Receptor adenylate cyclases (RACs) on the surface of trypanosomatids are important players in the host–parasite interface. They detect still unidentified environmental signals that affect the parasites’ responses to host immune challenge, coordination of social motility, and regulation of cell division. A lesser known class of oxygen-sensing adenylate cyclases (OACs) related to RACs has been lost in trypanosomes and expanded mostly in Leishmania species and related insect-dwelling trypanosomatids. In this work, we have undertaken a large-scale phylogenetic analysis of both classes of adenylate cyclases (ACs) in trypanosomatids and the free-living Bodo saltans. We observe that the expanded RAC repertoire in trypanosomatids with a two-host life cycle is not only associated with an extracellular lifestyle within the vertebrate host, but also with a complex path through the insect vector involving several life cycle stages. In Trypanosoma brucei, RACs are split into two major clades, which significantly differ in their expression profiles in the mammalian host and the insect vector. RACs of the closely related Trypanosoma congolense are intermingled within these two clades, supporting early RAC diversification. Subspecies of T. brucei that have lost the capacity to infect insects exhibit high numbers of pseudogenized RACs, suggesting many of these proteins have become redundant upon the acquisition of a single-host life cycle. OACs appear to be an innovation occurring after the expansion of RACs in trypanosomatids. Endosymbiont-harboring trypanosomatids exhibit a diversification of OACs, whereas these proteins are pseudogenized in Leishmania subgenus Viannia. This analysis sheds light on how ACs have evolved to allow diverse trypanosomatids to occupy multifarious niches and assume various lifestyles.

中文翻译：

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锥虫腺苷酸环化酶的大规模系统发育分析揭示了与细胞外生活方式和宿主-病原体相互作用的关联

锥虫表面的受体腺苷酸环化酶 (RAC) 是宿主-寄生虫界面中的重要参与者。他们检测到仍然未知的环境信号，这些信号会影响寄生虫对宿主免疫挑战的反应、社会运动的协调和细胞分裂的调节。与 RAC 相关的一类鲜为人知的氧感应腺苷酸环化酶 (OAC) 已在锥虫中丢失，并且主要在利什曼原虫和相关的昆虫栖息锥虫中扩增。在这项工作中，我们对锥虫和自由生活的Bodo saltans 中的两类腺苷酸环化酶 (AC) 进行了大规模系统发育分析。. 我们观察到具有两个宿主生命周期的锥虫中扩展的 RAC 库不仅与脊椎动物宿主内的细胞外生活方式有关，而且还与通过昆虫载体的复杂路径有关，该路径涉及多个生命周期阶段。在布氏锥虫中，RAC 分为两个主要进化枝，它们在哺乳动物宿主和昆虫载体中的表达谱显着不同。密切相关的刚果锥虫的RAC混合在这两个进化枝中，支持早期的 RAC 多样化。T. brucei亚种失去感染昆虫能力的 RAC 表现出大量的假基因化 RAC，这表明这些蛋白质中的许多在获得单宿主生命周期后变得多余。OAC 似乎是在锥虫中 RAC 扩展之后发生的一项创新。携带内共生体的锥虫表现出 OAC 的多样化，而这些蛋白质在利什曼原虫亚属Viannia 中被假基因化。该分析揭示了 AC 如何进化以允许不同的锥虫占据多种多样的生态位并采取各种生活方式。