Laboratory of RNA Viruses, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University, 606-8507 Kyoto, Japan.
Laboratory of RNA Viruses, Department of Mammalian Regulatory Network, Graduate School of Biostudies, Kyoto University, 606-8507 Kyoto, Japan.
Proc Natl Acad Sci U S A. 2021 May 18;118(20). doi: 10.1073/pnas.2026235118.
Although viruses have threatened our ancestors for millions of years, prehistoric epidemics of viruses are largely unknown. Endogenous bornavirus-like elements (EBLs) are ancient bornavirus sequences derived from the viral messenger RNAs that were reverse transcribed and inserted into animal genomes, most likely by retrotransposons. These elements can be used as molecular fossil records to trace past bornaviral infections. In this study, we systematically identified EBLs in vertebrate genomes and revealed the history of bornavirus infections over nearly 100 My. We confirmed that ancient bornaviral infections have occurred in diverse vertebrate lineages, especially in primate ancestors. Phylogenetic analyses indicated that primate ancestors were infected with various bornaviral lineages during evolution. EBLs in primate genomes formed clades according to their integration ages, suggesting that bornavirus lineages infected with primate ancestors had changed chronologically. However, some bornaviral lineages may have coexisted with primate ancestors and underwent repeated endogenizations for tens of millions of years. Moreover, a bornaviral lineage that coexisted with primate ancestors also endogenized in the genomes of some ancestral bats. The habitats of these bat ancestors have been reported to overlap with the migration route of primate ancestors. These results suggest that long-term virus-host coexistence expanded the geographic distributions of the bornaviral lineage along with primate migration and may have spread their infections to these bat ancestors. Our findings provide insight into the history of bornavirus infections over geological timescales that cannot be deduced from research using extant viruses alone, thus broadening our perspective on virus-host coevolution.
虽然病毒已经威胁到我们的祖先数百万年了，但史前病毒的流行情况在很大程度上是未知的。内源性 bornavirus 样元件（EBL）是古老的 bornavirus 序列，源自病毒信使 RNA，这些 RNA 经反转录并插入动物基因组中，很可能是通过逆转录转座子完成的。这些元件可用作分子化石记录，以追踪过去的 bornavirus 感染。在这项研究中，我们系统地鉴定了脊椎动物基因组中的 EBL，并揭示了近 1 亿年来 bornavirus 感染的历史。我们证实，古代 bornavirus 感染发生在多种脊椎动物谱系中，尤其是在灵长类动物祖先中。系统发育分析表明，灵长类动物的祖先在进化过程中感染了多种 bornavirus 谱系。灵长类动物基因组中的 EBL 根据其整合年龄形成了进化枝，这表明感染灵长类动物祖先的 bornavirus 谱系在时间上发生了变化。然而，一些 bornavirus 谱系可能与灵长类动物祖先共存，并经历了数千万年的重复内源性化。此外，与灵长类动物祖先共存的 bornavirus 谱系也在内源性蝙蝠祖先的基因组中发生了内源性化。这些蝙蝠祖先的栖息地曾被报道与灵长类动物祖先的迁徙路线重叠。这些结果表明，长期的病毒-宿主共存扩大了 bornavirus 谱系的地理分布，伴随着灵长类动物的迁徙，并可能将其感染传播给这些蝙蝠祖先。我们的研究结果为地质时间尺度上的 bornavirus 感染史提供了新的认识，这是仅通过研究现存病毒无法推断的，从而拓宽了我们对病毒-宿主共同进化的认识。
