Excavating New Facts from Ancient Hepatitis B Virus Sequences

Abstract

Recently, Muhlemann et al. (2018) and Krause-Kyora et al. (2018) discovered 15 ancient Hepatitis B virus (aHBV) sequences dating back to the Neolithic age (NA) and the Bronze age (BA). Being published simultaneously, neither of these studies could include sequences from the other for analyses. In the present research, aHBV sequences from these studies were collective re-analysed with reference to a comprehensive database comprising extant HBV diversity to understand their relatedness and role in the evolution of extant HBV diversity.Present analyses revealed several interesting findings on distribution, dispersal, phylogenetic and recombinational relatedness of ancient HBV to extant genotypes, which were not recognized previously. Several interesting recombination patterns were observed, which corroborated well with ancient human migration, shown by the human genetic studies. Present analyses suggest that comparable to the replacement of the Neolithic European farmer associated Y chromosome haplogroups by haplogroups associated with the steppe people during Steppe migration, HBV genotype associated with the early Neolithic European farming cultures was also replaced by the ancestral HBV genotype A probably carried by the migrating steppe people, and a variant of this genotype is the prevalent HBV genotype in contemporary European populations. Additionally, based on recent literature, this research also indicates that HBV genotype divergence estimates proposed by Muhlemann et al., and others cannot sufficiently explain distribution of certain extant HBV genotypes. Hence, an alternative possibility to explain long distance and trans-oceanic distribution of phylogenetically related HBV genotypes was reviewed and discussed in the light of currently available knowledge. Through this manuscript, novel and important findings of the present analyses are communicated.Rapid technological advancements in sequencing technologies and computational tools over the last few decades have enabled sequencing and reconstruction of highly divergent genomes including ancient pathogen genomes (Spyrou et al., 2019). This has established the field of 'ancient pathogen genomics', which is helping us better understand their origin, evolution, epidemiology apart from revealing their interaction with hosts (Spyrou et al., 2019). Recently, Mühlemann and colleagues reported 12 complete or partial ancient Hepatitis B virus (aHBV) genome sequences isolated from archaeological human remains dating back to ca. 4500 years. Concurrently, Krause-Kyora and colleagues, reported three additional aHBV sequences, two of which were more ancient (ca. 5000-7000 years) than Mühlemann et al. For the first time, these two studies provided direct evidence for human HBV infection since Neolithic and Bronze ages. However, being published simultaneously, neither of these studies could include sequences from the other for comparative analyses.Additionally, two other previous studies provided aHBV from recent past (ca. 400-500 years) (Pattersson et al., 2018;Bar-gal...

The impact of evolutionary processes in shaping the genetics of complex traits in East Asia and Europe: a specific contribution from Denisovan and Neanderthal introgression

“…Neanderthal and Denisovan admixture have been previously associated with the diversity of innate immunity genes in modern humans 20,65,66 . Neanderthal introgression was previously linked to immunological phenotypes, rheumatoid arthritis 27 and chronic hepatitis B 67 , and Graves' disease 27 in EUR and EAS. Denisovan introgression was linked to several immune processes, e.g., antiviral immune response, HIV-1 DNA integration, and cytokine signaling 66 .…”