Rapid Evolution of Glycan Recognition Receptors Reveals an Axis of Host-Microbe Arms Races beyond Canonical Protein-Protein Interfaces.
Rapid Evolution of Glycan Recognition Receptors Reveals an Axis of Host-Microbe Arms Races beyond Canonical Protein-Protein Interfaces.
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DOI：
10.1093/gbe/evad119
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发表时间：
2023-07-03
影响因子：
3.3
通讯作者：
Elde, Nels C.
中科院分区：
文献类型：
--
作者：
Hilbert, Zoe A.;Haffener, Paige E.;Young, Hannah J.;Schwiesow, Mara J. W.;Leffler, Ellen M.;Elde, Nels C.
关键词：
检测微生物病原体是许多哺乳动物免疫蛋白的主要功能。这是通过识别多种微生物产生的大分子（包括蛋白质、核酸和碳水化合物）来实现的。病原体通过快速改变这些结构以避免被发现来破坏宿主的防御，从而对反复适应以保持有效的宿主免疫蛋白施加强大的选择压力。在涉及致病蛋白底物检测的许多免疫蛋白中已经鉴定出快速进化的特征，但是在与其他类型的病原体衍生分子相互作用的宿主蛋白中是否可以观察到类似的信号却受到较少的关注。这种对蛋白质-蛋白质界面的关注在很大程度上掩盖了对真菌作为宿主-病原体冲突的贡献者的研究，尽管它们作为一类强大的脊椎动物病原体很重要。在这里，我们提供的证据表明，参与微生物聚糖检测的哺乳动物免疫受体一直受到反复的正选择。我们发现这些基因中快速进化的位点聚集在涉及碳水化合物识别的关键功能域中。此外，我们还确定了一种特定基因 MelLec 的取代趋同模式和平衡选择的证据，该基因在控制侵袭性真菌病方面发挥着关键作用。我们的结果还强调了进化分析的力量，通过识别像 CLEC12A 这样的基因，在哺乳动物谱系中具有强烈的正选择信号，从而揭示宿主与病原体冲突的未表征的界面。这些结果表明，宿主-微生物冲突形成的界面领域超出了宿主-病毒蛋白质-蛋白质相互作用的世界，进入了微生物聚糖和真菌的世界。
Detection of microbial pathogens is a primary function of many mammalian immune proteins. This is accomplished through the recognition of diverse microbial-produced macromolecules including proteins, nucleic acids, and carbohydrates. Pathogens subvert host defenses by rapidly changing these structures to avoid detection, placing strong selective pressures on host immune proteins that repeatedly adapt to remain effective. Signatures of rapid evolution have been identified in numerous immunity proteins involved in the detection of pathogenic protein substrates, but whether similar signals can be observed in host proteins engaged in interactions with other types of pathogen-derived molecules has received less attention. This focus on protein–protein interfaces has largely obscured the study of fungi as contributors to host–pathogen conflicts, despite their importance as a formidable class of vertebrate pathogens. Here, we provide evidence that mammalian immune receptors involved in the detection of microbial glycans have been subject to recurrent positive selection. We find that rapidly evolving sites in these genes cluster in key functional domains involved in carbohydrate recognition. Further, we identify convergent patterns of substitution and evidence for balancing selection in one particular gene, MelLec, which plays a critical role in controlling invasive fungal disease. Our results also highlight the power of evolutionary analyses to reveal uncharacterized interfaces of host–pathogen conflict by identifying genes, like CLEC12A, with strong signals of positive selection across mammalian lineages. These results suggest that the realm of interfaces shaped by host–microbe conflicts extends beyond the world of host–viral protein–protein interactions and into the world of microbial glycans and fungi.
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影响因子：
3.6
作者：
de Jong MA;Vriend LE;Theelen B;Taylor ME;Fluitsma D;Boekhout T;Geijtenbeek TB
通讯作者：
Geijtenbeek TB
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
7
作者：
George, Renee D.;McVicker, Graham;Thomas, James H.
通讯作者：
Thomas, James H.
影响因子：
64.8
作者：
Elde NC;Child SJ;Geballe AP;Malik HS
通讯作者：
Malik HS
影响因子：
8.8
作者：
Begun J;Lassen KG;Jijon HB;Baxt LA;Goel G;Heath RJ;Ng A;Tam JM;Kuo SY;Villablanca EJ;Fagbami L;Oosting M;Kumar V;Schenone M;Carr SA;Joosten LA;Vyas JM;Daly MJ;Netea MG;Brown GD;Wijmenga C;Xavier RJ
通讯作者：
Xavier RJ