Comprising more than 1,400 species, bats possess adaptations unique among mammals including powered flight, unexpected longevity, and extraordinary immunity. Some of the molecular mechanisms underlying these unique adaptations includes DNA repair, metabolism and immunity. However, analyses have been limited to a few divergent lineages, reducing the scope of inferences on gene family evolution across the Order Chiroptera. We conducted an exhaustive comparative genomic study of 37 bat species, one generated in this study, encompassing a large number of lineages, with a particular emphasis on multi-gene family evolution across immune and metabolic genes. In agreement with previous analyses, we found lineage-specific expansions of the APOBEC3 and MHC-I gene families, and loss of the proinflammatory PYHIN gene family. We inferred more than 1,000 gene losses unique to bats, including genes involved in the regulation of inflammasome pathways such as epithelial defence receptors, the natural killer gene complex and the interferon-gamma induced pathway. Gene set enrichment analyses revealed genes lost in bats are involved in defence response against pathogen-associated molecular patterns and damage-associated molecular patterns. Gene family evolution and selection analyses indicate bats have evolved fundamental functional differences compared to other mammals in both innate and adaptive immune system, with the potential to enhance antiviral immune response while dampening inflammatory signalling. In addition, metabolic genes have experienced repeated expansions related to convergent shifts to plant-based diets. Our analyses support the hypothesis that, in tandem with flight, ancestral bats had evolved a unique set of immune adaptations whose functional implications remain to be explored.

中文翻译：

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大规模基因组采样揭示了蝙蝠独特的免疫和代谢适应

蝙蝠包含 1,400 多种物种，在哺乳动物中具有独特的适应性，包括动力飞行、意想不到的长寿和非凡的免疫力。这些独特适应背后的一些分子机制包括 DNA 修复、新陈代谢和免疫。然而，分析仅限于几个不同的谱系，从而减少了对跨翼手目基因家族进化的推断范围。我们对本研究中产生的 37 种蝙蝠物种进行了详尽的比较基因组研究，包括大量谱系，特别强调跨免疫和代谢基因的多基因家族进化。与之前的分析一致，我们发现 APOBEC3 和 MHC-I 基因家族的谱系特异性扩增，以及促炎性 PYHIN 基因家族的缺失。我们推断不止1，000 蝙蝠特有的基因丢失，包括参与调节炎症小体通路的基因，如上皮防御受体、自然杀伤基因复合物和干扰素-γ 诱导通路。基因集富集分析表明，蝙蝠体内丢失的基因参与了针对病原体相关分子模式和损伤相关分子模式的防御反应。基因家族进化和选择分析表明，与其他哺乳动物相比，蝙蝠在先天和适应性免疫系统方面已经进化出基本的功能差异，具有增强抗病毒免疫反应同时抑制炎症信号的潜力。此外，代谢基因经历了与向植物性饮食的趋同转变相关的反复扩张。我们的分析支持这样的假设，即在飞行的同时，