An ancient endogenous DNA virus in the human genome

The genomes of eukaryotes preserve a striking diversity of ancient viruses in the form of endogenous viral elements (EVEs). Study of this genomic fossil record provides insights into the diversity, origin and evolution of viruses across geological timescales. In particular, Mavericks have emerged as one of the oldest groups of viruses infecting vertebrates (≥419 My). They have been found in the genomes of fish, amphibians and non-avian reptiles but had been overlooked in mammals. Thus, their evolutionary history and the causes of their demise in mammals remain puzzling questions. Here, we conduct a detailed evolutionary study of two Maverick -like integrations found on human chromosomes 7 and 8. We performed a comparative analysis of the integrations and determined their orthology across placental mammals (Eutheria) via the syntenic arrangement of neighbouring genes. The integrations were absent at the orthologous sites in the genomes of marsupials and monotremes. These observations allowed us to reconstruct a time-calibrated phylogeny and infer the age of their most recent common ancestor at 268.61 (199.70–344.54) My. In addition, we estimate the age of the individual integrations at ~105 My which represent the oldest non-retroviral EVEs found in the human genome. Our findings suggest that active Mavericks existed in the ancestors of modern mammals ~172 My ago (Jurassic Period) and potentially to the end of the Early Cretaceous. We hypothesise Mavericks could have gone extinct in mammals from the evolution of an antiviral defence system or from reduced opportunities for transmission in terrestrial hosts.