Abstract
Smallpox, caused by the variola virus (VARV), was a highly virulent disease with high mortality rates causing a major threat for global human health until its successful eradication in 1980. Despite previously published historic and modern VARV genomes, its past dissemination and diversity remain debated. To understand the evolutionary history of VARV with respect to historic and modern VARV genetic variation in Europe, we sequenced a VARV genome from a well-described eighteenth-century case from England (specimen P328). In our phylogenetic analysis, the new genome falls between the modern strains and another historic strain from Lithuania, supporting previous claims of larger diversity in early modern Europe compared to the twentieth century. Our analyses also resolve a previous controversy regarding the common ancestor between modern and historic strains by confirming a later date around the seventeenth century. Overall, our results point to the benefit of historic genomes for better resolution of past VARV diversity and highlight the value of such historic genomes from around the world to further understand the evolutionary history of smallpox as well as related diseases.This article is part of the theme issue ‘Insights into health and disease from ancient biomolecules’.
Highlights
Smallpox was a highly contagious and lethal disease [1,2]
A whole-genome alignment was calculated based on the newly sequenced and computationally reconstructed genome of sample P328, 44 modern and three historic publicly available variola virus (VARV) genomes [37,39,70,71,72], as well as eight additional Orthopoxvirus genomes [72,73,74,75,76,77] and a horsepox virus genome reconstructed from a vaccine manufactured in 1902 AD [78]
To computationally reconstruct the genome of an eighteenth century AD VARV strain, we collected a sample from a museum specimen with a known diagnosis of smallpox, specimen RCSHC/P 328 from the Hunterian collection at the Royal College of Surgeons of England
Summary
Smallpox was a highly contagious and lethal disease [1,2]. Before its eradication— declared in 1980 AD [1]—smallpox caused several large-scale epidemics that spanned centuries with remarkably high death rates [1,2]. We followed the recommendations of the World Health Organization (WHO) for handling DNA from VARV samples [55] with the following exceptions: (i) owing to the highly fragmented and damaged nature of the aDNA [53,54], no autoclaving step of the sample and its byproducts was performed; (ii) temporary retention of greater than 20% of the VARV genome in a non-infectious and fragmented form with full extraction of sample and no remaining original material; and (iii) handling of the ancient VARV DNA in our dedicated laboratory at the University of Zurich. As there are discrepancies about the dating of samples V563 and V1588 [37,38], we used the Bayesian framework BEAST 2.5.2 [81] to estimate the tip dates for the historic genomes based on the time intervals given in the electronic supplementary material, table S2 These intervals cover the years from the original publication [37] and the corresponding comment [38]. See the electronic supplementary material, files S2 and S3
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