An Adagio for Viruses, Played Out on Ancient DNA

Studies of ancient DNA have transformed our understanding of human evolution. Paleogenomics can also reveal historic and prehistoric agents of disease, including endemic, epidemic, and pandemic pathogens. Viruses—and in particular those with single- or double-stranded DNA genomes—are an important part of the paleogenomic revolution, preserving within some remains or environmental samples for tens of thousands of years. The results of these studies capture the public imagination, as well as giving scientists a unique perspective on some of the more slowly evolving viruses which cause disease. In this review, we revisit the first studies of historical virus genetic material in the 1990s, through to the genomic revolution of recent years. We look at how paleogenomics works for viral pathogens, such as the need for careful precautions against modern contamination and robust computational pipelines to identify and analyze authenticated viral sequences. We discuss the insights into virus evolution which have been gained through paleogenomics, concentrating on three DNA viruses in particular: parvovirus B19, herpes simplex virus 1, and smallpox. As we consider recent worldwide transmission of monkeypox and synthetic biology tools that allow the potential reconstruction of extinct viruses, we show that studying historical and ancient virus evolution has never been more topical.