Poster Presentation Society for Molecular Biology and Evolution Conference 2016

Co-evolution of Hepatitis B Virus subgenotype C4 and Indigenous Australians for at least 53,000 years (#615)

Lilly Yuen 1 , Margaret Littlejohn 1 , Jane Davies 2 3 , Sarah Bukulatjpi 2 4 , Paula Binks 2 , Kathy Jackson 1 , Josh Davis 3 5 , Steven Tong 2 3 , Stephen Locarnini 1
  1. Victorian Infectious Diseases Reference Laboratory, Doherty Institute, Melbourne, VIC, Australia
  2. Menzies School of Health Research and Charles Darwin University, Darwin, NT, Australia
  3. Department of Infectious Diseases, Royal Darwin Hospital, Darwin, NT, Australia
  4. Ngalkanbuy Clinic, Galiwin’ku, NT, Australia
  5. John Hunter Hospital, Newcastle, NSW, Australia

Hepatitis B is an ancient human infection characterised by slow disease progression. It has been proposed HBV evolved with modern humans following migration out of Africa and diverged into 10 genotypes (A-J). Indigenous Australians have the oldest continuous living culture outside of Africa. However, entry time and likely access point into Sahul remain controversial. We have shown the strain of HBV infecting Aboriginal people in Northern Territory of Australia is a novel subgenotype HBV/C4. These people are located over vast distances with no known epidemiological connections. We hypothesized HBV/C4 entered Sahul with these First Australians. We obtained genome sequences of 59 HBV/C4 and 216 other publicly available HBV sequences for recombination, time divergence and ancestral state reconstruction analyses, and found HBV/C4 is a recombinant virus, predominantly genotype C (80%) with a genotype J surface (S) gene (20%). Phylogenies showed the HBV/C component clustered with other human HBV/Cs, while the S-gene of HBV/C4 and HBV/J clustered with South-east Asian (SEA) (Sunda) non-human primate HBVs. Time to most recent common ancestor (tMRCA) for HBV/C4 and HBV/J, potentially when the C-J recombination event took place, was inferred ~71K years. tMRCA of all HBV/C4 was ~53K, indicating this unique strain has been in Australia for this long, overlapping the estimated arrival date of Indigenous Australians based on archaeological evidence. Ancestral state reconstruction analysis inferred Daly River was where HBV/C4 originally entered Sahul. Given the Wallace Line separates the fauna between Asia and Australia ecozones, the recombination of HBV/C and HBV/J to generate HBV/C4 would most likely has to have occurred on Sunda. Based on the data obtained, we propose HBV/C4 originated on Sunda ~71kya, has been in Australia for at least 53K years, and likely was brought in by the ancestors of Indigenous Australians entering via the Daly River region.