Ancient and recent selective pressures shaped genetic diversity at AIM2-like nucleic acid sensors.
Ancient and recent selective pressures shaped genetic diversity at AIM2-like nucleic acid sensors.
复制标题
古代和最近的选择性压力在AIM2样核酸传感器上塑造了遗传多样性。
DOI：
10.1093/gbe/evu066
复制
发表时间：
2014-04
影响因子：
3.3
通讯作者：
Sironi M
中科院分区：
文献类型：
--
作者：
Cagliani R;Forni D;Biasin M;Comabella M;Guerini FR;Riva S;Pozzoli U;Agliardi C;Caputo D;Malhotra S;Montalban X;Bresolin N;Clerici M;Sironi M
AIM 2样受体（ALR）是针对病毒和细菌的先天免疫应答所必需的核酸传感器家族。我们进行了ALR基因（MNDA，PYHIN 1，IFI 16和AIM 2）的进化分析，通过分析种间和种内的多样性。最大似然分析表明，IFI 16和AIM 2进化自适应灵长类动物，分支特异性选择卡他鼻谱系IFI 16。应用群体遗传学-非遗传学方法也可以鉴定人类谱系中的阳性选择事件。灵长类动物中的阳性选择靶向位于IFI 16和AIM 2中DNA结合界面的位点。在IFI 16中，在灵长类动物和人类谱系中积极选择的几个位点位于PYD结构域中，PYD结构域参与蛋白质-蛋白质相互作用并被人巨细胞病毒免疫逃避蛋白结合。最后，发现正选择靶向IFI 16中的核定位信号和分隔两个HIN结构域的间隔区。人类群体遗传学分析表明，IFI 16基因区一直是长期平衡选择的目标，可能作用于位于间隔区的两个非同义多态性。本文的数据表明，ALR已被自然选择反复靶向。IFI 16中的平衡选择区携带对不同自身免疫性疾病具有相反风险效应的变体，表明拮抗多效性。我们认为，潜在的情况是一个祖先的结果，仍在进行的主机病原体军备竞赛，并在IFI 16的自身免疫性疾病的易感性等位基因的维护代表了一个进化的权衡。
AIM2-like receptors (ALRs) are a family of nucleic acid sensors essential for innate immune responses against viruses and bacteria. We performed an evolutionary analysis of ALR genes (MNDA, PYHIN1, IFI16, and AIM2) by analyzing inter- and intraspecies diversity. Maximum-likelihood analyses indicated that IFI16 and AIM2 evolved adaptively in primates, with branch-specific selection at the catarrhini lineage for IFI16. Application of a population genetics–phylogenetics approach also allowed identification of positive selection events in the human lineage. Positive selection in primates targeted sites located at the DNA-binding interface in both IFI16 and AIM2. In IFI16, several sites positively selected in primates and in the human lineage were located in the PYD domain, which is involved in protein–protein interaction and is bound by a human cytomegalovirus immune evasion protein. Finally, positive selection was found to target nuclear localization signals in IFI16 and the spacer region separating the two HIN domains. Population genetic analysis in humans revealed that an IFI16 genic region has been a target of long-standing balancing selection, possibly acting on two nonsynonymous polymorphisms located in the spacer region. Data herein indicate that ALRs have been repeatedly targeted by natural selection. The balancing selection region in IFI16 carries a variant with opposite risk effect for distinct autoimmune diseases, suggesting antagonistic pleiotropy. We propose that the underlying scenario is the result of an ancestral and still ongoing host–pathogen arms race and that the maintenance of susceptibility alleles for autoimmune diseases at IFI16 represents an evolutionary trade-off.
登录
查看更多内容
影响因子：
4.5
作者：
Gutenkunst RN;Hernandez RD;Williamson SH;Bustamante CD
通讯作者：
Bustamante CD
影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
影响因子：
56.9
作者：
Gabriel, SB;Schaffner, SF;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
10.7
作者：
Fumagalli, Matteo;Cagliani, Rachele;Sironi, Manuela
通讯作者：
Sironi, Manuela
影响因子：
10.7
作者：
Anisimova, M;Bielawski, JP;Yang, ZH
通讯作者：
Yang, ZH