, classified a panel of 26 potential immune genes for concordance with the signature, and functionally tested their immune phenotypes. The screen results were strongly predictive for genes with protective immune phenotypes: genes meeting the screen criteria were significantly more likely to display a functional phenotype against malaria infection than genes not meeting the criteria (p = 0.0005). Thus, an evolution-based screen can efficiently prioritize candidate genes for labor-intensive downstream functional testing, and safely allow the elimination of genes not meeting the screen criteria. The suite of immune genes with characteristics similar to the APL1-TEP1 selective sweep appears to be more widespread in the A. coluzzii genome than previously recognized. The immune gene differentiation may be a consequence of adaptation of A. coluzzii to new pathogens encountered in its niche expansion during the separation from A. gambiae, although the role, if any of natural selection by Plasmodium is unknown. Application of the screen allowed identification of new functional immune factors, and assignment of new functions to known factors. We describe biochemical binding interactions between immune proteins that underlie functional activity for malaria infection, which highlights the interplay between pathogen specificity and the structure of immune complexes. We also find that most malaria-protective immune factors display phenotypes for either human or rodent malaria, with broad specificity a rarity. Anopheles gambiae and Anopheles coluzzii are the primary mosquito vectors of human malaria in West Africa. Both of these closely related species efficiently transmit the disease, although they display ecological differences. Previous work showed that A. coluzzii displays distinct genetic patterns in genes important for mosquito immunity. Here, we use this genetic pattern as a filter to examine a panel of potential immune genes, and show that the genetic pattern is strongly predictive for genes that play a functional role in immunity when tested with malaria parasites.