Identification of “Missing Link” Families of Small DNA Tumor Viruses

Adenoviruses, papillomaviruses, parvoviruses and polyomaviruses are collectively known as small DNA tumor viruses. Although it has long been recognized that small DNA tumor virus oncoproteins and capsid proteins show a variety of structural and functional similarities, it is unclear whether these similarities reflect descent from a common ancestor, convergent evolution, horizontal gene transfer among virus lineages, or repeated acquisition of genes from host cells. We report the discovery of fourteen new members of an emerging fourth family of small DNA tumor viruses, the . Cell culture-based expression of adomavirus open reading frames showed that the virion structural proteins of adomaviruses are homologous to those of adenoviruses. The search for adomaviruses unexpectedly revealed the existence of a previously unrecognized family of animal DNA viruses that are distantly similar to virophages and other polinton-like viruses of unicellular eukaryotes. Members of the new “adintovirus” family encode retrovirus-like integrase proteins and adenovirus-like DNA polymerase and virion structural proteins. Adintovirus sequences were found in genomics datasets for all major groups of animals, including terrestrial vertebrates. Analysis of the gene content of adintoviruses supports a model in which small DNA tumor viruses descended from more complex adintovirus-like ancestors through gene-loss and horizontal gene transfer events occurring hundreds of millions of years ago.