Deciphering the Origin of DNA Viruses (Replication-Associated Parvo-NS1) That Infect Vertebrates from Invertebrate-Infecting Viruses

DNA replication is a standard and essential function among DNA viruses; however, this functional domain's common ancestor, origin, and evolutionary path in invertebrate- and vertebrate-infecting viruses are not yet fully understood. Here, we present evidence, using a combination of phylogenetic relationships, coevolution, and CLANS (cluster analysis of sequences) analysis, that the parvo-NS1 domain (nonstructural protein NS1, DNA helicase domain) of these DNA viruses that infect vertebrates potentially originated from the invertebrate (Platyhelminthes) parvo-NS1 domain of parvovirus-related sequences (PRSs). Our results suggest that papillomaviruses and the parvovirus subfamilies Densovirinae and Hamaparvovirinae DNA helicase evolved directly from the Platyhelminthes NS1 domain (PRSs). Similarly, the parvovirus subfamily Parvovirinae NS1 domain displayed evolutionary heritage from the PRSs through Hamaparvovirinae. Further, our analysis also clarified that herpesviruses and adenoviruses independently obtained the parvo-NS1 domain from Dependoparvovirus (Parvovirinae). Furthermore, virus-host coevolution analysis revealed that the parvovirus NS1 domain has coevolved with hosts, from flatworms to humans, and it appears that the papillomavirus may have obtained the DNA helicase during the early stages of parvovirus evolution and later led to the development of the DNA helicase of adomavirus and polyomavirus. Finally, herpesviruses and adenoviruses likely inherited the parvo-NS1 domain from Dependoparvovirus in the later stages of evolution. To the best of our knowledge, this is the first evolutionary evidence to suggest that the DNA helicase of viruses that infect vertebrates originated from the invertebrate PRSs. IMPORTANCE DNA replication of DNA viruses is an essential function. This allows DNA replication of viruses to form virus particles. The DNA helicase domain is responsible for this primary function. This domain is present in parvoviruses, papillomaviruses, polyomaviruses, herpesviruses, and adenoviruses. But little is known about the common ancestor, origin, and evolutionary path of DNA helicase in invertebrate- and vertebrate-infecting viruses. Here, we report the possibility of the origin of DNA viruses (DNA helicase) infecting vertebrates from Platyhelminthes (invertebrate) PRSs. Our study established that the parvovirus subfamily Parvovirinae NS1 domain displayed evolutionary heritage from the Platyhelminthes PRSs through Hamaparvovirinae. Furthermore, our study suggests that the papillomavirus DNA helicase may have evolved in the early stages of parvovirus evolution and then led to the development of the adomavirus and polyomavirus. Our study suggests that the herpesviruses and adenoviruses likely inherited the parvo-NS1 domain through gene capture from Dependoparvovirus in the later stages of parvovirus evolution in their hosts.