NEXT time you have a cold, rather than cursing, maybe you should thank the virus for making your skin. Genes borrowed from viruses seem to give cells the ability to grow into tissues and organs, and even reproduce sexually. Without these genes, animals could not have evolved beyond simple blobs of cells.
Our cells often need to fuse with other cells, making big cells with multiple nuclei. They do this with the help of proteins on their outer surfaces that stick the cell's walls together and then break them open, so the insides can mix. This mixing is essential for the production of most organs – such as muscles, skin and bone – and even for reproduction, when eggs and sperm fuse. For instance, fused cells form barriers in the placenta that prevent harmful chemicals crossing into the fetus, and internal tubes like blood vessels are also made of fused cells.
But despite its importance, nobody knows how cell fusion evolved. That is partly because the proteins responsible are hard to spot. Only two types of cell fusion protein have been identified so far. The first was syncytin, found in 2000, which is essential for the formation of the human placenta. The gene for syncytin came from a virus (Nature, doi.org/c53gpz).
Then in 2002, a second protein called EFF-1 was found. It helps form the skin of the roundworm Caenorhabditis elegans, which biologists often study because it is so simple (Developmental Cell, doi.org/cd7mcf). By 2007 it was clear that EFF-1 was one of a family of similar proteins, called FF proteins, after a similar protein called AFF-1 was also found.
Now Felix Rey of the Pasteur Institute in Paris, France, has found that the FF family of cell fusion proteins also comes from viruses.
Rey's team figured out the 3D structure of the EFF-1 protein using crystallography and X-ray diffraction – the same kinds of techniques that were used to determine the structure of DNA in the 1950s. The structure of EFF-1 resembles that of a protein made by viruses, and the active part – which does the work of linking one cell to another – is virtually identical. Viruses use the protein to rip open the membrane of a cell, which they can then infect. In the worms, both cells must have the protein before they can fuse, but the protein still works in a similar way. He presented his results at the Lorne Conference on Protein Structure and Function in Australia last month, and they have been accepted by the journal Cell.
Since EFF-1 is so similar to the viral protein, the gene for it almost certainly came from a virus that infected one of the worm's ancestors, says Rey. That is not unprecedented: the human genome is littered with DNA that slipped in when viruses infected a cell of an ancestor. But few of these bits of code are known to have important functions.
While EFF-1 has only been studied in C. elegans, Rey says many other organisms may use the same protein. Since syncytin is also viral, all the cell fusion proteins found so far are from viruses. Does that mean early animals picked up all these proteins through viral infections?
"That's the gut feeling we have," says Fasseli Coulibaly from Monash University in Melbourne, Australia. "It's the most enticing hypothesis but as scientists we need to look into it. If this is true, that's a huge advance."
It is plausible that all cell fusion stems from viral genes slipping into our genome, says Elizabeth Chen of Johns Hopkins University in Baltimore, Maryland. "But the jury is still out." Right now her team is trying to find the protein responsible for cell fusion in muscle tissue. It is too early to tell if it came from a virus.
The findings so far suggest a pattern, says Rey. If cell fusion proteins came from several sources, you wouldn't expect the first two found to be from viruses.
If viruses really did gift us cell fusion, then they are responsible for complex multicellular life, says Coulibaly. Cells could have clumped together into clusters on their own, but without the ability to fuse they could not have evolved into anything advanced like sponges, let alone humans.
"Before cells can make something like skin or a digestive tract in nematodes – or as soon as you are thinking muscles or bones in mammals – usually you need some kind of fusion," says Coulibaly. "If it's proved, it could be a Nobel prize."
Rey goes even further. He speculates that viruses may be responsible for the very existence of multicellular organisms. Viruses come and go between different cells, exchanging genetic information between them. "This makes me think that viruses have contributed enormously to the communication between cells, and to the appearance of multicellular organisms on Earth," Rey says.