Pleiotropy promotes the evolution of inducible immune responses in a model of host-pathogen coevolution.
Pleiotropy promotes the evolution of inducible immune responses in a model of host-pathogen coevolution.
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DOI：
10.1371/journal.pcbi.1010445
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发表时间：
2023-04
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
--
作者：
免疫系统的组成部分面临着巨大的选择压力，需要有效地利用生物资源、减轻感染和抵抗寄生操纵。理论上最佳的免疫防御根据遇到的寄生虫种类平衡对组成型和诱导型免疫成分的投资，但遗传和动态约束可能会迫使偏离理论最佳值。其中一个潜在的限制是多效性，即单个基因影响多个表型的现象。尽管多效性可以阻止或显着减缓适应性进化，但它在构成后生动物免疫系统的信号网络中普遍存在。我们假设，尽管适应性进化减慢，但免疫信号网络中仍保持多效性，因为它提供了一些其他优势，例如迫使网络进化以在感染期间增加宿主适应性的方式进行补偿。为了研究多效性对免疫信号网络进化的影响，我们使用基于代理的建模方法来进化被同时共同进化的寄生虫感染的宿主免疫系统群体。四种对进化性的多效性限制被纳入网络中，并将它们的进化结果与非多效性网络进行比较和竞争。随着网络的发展，我们跟踪了免疫网络复杂性的几个指标、诱导防御和本构防御的相对投资，以及与竞争模拟的赢家和输家相关的特征。我们的结果表明，无论寄生虫的流行程度如何，非多效性网络都会进化为部署高度组成型免疫反应，但多效性的一些实现有利于高度诱导免疫的进化。这些诱导多效性网络的拟合度不亚于非多效性网络，并且可以在竞争性模拟中击败非多效性网络。这些为免疫系统中多效性基因的普遍存在提供了理论解释，并强调了一种可以促进诱导性免疫反应进化的机制。参与免疫防御的基因是适应性进化的热点，因为它们能抵抗快速进化的寄生虫和病原体。影响多个离散性状的多效性基因已被证明以比非多效性基因慢得多的速度进化，但在免疫系统中具有高度代表性。人们对多效性信号基因对免疫进化的进化影响知之甚少，因此我们开发了多效性信号网络进化模型来解决这一知识空白。我们的结果表明，多效性可能是诱导免疫发展中的一个重要基因组特征。
Components of immune systems face significant selective pressure to efficiently use organismal resources, mitigate infection, and resist parasitic manipulation. A theoretically optimal immune defense balances investment in constitutive and inducible immune components depending on the kinds of parasites encountered, but genetic and dynamic constraints can force deviation away from theoretical optima. One such potential constraint is pleiotropy, the phenomenon where a single gene affects multiple phenotypes. Although pleiotropy can prevent or dramatically slow adaptive evolution, it is prevalent in the signaling networks that compose metazoan immune systems. We hypothesized that pleiotropy is maintained in immune signaling networks despite slowed adaptive evolution because it provides some other advantage, such as forcing network evolution to compensate in ways that increase host fitness during infection. To study the effects of pleiotropy on the evolution of immune signaling networks, we used an agent-based modeling approach to evolve a population of host immune systems infected by simultaneously co-evolving parasites. Four kinds of pleiotropic restrictions on evolvability were incorporated into the networks, and their evolutionary outcomes were compared to, and competed against, non-pleiotropic networks. As the networks evolved, we tracked several metrics of immune network complexity, relative investment in inducible and constitutive defenses, and features associated with the winners and losers of competitive simulations. Our results suggest non-pleiotropic networks evolve to deploy highly constitutive immune responses regardless of parasite prevalence, but some implementations of pleiotropy favor the evolution of highly inducible immunity. These inducible pleiotropic networks are no less fit than non-pleiotropic networks and can out-compete non-pleiotropic networks in competitive simulations. These provide a theoretical explanation for the prevalence of pleiotropic genes in immune systems and highlight a mechanism that could facilitate the evolution of inducible immune responses. Genes involved in immune defense are hotspots of adaptive evolution as they resist rapidly evolving parasites and pathogens. Pleiotropic genes, which affect multiple discrete traits, have been shown to evolve at a much slower rate than non-pleiotropic genes but are highly represented in the immune system. The evolutionary effects of pleiotropic signaling genes on immune evolution are poorly understood, so we developed a model of pleiotropic signaling network evolution to address this gap in knowledge. Our results show that pleiotropy may be an important genomic feature in the development of inducible immunity.
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影响因子：
32.4
作者：
Luecke S;Sheu KM;Hoffmann A
通讯作者：
Hoffmann A
影响因子：
10.7
作者：
Fraisse, Christelle;Sala, Gemma Puixeu;Vicoso, Beatriz
通讯作者：
Vicoso, Beatriz
DOI：
10.1098/rspb.2018.0658
发表时间：
2018-07-25
期刊：
Proceedings. Biological sciences
影响因子：
--
作者：
Boots M;Best A
通讯作者：
Best A
DOI：
10.1093/plcell/koac076
发表时间：
2022-07-04
期刊：
The Plant cell
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Lenski, RE;Ofria, C;Adami, C
通讯作者：
Adami, C