Paleovirology: Studying Bird Genomes Uncovers a Mesozoic Virus

The genome of a Mesozoic paleovirus reveals the evolution of hepatitis B viruses

Authors:

1. Alexander Suh (a,c)
2. Jürgen Brosius (a)
3. Jürgen Schmitz (a)
4. Jan Ole Kriegs (a,b)

Affiliations:

a. Institute of Experimental Pathology (ZMBE), University of Münster, Von-Esmarch-Straße 56, D-48149 Münster, Germany

b. LWL-Museum für Naturkunde, Westfälisches Landesmuseum mit Planetarium, Sentruper Straße 285, D-48161 Münster, Germany

c. Present address: Department of Evolutionary Biology, Evolutionary Biology Centre, Uppsala University, Norbyvägen 18D, SE-752 36 Uppsala, Sweden

Abstract:

Paleovirology involves the identification of ancient endogenous viral elements within eukaryotic genomes. The evolutionary origins of the reverse-transcribing hepatitis B viruses, however, remain elusive, due to the small number of endogenized sequences present in host genomes. Here we report a comprehensively dated genomic record of hepatitis B virus endogenizations that spans bird evolution from greater than 82 to less than 12.1 million years ago. The oldest virus relic extends over a 99% complete hepatitis B virus genome sequence and constitutes the first discovery of a Mesozoic paleovirus genome. We show that Hepadnaviridae are greater than 63 million years older than previously known and provide direct evidence for coexistence of hepatitis B viruses and birds during the Mesozoic and Cenozoic Eras. Finally, phylogenetic analyses and distribution of hepatitis B virus relics suggest that birds potentially are the ancestral hosts of Hepadnaviridae and mammalian hepatitis B viruses probably emerged after a bird–mammal host switch. Our study reveals previously undiscovered and multi-faceted insights into prehistoric hepatitis B virus evolution and provides valuable resources for future studies, such as in-vitro resurrection of Mesozoic hepadnaviruses.