By Meghan Sullivan
What is it about viruses that so easily captures our attention? With the teeth mostly taken out of bacterial infections by the advent of penicillin and parasites a rare and mostly exotic concern, viruses remain one nemesis that we often struggle to treat. Unlike complex bacteria and parasites, viruses are little more than genetic material wrapped up in a vessel designed to take its blue prints to the next host. Once in a host, viruses inject their genetic material into cells and take over the cellular machinery to carry out their lifecycles. Imagine terrorists sneaking into a Ford factory and using the assembly lines to crank out WMDs. Infected cells eventually die, but not before triggering immune responses (coughing, sneezing, etc) that aide their spread to the next host.
Taken starkly, viruses execute an elegant life cycle. If the aim of life is to pass on one’s genetic material, viruses have succeeded by reducing themselves to only genetic material, relying on other organisms for the messy business of replicating and spreading. The only way to make the process more streamlined would be to cut out the effort of budding, replicating, and finding its next host.
Which, it seems, viruses have also done.
Called human endogenous retroviruses (HERVs), some viruses have slipped their genetic material into our genome, inserting themselves between host genes or in the long stretches of inaptly named “junk” DNA. Over the course of evolution, these genetic stowaways were passed down to the host’s offspring right alongside genes for blue eyes and attached earlobes. Millions of years later, we find remnants of the viruses encountered by our ancestors written in our DNA like graffiti in a bathroom stall. HERVs comprise as much as 8% of the human genome and some may have integrated into our genomes as long ago as 60-70 million years ago.
Considering the vast changes our genome has undergone in the past 70 million years (by comparison, the human-chimpanzee split occurred only 6 million years ago) it makes sense that the HERVs fossilized in our genome have also been changing. HERVs, like the rest of our genome, acquire DNA mutations at a low but consistent rate. Scientists are able to estimate when a HERV integrated – and by extension, when it was last infectious – by comparing mutations in long terminal repeat (LTR) sequences, stretches of DNA that flank the viral genes like book ends. At the time of integration, these regions are identical, but the longer the HERV has been in the genome, the more mutations the LTRs acquire. By comparing the differences in LTRs flanking HERVs, scientists can estimate how long a HERV has been in the genome.
Previously, the youngest HERVs were estimated to be 800,000 years old. For a recent paper in the journal PLoS ONE that explored how recently HERVs were actually circulating as viruses, Aashish Jha, a University of Chicago graduate student in the Department of Human Genetics and former member of Douglas Nixon‘s lab at UCSF, looked for recent integrations into the human genome. Using a genome browser at UCSC, Jha and colleagues tracked all the human-specific, full-length HERVs at a particular place in the human genome. Interestingly, one HERV called k106 didn’t fit the normal timeline.
“It looked interesting because it did not have any mutations in its LTRs,” Jha said.
This was an unusual find, as the age of most HERVs insures at least a few mutations that would aid in dating it. Using genetic information from 51 ethnically diverse individuals, Jha and colleagues were able to estimate that the k106 HERV integrated between 92 and 100 thousand years ago, making it one of the youngest HERVs ever identified.
“This time period is exactly the time modern humans were emerging,” Jha pointed out, “So someone was infected and, given that it was a small population size, it rapidly became fixed in the genome. Then humans moved out of Africa…so even though the virus is new we find it fixed in every human population.”
Having identified this recently integrated, human-specific HERV, it’s possible to gain insight on the ways HERVs have affected the course of our development. LTRs flanking HERVs contain signals that control when and where genes are turned on and off. Placing these viral signals in front of host genes could impact how and when they are expressed and, in some cases, lend an advantage to the individuals possessing it.
“There are multiple ways they [affect evolution],” Jha said.
“One is positively: LTRs can drive the expression of nearby genes and at the right time, right place, might help someone. Let’s say a HERV integrates in front of an immune gene…and over-expresses it in some individuals which helps an individual tackle disease.”
Not all effects are so sunny: while some HERVs appear as no more than crumbled ruins of the viruses they once were, others can still produce viral proteins, possibly contributing to some autoimmune conditions. Perhaps even more sinister is the idea that HERVs are simply using our genomes as incubators until their hunting grounds have been repopulated.
“What [HERVs] can do is infect the genome…. and stay there quietly for thousands to millions of years. And suddenly they jump back,” Jha said. “For the HERV, it would be perfectly ideal…the host population stabilizes and then the HERV comes back.” If the virus had simply rampaged through the host population, causing disease, it could lead to extinction of the host. “But if it endogenizes, then it gets a chance to calm down.”
However, the connection between HERVs and disease is not well established, whereas other effects on the genome are more widely accepted. One HERV protein called Syncytin is believed to have been instrumental in the evolution of the placenta and, by extension, the ascent of mammals. The effects HERVs have had on our development are far from well cataloged, but the identification of recent integrations such as k106 – the first HERV identified as having integrated after the rise of modern man – will help us understand some leaps in our evolution as well as the threats that may be contained within our own cells.
Photo: Electron micrograph of a negatively stained human papilloma virus (NIH-Visuals Online/Wikimedia Commons)
Jha, A., Nixon, D., Rosenberg, M., Martin, J., Deeks, S., Hudson, R., Garrison, K., & Pillai, S. (2011). Human Endogenous Retrovirus K106 (HERV-K106) Was Infectious after the Emergence of Anatomically Modern Humans PLoS ONE, 6 (5) DOI: 10.1371/journal.pone.0020234