Variola virus genome sequenced from an eighteenth-century museum specimen supports the recent origin of smallpox

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’.

An Update of Orthopoxvirus Molecular Evolution

“…Akhmeta virus and Alaskapox virus form separate branches from the rest of the Old World orthopoxviruses on the species phylogram of this genus, whereas Abatino clusters with ectromelia virus (ECTV). Progress in molecular methods has made it possible to study the genomic sequences of ancient VARV [2,[12][13][14][15][16]. All these expanded data allow us to re-evaluate the molecular evolution of orthopoxviruses and more reliably determine their time of origin and the rate of genetic variation.…”

“…In each case, this allowed for a more accurate dating of the evolutionary history of VARV [2,12,14]; the rates of the VARV genome evolution were calculated to be (7-9) × 10 −6 substitutions/site/year [12] and (3.7-6.5) × 10 −6 [2]. Later, dating for the Czech specimens was revised and they were estimated to be 1937 and 1933 under a relaxed clock [13,16]. The corrected rate of evolution of VARV complete genome sequences, with the exception of strains from the Czech Republic, was (7.0-10.0) × 10 −6 substitutions/site/year [16].…”

Insights into health and disease from ancient biomolecules

“…They also discuss putative animal reservoirs including pinnipeds, of which they have identified 13 individuals with potential tuberculosis lesions. While most ancient biomolecular research on the history and spread of pathogens has focused on bacteria, Ferrari et al [21] sequenced the genome of a variola virus recovered from an eighteenth century English case to provide insight into the origins of twentieth century smallpox lineages as well as the impact on their diversity by vaccination which became widespread after the end of the eighteenth century.…”

Mortality, migration and epidemiological change in English cities, 1600–1870

“…This pattern is consistent with the emergence or introduction of a novel smallpox strain in seventeenth century Europe ( Carmichael and Silverstein, 1987 ). It is also likely that control measures including inoculation and vaccination exerted substantial selective pressures on the subsequent evolution and radiation of modern smallpox strains ( Ferrari et al, 2020 ).…”