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’.

天花是由天花病毒 (VARV) 引起的一种高致病性、高死亡率的疾病，直到 1980 年成功根除天花，才对全球人类健康造成重大威胁。尽管之前已公布了历史和现代天花病毒基因组，但其过去的传播和多样性仍然存在争论了。为了了解欧洲历史和现代天花病毒遗传变异的天花病毒进化史，我们对来自英格兰的一个详细描述的十八世纪病例（标本 P328）的天花病毒基因组进行了测序。在我们的系统发育分析中，新的基因组介于现代菌株和来自立陶宛的另一种历史菌株之间，支持了先前关于现代早期欧洲比二十世纪具有更大多样性的说法。我们的分析还通过确认十七世纪左右的较晚日期，解决了之前关于现代菌株和历史菌株之间共同祖先的争议。总体而言，我们的结果表明历史基因组有助于更好地解析过去的天花病毒多样性，并强调来自世界各地的此类历史基因组对于进一步了解天花及相关疾病的进化历史的价值。

本文是主题“从古代生物分子洞察健康和疾病”的一部分。