Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, today infects a majority of adults globally1, yet no ancient HSV-1 genomes have yet been published. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups2, 3 has suggested that the virus co-diverged with anatomically modern humans migrating out of Africa4, although a much younger origin has also been proposed5. The lack of ancient HSV-1 genomes, high rates of recombination, and high mobility of humans in the modern era have impeded the understanding of HSV-1s evolutionary history. Here we present three full ancient European HSV-1 genomes and one partial genome, dating to between the 3rd and 17th century CE, sequenced to up to 9.5x with paired human genomes up to 10.16x. These HSV-1 strains fall within modern Eurasian diversity. We estimate a mean mutation rate of 7.6 x 10-7 - 1.13 x 10-6 for non-African diversity leading to an estimated age of sampled modern Eurasian diversity to 4.68 (3.87 - 5.65) kya. Extrapolation of these rates indicate the age of sampled HSV-1 to 5.29 (4.60-6.12 kya, suggesting lineage replacement coinciding with late Neolithisation and implicating Bronze Age migrations6 in the distribution of HSV-1 through Eurasia.