So far on Gene of Interest, we’ve explored what can go wrong: how genes are lost; terrible diseases caused by small mutations; tiny errors that have massive consequences. But that’s only half the picture. With all this chaos, how did humanity end up with a working genome in the first place? Where do genes come from? The likely answer: many many happy accidents, but I’d like to examine one – without it none of us would have been born – this week’s gene of interest: syncytin (ERVW-1).
Humans are mammals – we’re hairy, warm-blooded, and the ladies have boobs – and we’re part of the largest subset of mammals, placentals. All placentals have the unique ability to carry their developing young inside a womb until fully developed. A baby needs nutrients to develop, so an unborn placental has to collects nutrients from its mother’s bloodstream, but it has to do so carefully. Not only can mother and child have different blood types (so direct connection of blood vessels would be a huge no-no), to the mother’s immune system, the developing baby is a foreign invader. The mother’s white blood cells are adapted to slip themselves between other cells to reach any part of the body, so baby has to create a barrier to protect itself from mommy [1].
Studies of Embryos by Leonardo da Vinci
The solution is a placenta – a vast network of intertwined capillaries from both mother and child. To keep out the mother’s immune system, the cells lining the fetal side of the placenta merge into one giant cell, leaving no gaps for white blood cells to squeeze through. This single cell layer is called a syncytiotropoblast, created by the production of syncytin [2].
But syncytin is an odd gene. It’s produced nowhere else in the body, only a particular type of cell in the placenta and then never again after birth. And it’s related to a protein found in retroviruses – a protein that helps viruses invade our cells [3].
We’ve discussed retroviruses before. A retrovirus inserts its viral RNA into the host cell’s genome using an enzyme called reverse transcriptase [4]. The host cell then reads these genes like an instruction manual to build more viruses. A gene similar to syncytin allows the virus to incorporate it’s membrane with that of the cell – sort of like a smaller soap bubble merging with a larger one.
Millions of years ago, an early mammal was infected with a virus that had this syncytin gene. After the infection had subsided, the syncytin gene was left in the mammals genome and it somehow found a way to put it to work, merging one cell with another cell to create a better barrier for the placenta [5].
Retroviral infection with syncytin. 1) Virus invades the cell using syncytin to merge with the cell membrane. 2) Reverse transcriptase converts viral RNA into DNA. 3) The syncytin gene integrates into the cells genome. 4) The cell copies the syncytin gene. 5) The cell produces its own syncytin and uses it to merge with surrounding cells to form a syncytiotrophoblast.
According to DNA analysis, this adoption of viral DNA happened more than once. The human syncytin gene is similar to that of other primates, but completely unique from the syncytin genes found cats, mice, and rabbits. So far, scientists have found six different versions of the syncytin gene in related species of placentals, suggesting multiple ‘infection’ events and a huge selective advantage to retaining this gene [6]. So even though the placenta developed first without viral DNA, the addition of syncytin was so beneficial that everyone starting doing it.
An estimated 8 percent of our genome came from viruses – the spoils of war after an infection. Most of our viral DNA is in pieces and sits dormant, but a few are functional and even essential to our survival [7]. Odd to think that pregnancy functions thanks to an ancient viral infection. Definitely a happy accident.
References
[1] “Placenta ‘Fools Body’s Defences’“. BBC. 10 November 2007.
[2] Musicki B, Pepe G, Albrecht E. (1997). “Functional differentiation of placental syncytiotrophoblasts during baboon pregnancy: developmental expression of chorionic somatomammotropin messenger ribonucleic acid and protein levels.” J Clin Endocrinol Metab 82 (12): 4105–10, PMID 9398722
[3] “Virus Gene Syncytin Insinuated Itself in Mammalian DNA Millions of Years Ago“. SciTechDaily.com. 18 February 2012.
[4] Kurth, Reinhard; Bannert, Norbert, eds. (2010). Retroviruses: Molecular Biology, Genomics and Pathogenesis. Horizon Scientific. ISBN 978-1-904455-55-4.
[5] “The Syncytin Gene: Viruses Responsible for Human Life“. IScienceMag. 10 June 2015
[6] “Mammals Made by Viruses“. Discover Magazine. 14 February 2012.
[7] “Our Inner Viruses: Forty Million Years in the Making“. National Geographic. 1 February 2015.
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