Dating the Origin and Dispersal of Hepatitis B Virus Infection in Humans and Primates

         The origin of hepatitis B virus (HBV) infection in humans and other apes remains largely  unresolved.  Understanding  the  origin  of  HBV  is  crucial  because  it  provides  a framework for studying the burden, and subsequently the evolution, of HBV pathogenicity with  respect  to  changes in  human  population  size and  life expectancy.  To  investigate this controversy, we examined the relationship between HBV phylogeny and genetic diversity of modern  humans,  investigated  the  timescale  of  global  HBV  dispersal  and  tested  the hypothesis  of  HBV-human  co-divergence.  We  find  that  the  global  distribution  of  HBV genotypes  and  subgenotypes  are  consistent  with  the  major  prehistoric  modern  human migrations. We calibrate the HBV molecular clock using the divergence times of different indigenous human populations based on archaeological and genetic evidence, and show that HBV  jumped  into  humans  around  33,600;  95%  Higher  Posterior  Density:  22,000-47,100 years ago (estimated substitution rate: 2.2 × 10-6; 95% Higher Posterior Density: 1.5-3.0 × 10-6substitutions/site/year).  This  coincides  with  the  origin  of  modern  non-African  humans. Crucially,  the  most  pronounced  increase  in  the  HBV  pandemic  correlates  with  the  global population increase over the last 5,000 years. We also show that the non-human HBV clades in  orang-utans  and  gibbons  resulted  from  cross-species  transmission  events  from  humans that occurred no earlier than 6,100 years ago .Conclusion: Our study provides, for the first time,  an  estimated  timescale  for  the  HBV  epidemic  that  closely  coincides  with  dates  of human  dispersals,  supporting  the  hypothesis  that  HBV  has  been  co-expanding  and  co-migrating with human populations for the last 40,000 years. 点击下载此文件