Journal Article Preprint Epublish
PubMed: 42327129 DOI: 10.64898/2026.06.05.730483
Reconciling fast Hepatitis B evolutionary rates with ancient co-divergence.
bioRxiv
Authors: Philippe Lemey, Xiang Ji, Bram Vrancken, Magdalini Bletsa, Pratyusa Datta, Liana Eleni Kafetzopoulou, Jonathon Mifsud, Guy Baele, Mahmoud Reza Pourkarim, Livia Patrono, Sebastien Calvignac-Spencer, Ludovic Orlando, Paul Bastide, Stephane Guindon, Darren Martin, Marc A Suchard
Abstract
Estimating evolutionary rates and divergence times for hepatitis B virus (HBV) has long been complicated by conflicting calibration approaches and extensive rate variation. To unlock the full potential of ancient and modern HBV genomic data, we develop a Bayesian mixed-effects molecular clock model that accounts for various sources of rate variation including time-dependent rate decay. Our analyses reveal a pronounced decline in evolutionary rates over time, reconciling HBV divergence estimates with human migration events across both deep and more recent timescales. We show that HBV spread into Europe through both Neolithic farming expansions and later steppe migrations, paralleling patterns proposed for Indo-European language origins. Phylogeographic reconstructions suggest that the Neolithic-associated lineage dispersed at approximately 1 km/year, consistent with archaeological estimates, while genotype D expanded during the Bronze Age at an almost threefold higher rate, plausibly driven by technological innovations underlying steppe expansions. Historical overlap between these lineages facilitated recombination, giving rise to genotype E, which has become a dominant HBV genotype in Africa. These findings demonstrate that ancient viral genomes, when analyzed with models capturing complex rate dynamics, provide a powerful lens on human prehistory and the processes shaping pathogen diversity.
MeSH
Genotype, Grassland, Hepatitis B, Hepatitis