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8/29/2018

Oh, Those Gene Names

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I published a post regarding the names taxonomists give to new organisms they discover and how these names can be flattering, witty, rude, insulting, or downright funny. As it turns out there is another crowd in the biological sciences that has been having a jolly good time naming things, and these are the scientists who study genes. And among these scientists, those who study fruit flies seems to have had the most fun.
 
Now why on earth would someone want to study flies? To begin with, flies share about 60% of their DNA sequence with us, so many fly genes have equivalent human genes. Furthermore, flies have very short life cycles (which allows the study of several generations in a short time), they are easy and cheap to work with, and not only can fly mutants be studied to find out which genes are responsible for any alterations, but also the technology has been developed to modify, delete, or insert genes, and observe how these modifications change the anatomy, physiology, or behavior of the flies. All this has made fruit flies tremendously important in the study of human genetics. More than 100,000 research articles have been written by scientists employing these organisms as a model system, and a total of 6 Nobel prizes have been awarded to scientists who have used these insects to make key advances in several fields of science.
 
So, not surprisingly, the fly researchers have discovered and named quite a few genes. But what do you name a gene when you discover it? More often than not, fruit fly scientists have selected gene names based on whatever the particular condition that the fly experienced upon mutation of the gene reminded them of. Let’s take a look at a few.
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There is a gene that when mutated in fruit flies leads to problems in the development of external genitalia in the male and female. What possible name would you have given this gene? Fruit fly scientists christened it the Ken and Barbie gene after the anatomically imprecise plastic dolls.
 
There is a series of genes involved in the synthesis of steroid hormones in fruit flies. Mutations in these genes cause the fly embryos to develop scary-looking malformations in their exoskeleton. The names of the genes are: disembodied, phantom, shade, shadow, shroud, spook, and spookier. They are collective known as the Halloween genes.
 
There are several genes that affect alcohol tolerance in fruit flies. One lab discovered a gene that when mutated made flies more resistant to alcohol (named Happyhour), a gene that when mutated made flies more sensitive to alcohol (named Cheapdate) and a gene which helps flies become tolerant to alcohol over time (named Hangover).
 
Fruit flies have 8 photoreceptors in their compound eyes. Scientists discovered a gene that when mutated results in flies that lack the seventh photoreceptor in their eyes. Thus the gene was named Sevenless. Other genes that interacted with Sevenless were named in serial horror movie fashion: Bride of Sevenless (also known as BOSS), Daughter of Sevenless, and Son of Sevenless.
 
My favorite fruit fly gene is one that when mutated doubles the fly’s lifespan. The gene was christened INDY, which is an acronym for “I’m Not Dead Yet”. This is in reference to the Bring Out Your Dead scene from the Monty Python and The Holy Grail movie.
 
And the examples go on and on. What would you call a fly gene that when mutated results in flies with no hearts? Scientists named it, Tinman, after the character in The Wizard of Oz who did not have a heart. What would you call a fly gene that when mutated causes neurological degeneration with the production of holes in the brain? Swiss Cheese! What would you call genes that control the death of cells in flies? Grim and Reaper!
 
But the name doesn’t have to be related to what a mutation does to the gene. For example, several fly genes code for proteins that are located in an area of the fly’s tissue cells called “the matrix”. Accordingly these genes were named Trynity, Nyobe, Morpheyus, Neyo (Neo), and Cypher after characters in the movie The Matrix.
 
Despite the role of fruit flies in gene research, new genes have also been identified and named in other living things. For example, in the plant Arabidopsis thaliana there are two genes called Clark Kent and Superman that when mutated result in a plant with a large number of male parts (stamens) on their flowers. Interestingly, there is another gene called Kryptonite that when mutated causes the plants to lose their male parts and become sterile. A gene in the zebrafish that when mutated makes the fish extremely sensitive to light (so much so that light kills them) was christened “Dracula”. A gene in sheep that when mutated causes the animals to develop very prominent rear ends was named “Callipyge” which translates from Greek as “beautiful buttocks”. One final example is a gene in mice that codes for an enzyme that transfers a molecule of the sugar fucose to a protein. It was found that when this gene is mutated it causes the females to reject the sexual advances of the males. The name of the gene is the fucose mutarose gene, but it is better known by its acronym FucM !
 
Of course, as long as gene naming remained confined to insects or animals, all was fun and games. Unfortunately gene naming hit a snag. This was due on the one hand to how successful scientists were in finding counterparts of the genes of fruit flies and other animals in humans, and on the other hand to the fact that some of these genes were found to be associated with diseases. 
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Consider for example the gene Hedgehog. When this gene is mutated in flies, it causes the fly embryos to be covered with tiny spikes. The counterpart of this gene in mammals including humans was christened Sonic Hedgehog after Sega’s video game character Sonic The Hedgehog. It turned out that a mutation in the human Sonic Hedgehog genes produces a disease called Holoprosencephaly which causes brain, skull, and facial defects. So visualize the following situation:
 
“I’m sorry, Mr. John and Jane Doe, your child was born with cranial and facial malformations, due to a mutation in Sonic Hedgehog. He may die from the disease, or if he survives, he may experience a certain degree of mental retardation or behavior problems and seizures. What is Sonic Hedgehog? Oh, it’s a gene named after a video game character. Ha, ha, ha, funny isn’t it?”
 
As Sonic Hedgehog and other genes became linked to deadly or life-altering human diseases, clinicians became uncomfortable with explaining the inside jokes behind these playful but sometimes rude or insensitive names to patients and their families. Because of this the Human Genome Organization Gene Nomenclature Committee consulted with many scientists and renamed several of the worst offenders. So now, for example, the committee recommends that Sonic Hedgehog be known by the acronym SHH.
 
From all the foregoing you may derive the impression that the scientists who name these genes are foolish, but nothing could be further from the truth. These funny names represent some much needed levity in what is very hard and at times very frustrating work, and these scientists have produced key advances that have increased our knowledge of how our body works and that have also saved lives. The first drug that fights cancer by targeting the Sonic Hedgehog signaling pathway in cells, Vismodegib, was approved by the FDA in 2012.
 
So next time you hear about the Moonwalker fly (a fly that walks backward when certain neurons are activated by genetic manipulations in a manner reminiscent of Michael Jackson’s famous dance move), or the Stargazer mouse (a mouse that rears its head upwards due to a mutation in a signaling gene), think about the many nights and weekends that the scientists that worked with these critters spent in the labs and give them a smile.

 
Image of a fruit fly by Sanjay Acharya, used here under an Attribution-ShareAlike 4.0 International (CC BY-SA 4.0). license. Image of Sonic the Hedgehog by Chris Dorward used here under an Attribution 2.0 Generic (CC BY 2.0) license.

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