By: Kyle Nickel
Biochemistry and Molecular Biology Graduate Student
How Genetics Can Save Your Dinner Party
Imagine this scenario: two people have the exact same error (or mutation) in the exact same gene. However, one person shows devastating symptoms of a genetic disease while the other has mild or no symptoms at all. This situation is the reality for many genetic diseases [1]. The reason for this shocking difference can be due to something known as a suppressor. A suppressor is a gene somewhere else in your genome (the instructions in your cells) that offsets the effect of the original mutation. Figuring out how suppressors work can teach us about how genetic diseases occur. They could also lead to something even greater: a cure.
What is a gene anyways?
The genes in your body are the instructions to create the components that your cells need to survive, called proteins. These proteins can do a variety of tasks. They can bind with each other, turn each other on and off, and even break each other down into pieces. Proteins carry out most of the essential tasks in your cells, often working in cooperation with each other. The interactions between genes and the proteins they encode form the basis for all of biology. When genes have mutations, the corresponding proteins can fail to do their job. This can lead to all kinds of unpleasant outcomes. Suppressors can then save the day by compensating for this shortcoming.
How do suppressors suppress?
A good analogy for how suppressors work is home decoration. If your original mutation is a large red wine stain on your new white couch, the outcome is an obvious stain on your couch. However, a conveniently placed pillow covering the stain is a “suppressor”. This reduces the severity of the outcome, so that it appears as a normal-looking couch to anyone who comes to visit. The original mutation is still there, lurking under the decorative pillow. But the suppressor makes it so that to the outside perspective of your guests, your dinner party went off without a hitch. In other words, suppressors are other genes (or even a second mutation in the same gene) that can somehow compensate for the shortcomings of the initial mutation.
Suppressors can also tell us a whole lot about human biology. A gene that suppresses another gene means that they are interacting in some way. As any gossip-obsessed teenager at a middle-school dance understands, knowing who is interacting with who is critical information. Without genes interacting, key tasks like cells moving, dividing, and even using energy would all be impossible. When gene interactions are disrupted, things like cancer, birth defects, and genetic diseases can occur. Learning about these interactions has much to show us about how our cells work.
What can suppressors do for YOU?
So, what can suppressors teach us about how to treat, and maybe one day cure, genetic diseases? Let’s return to the initial scenario of the two people with the same mutation. Geneticists can try to figure out exactly which gene (or genes) is suppressing the disease-causing gene and how. Once that is known, the next step is to design a drug that mimics the suppressor. Someone with severe symptoms can then take this drug, hopefully returning them to a long, happy life of dinner parties and unstained couches.
Could it be that simple? Are genetic diseases soon to be a thing of the past? No, probably not. As with all things in biology, it is never that neat and tidy. While I have talked about suppressors, there is the other side of the coin, which are enhancers. These are variants in the genome that can increase the severity of the original mutation. Think of enhancers as your clumsy friend who accidentally spills tomato sauce right by the wine stain on your couch, making the situation that much worse. Our genes form complex networks of suppressors and enhancers, with different genes interacting, seemingly with the express purpose of making life hard for geneticists. Trying to pick apart why two people with the same mutation have different outcomes is far more complex than can be explained with home decoration. So, do we even stand a chance against enhancers and suppressors?
New techniques have resulted in these answers coming in faster and faster. The original Human Genome Project cost $2.7 billion to sequence a human genome for the first time [2]. Now, you can get your genome sequenced for less than $1000, giving you instant savings of about $2.7 billion. Not only is that a great deal, but it also makes life much easier for geneticists. Learning about how human genes work and interact is much easier now than it has ever been before. This opens all sorts of new possibilities for treating genetic diseases and understanding what makes us tick. All this progress has amazing potential for improving the lives of everyone. According to the wise words of neuroscientist David Eagleman, “Our reality depends on what our biology is up to.”
References
[1] Rahit, K. M. T. H., & Tarailo-Graovac, M. (2020). Genetic Modifiers and Rare Mendelian Disease. Genes, 11(3), 239. https://doi.org/10.3390/genes11030239
[2] Singh, S. (2018). The hundred-dollar genome: a health care cart before the genomic horse. CMAJ : Canadian Medical Association Journal, 190(16), E514. https://doi.org/10.1503/CMAJ.69259
Image by Arek Socha from Pixabay