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一系列选择压力支持免疫肽等位基因的维持。

A suite of selective pressures supports the maintenance of alleles of a immune peptide.

作者信息

Mullinax Sarah R, Darby Andrea M, Gupta Anjali, Chan Patrick, Smith Brittny R, Unckless Robert L

机构信息

Department of Molecular Biosciences, University of Kansas, Lawrence, United States.

Department of Entomology, Cornell University, Ithaca, United States.

出版信息

Elife. 2025 May 30;12:RP90638. doi: 10.7554/eLife.90638.

DOI:10.7554/eLife.90638
PMID:40445192
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12124834/
Abstract

The innate immune system provides hosts with a crucial first line of defense against pathogens. While immune genes are often among the fastest evolving genes in the genome, in , antimicrobial peptides (AMPs) are notable exceptions. Instead, AMPs may be under balancing selection, such that over evolutionary timescales, multiple alleles are maintained in populations. In this study, we focus on the AMP Diptericin A, which has a segregating amino acid polymorphism associated with differential survival after infection with the Gram-negative bacteria . Diptericin A also helps control opportunistic gut infections by common gut microbes, especially those of . In addition to genotypic effects on gut immunity, we also see strong sex-specific effects that are most prominent in flies without functional . To further characterize differences in microbiomes between different genotypes, we used 16S metagenomics to look at the microbiome composition. We used both lab-reared and wild-caught flies for our sequencing and looked at overall composition as well as the differential abundance of individual bacterial families. Overall, we find flies that are homozygous for one allele of are better equipped to survive a systemic infection from , but in general have a shorter lifespans after being fed common gut commensals. Our results suggest a possible mechanism for the maintenance of genetic variation of through the complex interactions of sex, systemic immunity, and the maintenance of the gut microbiome.

摘要

先天免疫系统为宿主提供了抵御病原体的关键第一道防线。虽然免疫基因通常是基因组中进化最快的基因之一,但抗菌肽(AMPs)却是显著的例外。相反,抗菌肽可能处于平衡选择之下,以至于在进化时间尺度上,群体中维持着多个等位基因。在本研究中,我们聚焦于抗菌肽双翅菌素A,它具有一个与感染革兰氏阴性菌后不同存活率相关的分离氨基酸多态性。双翅菌素A还有助于控制常见肠道微生物,尤其是那些[未提及具体细菌名称]引起的机会性肠道感染。除了对肠道免疫的基因型效应外,我们还观察到强烈的性别特异性效应,这在没有功能性[未提及具体功能]的果蝇中最为突出。为了进一步表征不同基因型之间微生物群的差异,我们使用16S宏基因组学来研究微生物群组成。我们使用实验室饲养和野外捕获的果蝇进行测序,并观察总体组成以及各个细菌家族的差异丰度。总体而言,我们发现对于[未提及具体基因名称]的一个等位基因纯合的果蝇更有能力在[未提及具体细菌名称]引起的全身感染中存活,但一般在喂食常见肠道共生菌后寿命较短。我们的结果表明,通过性别、全身免疫和肠道微生物群维持之间的复杂相互作用,可能存在一种维持[未提及具体基因名称]遗传变异的机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/9387acf6a693/elife-90638-fig5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/c8e1e202c3ce/elife-90638-fig3-figsupp2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/a63b0591f305/elife-90638-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/9387acf6a693/elife-90638-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/9e3555113980/elife-90638-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/a7edccc54cac/elife-90638-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/b7ffa0d4f0ce/elife-90638-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/59210466731d/elife-90638-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/60488f81e9e0/elife-90638-fig2-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/e0008808d57d/elife-90638-fig2-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/da468ed6b958/elife-90638-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/0e40947031e5/elife-90638-fig3-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/c8e1e202c3ce/elife-90638-fig3-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/693e465c1888/elife-90638-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/0937d9dd8a24/elife-90638-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/68c5b3e65f61/elife-90638-fig4-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/a63b0591f305/elife-90638-fig4-figsupp3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4529/12124834/9387acf6a693/elife-90638-fig5.jpg

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本文引用的文献

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PLoS Genet. 2024 Mar 11;20(3):e1011155. doi: 10.1371/journal.pgen.1011155. eCollection 2024 Mar.
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The genetic basis of variation in immune defense against Lysinibacillus fusiformis infection in Drosophila melanogaster.果蝇对梭菌感染免疫防御的遗传基础。
PLoS Pathog. 2023 Aug 7;19(8):e1010934. doi: 10.1371/journal.ppat.1010934. eCollection 2023 Aug.
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Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in .
生态相关细菌驱动宿主抗菌肽的进化。
Science. 2023 Jul 21;381(6655):eadg5725. doi: 10.1126/science.adg5725.
4
Intestinal Immune Deficiency and Juvenile Hormone Signaling Mediate a Metabolic Trade-off in Adult Females.肠道免疫缺陷与保幼激素信号传导介导成年雌性的代谢权衡。
Metabolites. 2023 Feb 24;13(3):340. doi: 10.3390/metabo13030340.
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Antimicrobial peptides do not directly contribute to aging in Drosophila, but improve lifespan by preventing dysbiosis.抗菌肽并不直接导致果蝇衰老,而是通过防止菌群失调来延长寿命。
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Ageing leads to reduced specificity of antimicrobial peptide responses in .衰老导致抗菌肽反应的特异性降低。
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The Role of Microbiota in Aging.微生物群在衰老中的作用。
Front Aging. 2022 May 19;3:909509. doi: 10.3389/fragi.2022.909509. eCollection 2022.
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The impact of the gut microbiome on extra-intestinal autoimmune diseases.肠道微生物群对肠外自身免疫性疾病的影响。
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