Adaptation to Host-Specific Bacterial Pathogens Drives Rapid Evolution of a Human Innate Immune Receptor
Adaptation to Host-Specific Bacterial Pathogens Drives Rapid Evolution of a Human Innate Immune Receptor
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DOI：
10.1016/j.cub.2019.01.058
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发表时间：
2019-02-18
期刊：
影响因子：
9.2
通讯作者：
Hauck, Christof R.
中科院分区：
文献类型：
--
作者：
Adrian, Jonas;Bonsignore, Patrizia;Hauck, Christof R.
感染因子的选择压力是人类和其他哺乳动物进化的主要驱动力。癌胚抗原相关细胞粘附分子（CEACAM）家族的成员充当嗜血杆菌属、螺杆菌属、奈瑟氏菌属和莫拉氏菌属的细菌病原体的受体，其通过不同的表面粘附素与CEACAM接合。虽然微生物附着于上皮CEACAMs促进宿主定植，但CEACAM3（粒细胞表达的吞噬受体）的识别消除了CEACAMs结合细菌。灵长类动物CEACAM3直系同源物的序列分析表明，这种先天免疫受体是进化最快的人类蛋白质之一。特别是，CEACAM3的病原体结合胞外域显示出高度的非同义与同义核苷酸交换，表明异常强的正选择。使用来自不同灵长类动物的CEACAM3结构域，我们发现CEACAM3中发现的氨基酸改变转化为细菌粘附素的特征结合模式。一个这样的氨基酸残基是人和黑猩猩CEACAM3中的F62，其不存在于其他灵长类动物中，并且其对于结合埃及嗜血杆菌的OMP P1粘附素至关重要。将含有F62的基序整合到大猩猩CEACAM3中会导致H吞噬作用的功能获得表型。埃及人。此外，在人类亚群中发现的CEACAM3多态性拓宽了公认的细菌粘附素的谱，表明作用于这种先天免疫受体的正在进行的多变量选择。不同细菌粘附素的物种特异性检测有助于解释CEACAM3在灵长类谱系中异常快速的进化，并提供了人类基因组中红皇后动态的例子。
The selective pressure by infectious agents is a major driving force in the evolution of humans and other mammals. Members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family serve as receptors for bacterial pathogens of the genera Haemophilus, Helicobacter, Neisseria, and Moraxella, which engage CEACAMs via distinct surface adhesins. While microbial attachment to epithelial CEACAMs facilitates host colonization, recognition by CEACAM3, a phagocytic receptor expressed by granulocytes, eliminates CEACAM-binding bacteria. Sequence analysis of primate CEACAM3 orthologs reveals that this innate immune receptor is one of the most rapidly evolving human proteins. In particular, the pathogen-binding extracellular domain of CEACAM3 shows a high degree of non-synonymous versus synonymous nucleotide exchanges, indicating an exceptionally strong positive selection. Using CEACAM3 domains derived from different primates, we find that the amino acid alterations found in CEACAM3 translate into characteristic binding patterns for bacterial adhesins. One such amino acid residue is F62 in human and chimp CEACAM3, which is not present in other primates and which is critical for binding the OMP P1 adhesin of Haemophilus aegyptius. Incorporation of the F62-containing motif into gorilla CEACAM3 results in a gain-of-function phenotype with regard to phagocytosis of H. aegyptius. Moreover, CEACAM3 polymorphisms found in human subpopulations widen the spectrum of recognized bacterial adhesins, suggesting an ongoing multivariate selection acting on this innate immune receptor. The species-specific detection of diverse bacterial adhesins helps to explain the exceptionally fast evolution of CEACAM3 within the primate lineage and provides an example of Red Queen dynamics in the human genome.