Reconstructing prehistoric viral genomes from Neanderthal sequencing data

Abstract

AbstractDNA viruses that produce persistent infections have been proposed as potential causes for the extinction of Neanderthals. Here we searched for DNA viral genomes in sequencing reads of Neanderthal genome projects by mapping to references of Adenovirus, Herpesvirus and Papillomavirus, which are double stranded DNA viruses that establish lifelong latency. Reconstructed ancient viral genomes exhibited conserved segments with significant similarity to extant viral genomes. Variable positions were identified in coding regions and revealed substantial divergence to any extant closest relatives. Sequencing reads mapped to references showed typical deamination patterns of ancient DNA, suggesting that contamination with modern viral DNA is unlikely. These ancient viral genomes showed divergence corresponding with the age of these samples (≈50,000 years) and the viral evolutionary rates (10-5to 10-8substitutions/site/year). Variable regions reveal Neanderthal adaptive signatures, such as nonsynonymous substitutions in viral surface proteins that interact with receptors on host cells. Conserved regions here identified can be used as PCR targets for amplification of viral genomes from Neanderthal isolated DNA, in future experiments, that might close low coverage gaps in the assemblies for accurate reconstruction of these viral paleogenomes. Mapping Neanderthal and signatures of anatomically modern humans (AMH) in these viruses is essential to establish whether Neanderthals might have acquired these infections from invading modern human populations, as proposed to explain the extinction of Neanderthal upon contact with AMH.