Reliable timescale inference of HBV genotype A origin and phylodynamics

Gianguglielmo Zehender, Valentina Svicher, Elena Gabanelli, Erika Ebranati, Carla Veo, Alessandra Lo Presti, Eleonora Cella, Marta Giovanetti, Linda Bussini, Romina Salpini, Claudia Alteri, Alessia Lai, Elisabetta Tanzi, Carlo Federico Perno, Massimo Galli, Massimo Ciccozzi

Research output: Contribution to journalArticlepeer-review


The worldwide distributed Hepatitis B virus (HBV) genotype A is classified into three subgenotypes, and one quasi-subgenotype. The majority of HBV-A subgenotypes are widespread in Africa and in ethnic groups that have relatively recently emigrated from African countries, whereas HBV-A2 is highly prevalent among subjects at high risk for sexual exposure to HBV in north-western Europe and the USA.The aim of this study was to reconstruct the origin and dispersion of HBV-A subgenotypes on a reliable timescale using short-term calibration based on heterochronous sampling for HBV-A2, and long-term calibration based on historical data for the other subgenotypes. To this aim, we analysed 113 newly characterised HBV-A isolates with 247 reference sequences retrieved from a public database. The phylodynamic reconstruction was performed by a Bayesian framework. The common ancestor of the currently circulating A subgenotypes was placed in west-central Africa a mean 1057. years ago. The genotype diverged into two main clades at the beginning of the 13th century: one including all of the west-central African quasi-subgenotypes and the other corresponding to subgenotype A1, originating in east Africa and further segregating into two main subclades: an "African" and a "cosmopolitan" clade. It is likely that the slave trade was the main source the spread of cosmopolitan HBV-A1, which was exported to Asia in the 17th century as a result of Arab or Portuguese trade, and to Latin America in the 18th centuries through the trans-Atlantic slave trade. The origin of the currently circulating A2 strains dates back to the first decades of the 20th century, and the evolutionary demography analysis suggests an exponential growth of infections, between 1970s and the mid-1990s. In conclusion, the very different epidemiological and evolutionary histories of HBV-A subgenotypes justify the use of different calibration approaches to reconstruct their reciprocal phylodynamics.

Original languageEnglish
Pages (from-to)361-369
Number of pages9
JournalInfection, Genetics and Evolution
Publication statusPublished - Mar 14 2015


  • HBV genotype A
  • HBV subgenotype A1
  • HBV subgenotype A2
  • Hepatitis B virus
  • Molecular clock calibration
  • Phylogeography

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Molecular Biology
  • Microbiology
  • Infectious Diseases
  • Microbiology (medical)


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