Comparative analysis reveals the long-term co-evolutionary history of parvoviruses and vertebrates [preprint]

Abstract

Parvoviruses (family Parvoviridae) are small, non-enveloped DNA viruses that infect a broad range of animal species. Comparative studies, supported by experimental evidence, show that many vertebrate species contain sequences derived from ancient parvoviruses embedded in their genomes. These ‘endogenous parvoviral elements’ (EPVs), which arose via recombination-based mechanisms in infected germline cells of ancestral organisms, constitute a form of ‘molecular fossil record’ that can be used to investigate the origin and evolution of the parvovirus family. Here, we use comparative approaches to investigate 198 EPV loci, represented by 470 EPV sequences identified in a comprehensive in silico screen of 752 published vertebrate genomes. We investigated EPV loci by constructing an open resource that contains all of the data items required for comparative sequence analysis of parvoviruses and uses a relational database to represent the complex semantic relationships between them. We used this standardised framework to implement reproducible comparative phylogenetic analysis of combined EPV and virus data. Our analysis reveals that viruses closely related to contemporary parvoviruses have circulated among vertebrates since the Late Cretaceous epoch (100-66 million years ago). We present evidence that the subfamily Parvovirinae, which includes ten vertebrate-specific genera, has evolved in broad congruence with the emergence and diversification of major vertebrate groups. Furthermore, we infer defining aspects of evolution within individual parvovirus genera - mammalian vicariance for protoparvoviruses (genus Protoparvovirus), and inter-class transmission for dependoparvoviruses (genus Dependoparvovirus) - thereby establishing an ecological and evolutionary perspective through which to approach analysis of these virus groups. We also identify evidence of EPV expression at RNA level and show that EPV coding sequences have frequently been maintained during evolution, adding to a growing body of evidence that EPV loci have been co-opted or exapted by vertebrate species, and especially by mammals. Our findings offer fundamental insights into parvovirus evolution. In addition, we establish novel genomic resources that can advance the development of parvovirus-related research - including both therapeutics and disease prevention efforts - by enabling more efficient dissemination and utilisation of relevant, evolution-related domain knowledge.