Chicken-or-Egg Paradox Sheds Light on Genetic Variants
The dilemma of untangling cause and effect is perhaps best encapsulated by the chicken-or-egg paradox. It may provide cocktail party banter, but to an evolutionary biologist, it’s pretty simple: eggs are much older than chickens. At some point, an almost-complete chicken creature produced an egg from which a full-fledged chick pecked its way out.1
Genetic variation is at the heart of this yolky evolutionary tale—just like it’s at heart of genetic disease research.2
Evolution and genetic variation
When the physical characteristics and genetic makeup of species change over time, we call it evolution. But evolution as we know it depends upon the intrinsic genetic variation within a population.3 Genetic variation refers to the variable and permanent changes that occur within the DNA sequence coding for a gene. One or more nucleotides may encompass a genetic variant.4
Genetic variants generally arise in 1 of 3 ways: through heredity, non-heredity, or spontaneously in children. Heritable variants are passed from parent to child, are present for the affected person’s lifetime, and can be found in virtually every bodily cell.4
Non-heritable variants arise at some time in a person’s life—possibly as a result of an error during cell division, or from environmental or occupational exposure to factors like ultraviolet radiation. Non-inherited variants may be found in bodily cells other than sperm or eggs and are and often called somatic variants. But sometimes variants simply appear in children, without being in either parent—though in some cases the variant may also occur only in a parent’s sex cells (eggs or sperm).4
Forms of genetic variation
Genetic variants occur in many different forms. Some arise due to nucleotide substitutions, where base pairs are swapped. Others arise from the insertion or deletion of a nucleotide — or sometimes simultaneously in what’s referred to as an indel variant. When spans of 1 or more nucleotides are copied by mistake, it’s called a duplication variant, and when they are copied multiple times it is known as a repeat expansion. Sometimes multiple nucleotide sequences are even copied backward, in what is called an inversion variant. All of these variants can result in muddling coding instructions that produce proteins that do not work properly.5
When someone carries a genetic variant that is linked to a disease or health condition, the variant affects how their cells make proteins. Every cell in our bodies relies on the careful orchestration of proteins that must be in certain places at certain times to do certain things. When a variant alters the instructions for how to make a protein—maybe it makes too much, too little, or none at all—the cascading effects may interfere with normal development or produce a health condition or disease. Some variants can be severe enough to be incompatible with life, while others produce mild or severe disease.6
Classifying genetic variants and their role in disease
A small proportion of variants provide positive benefits and many have no impact on health or development at all. But some are associated with, or cause, disease. Researchers have a system for classifying variants to describe their role in disease. People who receive genetic testing, for example, may be told that a variant they carry is:7
- Pathogenic: there is lots of evidence it causes disease
- Likely pathogenic: the evidence is weaker, but it probably causes disease
- Variant of uncertain significance: there is not enough evidence for scientists to say what role it plays, the evidence neither confirms nor rejects that it causes disease
- Likely benign: the evidence shows the variant likely does not cause disease
- Benign: lots of evidence shows the variant does not cause disease
But genes are not destiny. Recent research shows there is actually a low risk, roughly 7%, of developing disease when someone carries a known pathogenic variant.8
Why disease-causing genetic variants persist
We tend to think of evolution as a self correcting process that finds and amplifies advantageous genetic variations. For example, some genetic variants may provide an advantage to survival that can be inherited.3 But then how to explain why deleterious, harmful, genetic variants persist in populations and produce disease and disability?9
This can happen for a couple of reasons. First, some genetic variants may not show up until later in someone’s life, after they’ve already passed on their genetic contribution to their children. Second, some people who carry a variant may not show signs or symptoms of the disease it is associated with and they may pass it on without ever knowing they have it. This is known as reduced penetrance. Third, there are also cases where having 1 copy of a variant provides an advantage, such as disease resistance, whereas having both copies produces disease.9
- Bittel J. Chicken and egg question goes back to ancient times, but there’s a simple answer. 3/24/2020. Washington Post. Available at https://www.washingtonpost.com/lifestyle/kidspost/chicken-and-egg-question-goes-back-to-ancient-times-but-theres-a-simple-answer/2020/03/24/7ece878a-60e0-11ea-9055-5fa12981bbbf_story.html. Accessed 4/6/2022.
- Fabry M. Now you know: Which came first, the chicken or the egg? 9/21/2016. Time. Available at https://time.com/4475048/which-came-first-chicken-egg/. Accessed 4/6/2022.
- What is Evolution? Your Genome. 2/17/2017. Available at https://www.yourgenome.org/facts/what-is-evolution. Accessed 4/6/2022.
- What is a gene variant and how do variants occur? MedlinePlus. 3/25/2021. Available at https://medlineplus.gov/genetics/understanding/mutationsanddisorders/genemutation/. Accessed 4/6/2022.
- What kind of gene variants are possible? Medline Plus. 11/4/2021. Available at https://medlineplus.gov/genetics/understanding/mutationsanddisorders/possiblemutations/. Accessed 4/6/2022.
- How can gene variants affect health and development? Medline Plus. 3/25/2021. Available at https://medlineplus.gov/genetics/understanding/mutationsanddisorders/mutationscausedisease/. Accessed 4/6/2022.
- Do all gene variants affect health and development? Medline Plus. 3/25/2021. Available at https://medlineplus.gov/genetics/understanding/mutationsanddisorders/neutralmutations/. Accessed 4/6/2022.
- Most pathogenic variants are associated with low risk of causing disease, study finds. Genetic Engineering and Biotechnology News. 1/26/2022. Available at https://www.genengnews.com/genetics/most-pathogenic-variants-are-associated-with-low-risk-of-causing-disease-study-finds/. Accessed 4/6/2022.
- How are gene variants involved in evolution? Medline Plus. 8/5/2021. Available at https://medlineplus.gov/genetics/understanding/mutationsanddisorders/evolution/. Accessed 4/6/2022.