Human jumping gene found in poxvirus genome

A primate-specific gene has been found to have 'jumped' into a human-infecting virus from the pox family.

BC200 is a noncoding gene found exclusively in humans and other primates, where it is particularly active in neurons. Like almost half of the human genome, BC200 originated from a transposable element (TE), a 'jumping gene' that could copy and paste itself in new locations within and between genomes. It was then repurposed for a new function within primate cells, a 'domestication' process normally associated with TEs losing their mobility. New investigations now show that BC200 has in fact 'jumped' from human cells into the genome of a benign poxvirus at least twice during modern human history.

'Genes that come from transposable elements and that are repurposed for cellular functions are typically no longer transposable,' said Professor Cedric Feschotte from Cornell University, New York, a senior author of the study published in Science. 'BC200 was itself created from a mobile element but has retained its mobility and yet it is also clearly serving a cellular function. Somehow evolution hasn't been able to untangle these two things.'

The retrotransposon (a type of TE) that gave rise to BC200 integrated into the genome of the common ancestor of anthropoid primates around 40 million years ago. Although BC200's exact role remains unclear, it is thought to participate in the regulation of protein synthesis within neurons, and it is expressed at low levels in germline cells. Its aberrant expression has also been reported in various conditions, including cancer and Alzheimer's disease.

TEs that remain transpositionally active – that is, which can still move and insert themselves into new locations in the genome – can cause disease. However, these events, when present in the germline, can also create genetic diversity and play an important role in evolution, for example by leading to new ways to control or assemble genes.

To investigate BC200 transpositional activity, the team used specialised software to screen for TE-related sequences in the genomes of viruses from the pox family. This revealed two BC200-like elements within the genome of molluscum contagiosum virus (MCV), a poxvirus that only infects humans and causes harmless skin papules. Additional analyses showed that these sequences likely resulted from two independent 'jumping events' whereby BC200 integrated itself within the MCV genome during modern human history.

'To our knowledge, our study documents the first instance of a retrotransposon having naturally integrated into a human virus,' said the authors.

Next, the researchers examined whether they could find evidence of BC200 transpositional activity within primate genomes. Their analyses showed that, indeed, BC200 insertions could be detected within the human germline, as well as across the genomes of all anthropoid primates.

The existence of a 'domesticated' TE that is important for cellular function yet remains transpositionally active opens new avenues for investigation into the evolutionary trade-offs at the root of these characteristics. The team also hopes to explore further the role of BC200 within MCV, and whether the virus may be using these sequences to its advantage when infecting human cells.