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近北极地区蝙蝠的超长寿命与DNA病毒驱动的适应性

Extensive longevity and DNA virus-driven adaptation in nearctic bats.

作者信息

Vazquez Juan M, Lauterbur M Elise, Mottaghinia Saba, Bucci Melanie, Fraser Devaughn, Gray-Sandoval Genavieve, Gaucherand Léa, Haidar Zeinab R, Han Melissa, Kohler William, Lama Tanya M, Le Corf Amandine, Loyer Clara, Maesen Sarah, McMillan Dakota, Li Stacy, Lo Johnathan, Rey Carine, Capel Samantha Lr, Singer Michael, Slocum Kathleen, Thomas William, Tyburec Janet Debelak, Villa Sarah, Miller Richard, Buchalski Michael, Vazquez-Medina Jose Pablo, Pfeffer Sébastien, Etienne Lucie, Enard David, Sudmant Peter H

机构信息

Department of Integrative Biology, University of California, Berkeley, Berkeley, CA USA.

These authors contributed equally.

出版信息

bioRxiv. 2024 Nov 27:2024.10.10.617725. doi: 10.1101/2024.10.10.617725.

Abstract

The genus is one of the largest clades of bats, and exhibits some of the most extreme variation in lifespans among mammals alongside unique adaptations to viral tolerance and immune defense. To study the evolution of longevity-associated traits and infectious disease, we generated near-complete genome assemblies and cell lines for 8 closely related species of . Using genome-wide screens of positive selection, analyses of structural variation, and functional experiments in primary cell lines, we identify new patterns of adaptation contributing to longevity, cancer resistance, and viral interactions in bats. We find that bats have some of the most significant variation in cancer risk across mammals and demonstrate a unique DNA damage response in primary cells of the long-lived . We also find evidence of abundant adaptation in response to DNA viruses - but not RNA viruses - in and other bats in sharp contrast with other mammals, potentially contributing to the role of bats as reservoirs of zoonoses. Together, our results demonstrate how genomics and primary cells derived from diverse taxa uncover the molecular bases of extreme adaptations in non-model organisms.

摘要

该属是蝙蝠中最大的进化枝之一,在哺乳动物中展现出一些寿命方面最极端的差异,同时对病毒耐受性和免疫防御具有独特的适应性。为了研究与长寿相关的性状和传染病的进化,我们为8种与之密切相关的物种生成了近乎完整的基因组组装和细胞系。通过全基因组阳性选择筛选、结构变异分析以及原代细胞系中的功能实验,我们确定了有助于蝙蝠长寿、抗癌和病毒相互作用的新适应模式。我们发现,蝙蝠在哺乳动物中具有一些最显著的癌症风险差异,并在长寿蝙蝠的原代细胞中表现出独特的DNA损伤反应。我们还发现,与其他哺乳动物形成鲜明对比的是,该属及其他蝙蝠对DNA病毒(而非RNA病毒)有丰富的适应性,这可能有助于蝙蝠作为人畜共患病宿主的作用。总之,我们的结果表明,来自不同分类群的基因组学和原代细胞如何揭示非模式生物中极端适应的分子基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e1b4/11600882/b968bd3eebe6/nihpp-2024.10.10.617725v2-f0001.jpg

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