There are previous claims that smallpox was present in Egypt, India and China over thousands of years, but the emergence of the causative agent, variola virus (VARV), is still unclear. In addition, the authors were interested in how widespread immunisation carried out in the 20th century led to viral evolution. Some previous molecular-clock-based studies have suggested that key events in VARV evolution only occurred in the last two centuries, which doesn’t make sense in the historical context. The authors captured, sequenced and reconstructed a draft genome of an ancient strain of VARV from a Lithuanian child mummy dating between 1643 and 1665, close to the time of several documented European epidemics. They found that, when compared to vaccinia virus, this old strain of VARV had the same gene loss as 20th century VARVs, suggesting that this loss of gene function occurred before 1650. The mummy sequence was basal to all currently sequenced strains of VARV on phylogenetic trees. Molecular-clock analyses uncovered a strong clock-like structure, suggesting that the timescale of smallpox evolution is more recent than previously thought, with diversification of major lineages only occurring in 18th and 19th centuries when modern vaccination occurred.
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