September 16, 2021

I, Science

The science magazine of Imperial College

Reza Rezaei Javan investigates syncytins - viral genes that are essential for our survival

1000px-PlacentaMany individuals think of viruses as harmful organisms that invade, infect and even kill. But the reality is very different as a virus has now been credited with making human life possible.

According to an article in Discover Magazine, Boston-based scientists made an incredible discovery in 2000 (published in Nature). While examining the human genome, they encountered a curious gene now known as syncytin.  Syncytin serves to encode a protein that is found only in placenta-based cells. The cells that create syncytin are situated in one location: at the point where the uterus and placenta meet and fuse to form a layer of cells known as the syncytiotrophoblast. This cellular layer is critical as it enables the human fetus to obtain nutrients from the mother’s body.  Syncytin is also found in other primates, like gorillas and chimpanzees. This discovery led scientists to conclude that the genetic change that resulted in the formation of syncytin gene must have occurred at an early point in primate evolution, impacting an ancestor that’s common to humans, gorillas and chimpanzees.

Gray37The scientists discovered that syncytin is produced as a precursor to the formation of the cellular layer that allows for a fusion of the placenta and uterus. But what makes syncytin even more incredible is the finding that it didn’t arise from a mammalian gene: syncytin arose from a virus. So what originally started as a viral gene designed to produce proteins that would fuse the host’s cells together, thereby allowing the virus to spread with greater ease, now serves to connect mother and child. Quite simply, syncytin is critical and without it, human life could never form.

Viruses have the ability to make changes at the genetic level. Scientists have found that viruses have been invading and shaping what would ultimately become the human genome for millions of years.  Most of these viruses altered the genetic code by invading sperm or eggs. Once inside these cells, the viruses target the DNA and integrate their own viral DNA into the host’s DNA. If the sperm or egg goes on to produce a viable organism, the viral gene can be inherited from one generation to the next.

The net effect has been quite significant over time, as it’s believed that a whopping 8 percent of human DNA — over 100,000 known fragments — can be attributed to viruses. And while most think of viruses as harmful organisms, some gave rise to viral genes in our genome that serve to generate proteins. Some of these viral genes, like syncytin, have been found to be essential to human survival.

Model of the Syncytin 2 protein

Following the 2000 discovery of syncytin, French virologist Thierry Heidmann went on to discover another syncytin gene. Called syncytin 2, this viral gene serves to suppress the mother’s immune system to prevent her body from attacking and rejecting her baby’s tissues as it would a foreign body.

Heidmann’s discoveries didn’t end there. His team of researchers discovered that, contrary to the initial findings, syncytin is not just found in the Great Apes, but is present in other mammals, including mice and rabbits. Like humans and primates, the mouse was found to have two varieties of syncytin, called syncytin A and syncytin B. An additional variety of syncytin, called syncytin-Ory1, was discovered in rabbits in 2009.

In one study, the syncytin A gene was disabled in a mouse and the embryo died in a matter of days due to its inability to form a syncytiotrophoblast. This served to further emphasize the important role of viruses in shaping the mammalian genome.
Heidmann’s studies into the syncytin gene didn’t end with the rabbits. The virologist ultimately discovered that the carnivoran group of mammals — including dogs, cats, hyenas, tigers, panda bears and seals — all possess a variety of syncytin called syncytin-Car1. This led Heidmann to conclude that the virus altered the carnivoran genome sometime after the carnivorans split from other mammal groups approximately 85 million years ago. Over time, it’s believed a process of natural selection occurred and ultimately, syncytin became essential.

Heidmann’s discoveries paint an incredible story, as these findings have some interesting implications. It appears that on six different occasions, the virus responsible for the syncytin gene infected different mammals. Six slightly different versions of syncytin gene arose, and all six would prove to have a critical role in the reproductive process. The research continues into other mammals, as scientists attempt to determine whether they also have a variant of the syncytin gene.

Reza Rezaei Javan  is studying for an MSc in the  Molecular Biology & Pathology of Viruses
Images: Placenta; Syncytiotrophoblast; Syncytin 2 (Wikimedia Commons)