Willemsen, A. | bioRxiv Science

bioRxiv2018

Origin and evolution of papillomavirus (onco)genes and genomes

Papillomaviruses (PVs) are ancient viruses infecting vertebrates, from fish to mammals. Although the genomes of PVs are small and show conserved synteny, PVs display large genotypic diversity and ample variation in the phenotypic presentation of the infection. Most PVs genomes contain two small early genes E6 and E7. In a bunch of closely related human PVs, the E6 and E7 proteins provide the viruses with oncogenic potential.\n\nThe recent discoveries of PVs without E6 and E7 in different fish species place a new root on the PV tree, and suggest that the ancestral PV consisted of the minimal PV backbone E1-E2-L2-L1.\n\nBayesian phylogenetic analyses date the most recent common ancestor of the PV backbone to 424 million years ago (Ma). Common ancestry tests on extant E6 and E7 genes indicate that they share respectively a common ancestor dating back to at least 184 Ma. In AlphaPVs infecting primates, the appearance of the E5 oncogene 53-58 Ma concurred with i) a significant increase in substitution rate, ii) a basal radiation, and iii) key gain of functions in E6 and E7. This series of events was instrumental to build the extant phenotype of oncogenic human PVs.\n\nOur results assemble the current knowledge on PV diversity and present an ancient evolutionary timeline punctuated by evolutionary innovations in the history of this successful viral family.

evolutionary biology↗

bioRxiv2018

Genome plasticity in Papillomaviruses and de novo emergence of E5 oncogenes

The clinical presentations of papillomavirus (PV) infections come in many different flavors. While most PVs are part of a healthy skin microbiota and are not associated to physical lesions, other PVs cause benign lesions, and only a handful of PVs are associated to malignant transformations linked to the specific activities of the E5, E6 and E7 oncogenes. The functions and origin of E5 remain to be elucidated. These E5 ORFs are present in the genomes of a few polyphyletic PV lineages, located between the early and the late viral gene cassettes. We have computationally assessed whether these E5 ORFs have a common origin and whether they display the properties of a genuine gene. Our results suggest that during the evolution of Papillomaviridae, at least four events lead to the presence of a long non-coding DNA stretch between the E2 and the L2 genes. In three of these events, the novel regions evolved coding capacity, becoming the extant E5 ORFs. We then focused on the evolution of the E5 genes in AlphaPVs infecting humans. The sharp match between the type of E5 protein encoded in AlphaPVs and the infection phenotype (cutaneous warts, genital warts or anogenital cancers) supports the role of E5 in the differential oncogenic potential of these PVs. In our analyses, the best-supported scenario is that the five types of extant E5 proteins within the AlphaPV genomes may not have a common ancestor. However, the chemical similarities between E5s regarding amino acid composition prevent us from confidently rejecting the model of a common origin. Our evolutionary interpretation is that an originally non-coding region entered the genome of the ancestral AlphaPVs. This genetic novelty allowed to explore novel transcription potential, triggering an adaptive radiation that yielded three main viral lineages encoding for different E5 proteins, and that display distinct infection phenotypes. Overall, our results provide an evolutionary scenario for the de novo emergence of viral genes and illustrate the impact of such genotypic novelty in the phenotypic diversity of the viral infections.

evolutionary biology↗