Meet your viral ancestors – how bornaviruses have been infiltrating our genomes for 40 million years

Cast your mind back 40 million years and think about your ancestors. You’re probably picturing creatures that looked like a bit like today’s monkeys, but they’re only part of your family tree. To see your other ancestors, you’d have to whip out an imaginary microscope. Meet your great-great-great-etc-grandviruses.

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The human genome is littered with the remains of viruses that, in ages past, integrated their genes into the DNA of our ancestors. They became a permanent fixture, passed down from parent to child. Today, these “endogenous retroviruses“, or ERVs, make up around 8% of our genome. They’re a living fossil record of prehistoric plagues.

Until recently, scientists thought that the only viruses to have left such a legacy were the retroviruses, a group that includes modern members such as HIV and hepatitis B. But they are no longer alone. Masayuki Horie and Tomoyuki Honda from Osaka University have found that another viral dynasty, the bornaviruses, have repeatedly inveigled their way into the genomes of mammals. They’re found in humans, the great apes, elephants, rodents and many more. Those that lurk amid our genes have been our partners in evolution for at least 40 million years.

Almost all of these hidden sequences match the N gene of the most famous bornavirus – BDV or Borna disease virus. As a result, Horie and Honda christened their newfound sequences as EBLNs (or “endogenous Borna-like N” elements). We carry four such sequences but many others exist. A scan of over 234 genomes revealed that EBLNs are found in all manner of mammals, including chimps, gorillas, orang-utans, macaques, lemurs, bushbabies, African elephants, hyraxes, ground squirrels, mice, rats, guinea pigs, bats and opossums.

Most of these EBLNs are the result of independent invasions, at different points in the history of mammal evolution. Squirrels have only carried their EBLNs for less than 10 million years but our own genetic passengers have been riding and co-evolving with us for over 40 million years.

The vast majority of them apparently do nothing. Over the course of evolution, they have decayed into functionless ‘pseudogenes’, now nothing more than genetic garbage. They’re like the books on the shelf that you never read, acting as a historical record without doing anything useful. But not all of them – two of the human EBLNs are still active. They’re still transcribed into RNA, and they still produce working proteins. One of these even interacts with other proteins that we’ve inherited from our more direct primate ancestors.

We don’t yet know what these proteins do. But their very existence suggests that our ancestors co-opted their viral interlopers and put them to use, domesticating them to act as productive parts of our own cells. In this way, bornaviruses have provided raw material for the evolution of mammals.

This process depends on the viral genes jumping into the right place. Enter the wrong site, and they could cause significant harm by disrupting existing genes. Indeed, there’s some tantalising (albeit controversial) evidence suggests that this goes on today and contributes to mental health problems in humans.

BDV targets the neurons of a wide variety of birds and mammals, causing weird movements and behaviour. tT was actually named for the town of Borna, Germany, where a killer epidemic of cavalry horses in 1885 led to its discovery. In humans, the virus has been linked (albeit inconclusively) to various psychiatric disorders including schizophrenia. It’s possible that BDV creates disease-causing mutations by inserting its genes into the wrong parts of our genomes.

Horie and Honda have certainly demonstrated that modern BDV can perform the same act of genetic infiltration that its ancestors clearly pulled off. They infected either lab-grown cells or mice with BDV and found that chunks of the virus’s DNA had been integrated into that of its host. These additions look a lot like the ‘fossil’ EBLN sequences found in our own genomes. Whether this could lead to disease is another question, and one for future research.

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Reference: Horie et al. 2010. Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature 463: 84-88. http://doi.org/10.1038/nature08695

Feschotte. 2010. Bornavirus enters the genome. Nature 436: 39.

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