Mullinax Sarah R, Darby Andrea M, Gupta Anjali, Chan Patrick, Smith Brittny R, Unckless Robert L
Department of Molecular Biosciences, University of Kansas, Lawrence, United States.
Department of Entomology, Cornell University, Ithaca, United States.
Elife. 2025 May 30;12:RP90638. doi: 10.7554/eLife.90638.
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.
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。