What Hepatitis B tells us about the migration of ancient humans

The viral genetics of Hepatitis B is helping to trace the history and movement of Australia’s first people back at least 51 thousand years

By Associate Professor Steven Tong and Dr Margaret Littlejohn, Doherty Institute, University of Melbourne and the Royal Melbourne Hospital

It’s now widely accepted that continental Sahul – the combined landmass of Australia, New Guinea and Tasmania – was settled very early in human history, as anatomically modern humans moved from Africa using what archaeologists refer to as the Southern Dispersal Route.

But the exact entry point and timing of this ancient human migration is a question that has plagued scientists and archaeologists.

The initial migration route for HBV/C4 into the Tiwi Islands / East Arnhem (orange arrow). Picture: Dr Lillli Yuen/Doherty

That is until now. And unexpectedly it’s the modern day hepatitis B virus, known as HBV, providing us with some interesting answers.

In a collaboration between the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and Menzies School of Health Research, our team of researchers analysed the genome sequences of the virus to deduce that the mainland Aboriginal population separated from other early humans at least 51 thousand years ago and possibly entered the country near the Tiwi Islands in northern Australia, supporting archaeological findings.

This means these humans made their way to our ancient supercontinent, which was eventually split by rising sea levels, and they, together with the virus they carried, were isolated from the rest of the world.

The discovery, published in Molecular Biology and Evolution, was made as an offshoot of the Characterising Hepatitis B in Indigenous Australians thRough Molecular epidemiology (CHARM) study, which the Menzies began in 2010.

Chronic HBV infection is endemic in the Australian Aboriginal population and is an important cause of morbidity and mortality as a result of liver disease and cancer.

As part of our clinical work in the Northern Territory, we were seeing many Aboriginal patients with Hepatitis B at the Royal Darwin Hospital clinic, often with very advanced disease.

In caring for these patients, we began investigating what type of HBV was causing these infections and collected HBV samples from people living in over 30 communities across the Northern Territory.

The team collected HBV samples from people living in over 30 communities across the Northern Territory. Picture: Dr Jay Roberts

Amazingly, we found that the HBV isolated from these Aboriginal Australians is a unique strain called HBV/C4 - which is not found anywhere else in the world.

Not only was every sample we examined carrying HBV/C4, but when we started looking at the HBV/C4 DNA sequences, we noted that the virus sequences had very strong geographical connections to the communities we visited.

In the same way that human genome sequences are used to trace ancient human migration, we hypothesised that we could use modern-day viral genomes to estimate the movement of the people that have carried these viruses over many generations.

Importantly, HBV is usually transmitted from mother to child around the time of birth, and therefore the ancestry of HBV, is likely to reflect the ancestry of those carrying the virus.

To establish this, our team used cutting-edge evolutionary analyses of the HBV DNA sequences together with archaeological fossil and human genome data.

We found that the precursor of the modern HBV/C4 virus entered Australia more than 51 thousand years ago.

By combining data of evolutionary rates of the virus and the location of communities in which patients now live, our analyses suggested that there was a more than 60 per cent probability that the HBV/C4 virus entered Australia through either the Tiwi Islands or East Arnhem regions in Australia’s far north.

There’s a more than 60 per cent probability that the HBV/C4 virus entered through either the Tiwi Islands or East Arnhem regions. Picture: Wikimedia

HBV/C4 then separated into two groups; one in the northwest region, and the other in the central eastern region of the Northern Territory. Strikingly, the two groups share a similar geographical distribution to the two main divisions of Aboriginal Australian languages spoken in Australia today.

One of our study’s other co-authors, Professor Josh Davis, Senior Principal Research Fellow at Menzies, says the discovery has generated great interest with Aboriginal research partners and patients - raising the profile of Hepatitis B in communities. Many have asked to find out more about Hepatitis B and how they can be tested and treated.

We also worked with a Senior Aboriginal Health Practitioner, Sarah Bukulatjpi, a co-author on the study, to dispel some of the silence and shame many feel about the virus.

Our study is endorsed by an Indigenous Reference Group made up of members representing six different remote communities from across the Northern Territory and established by the Menzies Hepatitis B Research Program.

We also ensured that these results were fed back to the main communities where samples came from. In our work, it is best practice to let communities know about the results of any studies they’re involved in and to provide opportunities to comment on the findings and their appropriateness to be published.

Our research team is now proceeding with programs to better understand the severity of HBV/C4 infections in Aboriginal Australians, and to drive the elimination of Hepatitis B in the Northern Territory.

Using viral genetics to help tell the story of Australia’s first people is a novel approach – and the fact the virus is so old helps to add to the evidence that Aboriginal people have been in Australia for a long, long time.

Picture: Getty Images