New research published in the Proceedings of the National Academy of Sciences reveals an ongoing war between bits of virus DNA in the genome of koalas. And this war might well help to save ailing populations of the iconic marsupial, as well as helping to unlock the mysteries of so called “junk DNA”.
As parasites, single-strand viruses known as “retroviruses” can’t do much for themselves. They have a genome that they can’t use or replicate on their own. Instead they invade and hijack host cells. Once inside, they insert their entire genome into the host DNA, becoming what is known as a “provirus”. The host’s cellular machinery then makes viral proteins and genomes which are spread to other hosts.
And so, on goes the process of infection.
However, sometimes retroviruses insert themselves into the germline – that is, into sex cells, such as sperm and ova. This means that the entire genome of the virus is passed from one host generation to the next, and often these become permanent features of the host DNA. These are known as “endogenous retroviruses” (ERVs).
ERVs are all over the place, mostly found as inert junk DNA. They make up to 8% of the human genome, are found far and wide in various vertebrates and are generally thought to be harmless. However, no one really knows how these disease-causing agents transition from violent killers to peaceful tenants.
An international team of researchers has now shed light on this process by investigating a transition that is currently happening within the genome of the Australian koala (Phascolarctos cinereus).
“In humans, the youngest known endogenous retrovirus groups are around five million years old,” says author Alfred Roca, of the Department of Animal Sciences at the University of Illinois in the US.
“That makes it very hard to tell what happened. But the koala is one of the few species known to have an ongoing invasion of the germline by a retrovirus.”
The koala ERV is hasn’t fully changed its lifestyle, being less than 50,000 years old, and still has some of its killer habits. This has led to cancers and a suppression of the host’s immune system, leaving it open to secondary infection: chlamydia, for example, is widespread in mainland koala populations.
“We think the pressure for external viruses is to make lots of copies of themselves and infect more individuals,” Roca explains.
“But once the virus becomes part of the host germline, the pressure is going to be for it to leave the host alone because the host is needed to reproduce the sequence. It has to play nice or otherwise it disappears. The question is how does this process take place?”
Surprisingly, another long-term resident of the koala genome may hold the answer. An ancient and unrelated ERV is helping to fight back by inserting itself into the genome of the new tenant, leading to selective deactivation of its coding regions. Instead of producing proteins or new genomes, it is beginning to produce, well, nothing.
“We might have found evidence for a molecular defence mechanism of hosts against new retroviral attacks, mediated by more ancient retroviral elements,” says first author Ulrike Löber of the Leibniz Institute for Zoo and Wildlife Research in Berlin, Germany.
Even with such help, it will be hundreds of thousands of years before the new ERV becomes neighbourly.
In the meantime, the research is helping to determine which elements of the invader’s DNA are dangerous, which aids in the search for a vaccine. It also sheds light on the mystery of how deadly retroviral pathogens become inert junk DNA, a process that last happened to us five million years ago.
Stephen Fleischfresser is a lecturer at the University of Melbourne's Trinity College and holds a PhD in the History and Philosophy of Science.
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