Past Pandemics Are in Our Genes
What koalas can teach us about human evolution and disease.
Photo by Torsten Blackwood/AFP/Getty Images.
To understand what it means to be human, you have to understand koalas. Or, to be more precise, you have to understand how they are dying from a bizarre viral outbreak that has been raging for the past 150 years or so. The koalas are now going through something our ancestors experienced 31 times over the past 60 million years. And those ancient viral outbreaks have helped to make us who we are today.
Australian biologists discovered the koala outbreak in 1988. They were examining the blood of a koala dying of leukemia when they came across a virus infecting its white blood cells. The koala retrovirus, as it is now known, made its hosts sick in much the same way the feline leukemia virus sickens cats. It inserted its genes into host immune cells, which then produced new viruses. The infection also caused the cells to replicate at a frenzied rate. Once the scientists had found the koala retrovirus in one koala, they looked for it in others, and they soon found it all over the koala’s range—the entire eastern side of Australia.
Koalas had long been known to have terrible health. One survey estimated that leukemia and lymphoma were responsible for up to 80 percent of koala deaths. The discovery of the koala retrovirus made sense of this cancer epidemic. It also explained why koalas were getting devastated by chlamydia, a sexually transmitted bacterium. By turning koalas’ immune systems cancerous, the virus was leaving the koalas open to infection by other pathogens.
Scientists who went rummaging through koala skins in museums found genes from the retrovirus as far back as the mid-1800s, but that still makes it a fairly young outbreak. To figure out where the koala retrovirus came from, scientists have compared its genes to those of other species of viruses. One of the most similar viruses to it infects the grassland mosaic-tailed rat of Australia. The virus may well have been carried from the rats to the koalas by a mosquito or a tick.
Once the koalas picked up the retrovirus, they began to spread it among themselves. After young koalas are weaned but before they start dining on eucalyptus leaves, they feed on their mother’s feces—feces that may be laden with koala retroviruses. The epidemic appears to have started in northern Australia, where today the virus is ubiquitous. Since then, it has spread southward, even jumping to islands off the coast of Australia—presumably in the guts of mosquitos.
As it spreads, the koala retrovirus is doing something else: It is genetically merging with the koala itself. In many koalas, the virus’ genes aren’t present just in the immune cells. The koalas carry the virus genes in every cell of their bodies, from their vestigial tails to their snub noses and in every organ in between. When these koalas reproduce, they pass the viral DNA along with their own to their offspring.
These koala-virus hybrids are the result of a peculiar sort of infection. Every now and then, the koala retrovirus ends up infecting an egg or a sperm. It inserts its genes into the DNA of the host cell, as it normally does. But instead of churning out new viruses that infect other cells, the infected sex cell does something else: It becomes a new koala. As a fertilized, virus-carrying egg divides and grows into an embryo, the koala retrovirus DNA is copied into every new cell. And when that virally infused koala is born and grows up and reproduces, it passes the virus down as well. In many cases, the inherited virus DNA still has the potential to make new viruses that can infect other koalas and trigger cancer in them.
The koala retrovirus continues to spread today, attacking the last uninfected populations. In years to come, it will kill off many more animals while inserting itself into the DNA of the survivors. It’s likely that at some point every koala left on Earth will carry the virus’ genes. And in future generations, those genes will gradually mutate and lose their ability to make new viruses. Eventually, the koala retrovirus will become extinct. All that will remain will be its imprisoned DNA.
This ongoing merging makes the koala retrovirus different than just about any other virus on Earth today known to science. But it is hardly unique in the history of life. When scientists look at the genomes of humans and other animals, they see stretches of DNA that bear indisputable hallmarks of viruses. In many cases, two closely related species will share the same viral DNA at the same spot in their genomes. That shared remnant of an ancient parasite tells scientists that the virus infected the common ancestor of both species. We share viral DNA with other primates, indicating that our common ancestors were invaded by viruses starting some 60 million years ago.
Aris Katzourakis of the University of Oxford has tallied up all of the invasions of retroviruses into the genomes of our ancestors. His latest total is 31. Each of those invasions may well have caused a devastating outbreak akin to what retroviruses are doing to koalas today—perhaps spreading an immune-crushing cancer that nearly brought our early primate ancestors to extinction.
Eventually, these outbreaks ended, and the viruses became trapped in their hosts. But they didn’t lose all their viral powers. They could still parasitize their host’s genome. Sometimes a cell would make an extra copy of the viral genes and then insert them back elsewhere in its genome. As a result, our 31 viral invasions gave rise to 100,000 separate chunks of virus DNA. Altogether, they make up at least 8 percent of the human genome.
In their lingering twilight, our endogenous retroviruses can still be dangerous to our health. When a new copy of their DNA gets inserted into our genome, it can disrupt an essential gene. And cancer cells often switch the virus genes back on, probably using them to the cancer’s own advantage. Some viral proteins help tumors escape the immune system’s notice, for example.
On the other hand, evolution has domesticated some of these virus genes for our own benefit. One virus gene makes a protein that’s essential for placentas to join to the uterus wall. And we use other virus genes to fight off free-living viruses. Some virus proteins are produced in our brains, although no one knows what, if anything, they are doing there.
It’s been millions of years since we last acquired a new endogenous retrovirus. The outbreaks that helped build the human genome are ancient history. But that doesn’t mean that a 32nd retrovirus won’t worm its way into our genome. New retroviruses—such as HIV, which jumped from chimpanzees to humans in the early 1900s—infect our species fairly often. We can’t predict which virus species will slip into eggs and sperm and provide us with the next piece of the human genome, but here is one fact that’s pretty unsettling to ponder: If you put a koala retrovirus in a dish with human cells, it can easily infect them. Koalas may not just be a guide to our past. Perhaps they will be a part of our future.