Genomic fossils reveal adaptation of non-autonomous pararetroviruses driven by concerted evolution of noncoding regulatory sequences

The interplay of different virus species in a host cell after infection can affect the adaptation of each virus. Endogenous viral elements, such as endogenous pararetroviruses (PRVs), have arisen from vertical inheritance of viral sequences integrated into host germline genomes. As viral genomic fossils, these sequences can thus serve as valuable paleogenomic data to study the long-term evolutionary dynamics of virus–virus interactions, but they have rarely been applied for this purpose. All extant PRVs have been considered autonomous species in their parasitic life cycle in host cells. Here, we provide evidence for multiple non-autonomous PRV species with structural defects in viral activity that have frequently infected ancient grass hosts and adapted through interplay between viruses. Our paleogenomic analyses using endogenous PRVs in grass genomes revealed that these non-autonomous PRV species have participated in interplay with autonomous PRVs in a possible commensal partnership, or, alternatively, with one another in a possible mutualistic partnership. These partnerships, which have been established by the sharing of noncoding regulatory sequences (NRSs) in intergenic regions between two partner viruses, have been further maintained and altered by the sequence homogenization of NRSs between partners. Strikingly, we found that frequent region-specific recombination, rather than mutation selection, is the main causative mechanism of NRS homogenization. Our results, obtained from ancient DNA records of viruses, suggest that adaptation of PRVs has occurred by concerted evolution of NRSs between different virus species in the same host. Our findings further imply that evaluation of within-host NRS interactions within and between populations of viral pathogens may be important.感染宿主细胞后，不同病毒物种间的相互作用会影响各自的适应性。内源性病毒元件（endogenous viral elements），例如内源性副逆转录病毒（endogenous pararetroviruses, PRVs），源自整合到宿主生殖系基因组中的病毒序列的垂直遗传。作为病毒基因组化石，这类序列可作为宝贵的古基因组数据，用于研究病毒间相互作用的长期进化动态，但目前极少被应用于该研究方向。此前所有现存的PRVs均被认为是在宿主细胞内营寄生生活的自主型病毒物种。本研究为多种存在病毒活性结构缺陷的非自主型PRV物种提供了实证——这类病毒曾频繁侵染古老的禾本科宿主，并通过病毒间的相互作用完成适应性演化。我们通过对禾本科基因组中的内源性PRVs开展古基因组分析，发现这些非自主型PRV物种，要么与自主型PRV形成潜在的偏利共生伙伴关系，要么彼此间形成潜在的互利共生伙伴关系。这类伙伴关系通过两个伙伴病毒共享基因间区域的非编码调控序列（noncoding regulatory sequences, NRSs）得以建立，并通过伙伴间NRS的序列同质化过程进一步维持和演化。值得注意的是，我们发现频繁的区域特异性重组而非突变选择，是导致NRS序列同质化的主要机制。本研究基于病毒古DNA记录所得出的结果表明，PRVs的适应性演化是通过同一宿主内不同病毒物种间NRS的协同进化实现的。本研究结果进一步暗示，对病毒病原体种群内部及种群间的宿主内NRS相互作用开展评估，或具有重要意义。