Abstract
The complete genome sequences of two strains of variola virus (VARV) sampled from human smallpox specimens present in the Czech National Museum, Prague, were recently determined, with one of the sequences estimated to date to the mid-19th century. Using molecular clock methods, the authors of this study go on to infer that the currently available strains of VARV share an older common ancestor, at around 1350 AD, than some recent estimates based on other archival human samples. Herein, we show that the two Czech strains exhibit anomalous branch lengths given their proposed age, and by assuming a constant rate of evolutionary change across the rest of the VARV phylogeny estimate that their true age in fact lies between 1918 and 1937. We therefore suggest that the age of the common ancestor of currently available VARV genomes most likely dates to late 16th and early 17th centuries and not ~1350 AD.
Highlights
Pajer et al [1] recently characterized two human smallpox specimens from the Czech NationalMuseum in Prague, retrieving the complete genomes of the causative variola virus (VARV) in both cases.The first specimen, V1588, consisted of a 10 cm2 piece of skin with pock lesions, while the second, V563, comprised an intact forearm and foot from a child displaying the distinctive smallpox rash
We query the estimated ages of V1588 and V563 and the time-scale of smallpox evolution presented by Pajer et al [1], as more recent studies have utilized V1588 and V563 to date the antiquity of VARV [3]
This discrepancy is apparent in a maximum likelihood (ML) tree of 45 complete VARV genomes in which V563 and V1588 occupy anomalous positions (Figure 1a)
Summary
Pajer et al [1] recently characterized two human smallpox specimens from the Czech NationalMuseum in Prague, retrieving the complete genomes of the causative variola virus (VARV) in both cases.The first specimen, V1588, consisted of a 10 cm2 piece of skin with pock lesions, while the second, V563, comprised an intact forearm and foot from a child displaying the distinctive smallpox rash. The authors of this study estimated the rate and time-scale of VARV evolution, suggesting that the available VARV strains share a common ancestor that existed around 1350 AD.
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