Natural Athleticism: Slam Dunk or Foul?

By Rebecca Fleeman

March Madness, the annual American college basketball tournament of the top 68 Division 1 teams, and arguably the best form of entertainment all year, came to a close on Monday. Full of single-elimination games that have fans jumping out of their seats, the seven-round tournament is laden with legendary athletes who will become pro. Watching the games over the past few weeks, I began thinking about the athletic ability of these players. I grew up playing basketball and even played competitively in high school, but I never became a college player and definitely did not win an NCAA tournament. What separates my average ball skills with the athletes on our screens who can jump higher, dribble better, throw further, and sprint faster than me? The wide gap in athleticism is mainly due to hard work and practice time; however, are some differences between amateur athletes and professionals rooted in the genetic cards we were each dealt?

Are there certain genes that make you a better athlete?

Since the first sequencing of the human genome in 2003, the number of genome-wide association studies (GWAS) has skyrocketed. With the ability to now sequence each person’s genome in less than 30 hours, a number of studies have compared the genetic makeup of athletes across multiple sports, from endurance-trained marathon runners to explosive movement body builders. This new field, dubbed “sports genomics” aims to fully understand what contributes to the power, strength, coordination, flexibility, cardiovascular capacity, and mentality of top athletes1. In sports genomics studies, researchers look for single-nucleotide polymorphisms (SNPs) from whole-genome microarrays to find the differences between elite athletes and us benchwarmers (Figure 1). Essentially microarray sequencing experiments take a small amount of DNA from humans and determine the order of the four DNA bases that make up our DNA. Most of the sequences are similar between humans, so the single base changes, the SNPs, are what set people apart in the microarray. Researchers record all the SNPs and analyze whether any SNPs occur more frequently in athletes versus non-athletes.

Figure 1: To find genes associated with athletic performance, researchers use DNA from humans to find single nucleotide polymorphisms (SNPs) that are common within a group of athletes by whole-genome sequencing. Figure created by R. Fleeman in Biorender.

Importantly, complex traits, like athleticism, are polygenic, meaning multiple genes contribute to the trait. Things like skin color, hair color, and eye color are all polygenic traits, which is why everyone is so unique. Each SNP found, therefore, likely only contributes to a small percentage of athletic performance (0.1-1%)1 and this large amount of variability makes it extremely difficult to find candidates for “the athlete gene.” Indeed, finding a SNP does not mean the SNP is causative of the trait, merely that the SNP is associated with the trait and is likely to contribute to the trait since they were inherited together. To find the definitive cause of the trait, you need some fine mapping and additional experiments. So far, over 155 genes have been discovered to be associated with athletic performance1. Because different sports require extremely different traits (think about the athletic capabilities you would want to have as a Tour de France cyclist versus an NFL lineman), scientists have divided the SNPs into endurance SNPs and power/strength SNPs.

The gene for speed

The ACTN3 gene SNP was one of the first SNPs discovered for athletic power and is one of the most well studied1,2. ACTN3 encodes a protein called α-actinin-3 that is expressed exclusively in type-II muscle fibers, and is commonly known as “the gene for speed3.” Muscles are made up of individual muscle fibers that come in two varieties, type-I and II, also known as slow-twitch and fast-twitch, respectively. Within these fast-twitch fibers, ACTN3 aids in the explosive contractile function of the muscle. In the general population, 25% of Asians, 18% of Caucasians, and 3% of African Americans have an ACTN3 SNP which results in a premature stop codon, leading to no ACTN3 expression3. The absence of ACTN3 expression in the type-II (fast-twitch) muscles is deleterious for those wanting to be power athletes because the truncated ACTN3 cannot bind actin in the muscle fiber, reducing muscle strength potential4 and altering muscle metabolism5 (Figure 2). Thus, many power athletes do not have the ACTN3 SNP, whereas the average pick-up game sport player has a 3-25% chance of having the ACTN3 SNP3. Interestingly, ACTN3 has also been associated with decreased muscle damage and decreased incidence of sports injury2,3.

Figure 2: ACTN3 within the type-II muscle fibers can help increase strength in athletes. Figure created by R. Fleeman in Biorender.

Inheritance of height and weight

Height and weight are two extremely important variables when it comes to sports6, and are also polygenic traits. About 80% of your height is determined by the genes you inherit, while the other 20% is environmental impact (energy consumption, maternal smoking, undernutrition, etc.)7,8. One important gene for height determination is the HMGA2 gene which encodes a protein called the high mobility group protein that binds to DNA and may act as a transcription regulating factor7. Lifestyle choices and environment play a larger role in the determination of weight than they do height, but your weight is also partially determined by genetics9. There is no definitive answer for how much of your weight is determined by genetics, but many twin studies have attempted to better understand the impact of genetics versus environment on weight9. Additionally, GWAS have found hundreds of genes that contribute to weight and thus it is hard to pinpoint single genes for predicting weight.

Overall, it is difficult to boil down what exactly determines athletic ability. Genes including ACTN3 and HMGA2 contribute to athleticism, but so do hundreds of other genes. As genome sequencing becomes more readily available to the general public, I wonder how many of us will have our genomes sequenced in our lifetime. It is interesting to speculate about whether knowing your genetic makeup early on could help you choose which sport to pursue to increase your likelihood of success. Importantly, your genes and practice time are not the only contributing factors to athletic performance. In addition to genetics and training, mental acuity and grit are two other areas contributing to the success of athletes. These aspects of athleticism are garnering greater interest in the field of sport research to fully understand their contribution10.

Regardless of the impact of genetics, training, and other environmental factors, the college basketball players this year did not disappoint, with many killer dunks and several buzzer beater three-point shots. My countdown to March Madness 2022 is on though, and when I compare myself with the athletes on the court, I plan to dazzle my fellow arm-chair experts with some fun facts on sports genomics. Now if only I could obtain genome sequencing data on the teams, then maybe my bracket picks would be a little more profitable.

1.        Ahmetov, I. I., Egorova, E. S., Gabdrakhmanova, L. J. & Fedotovskaya, O. N. Genes and Athletic Performance: An Update. in Medicine and Sport Science 61, 41–54 (S. Karger AG, 2016).

2.        Pickering, C. et al. A Genome-Wide Association Study of Sprint Performance in Elite Youth Football Players. J. strength Cond. Res. 33, 2344–2351 (2019).

3.        Pickering, C. & Kiely, J. ACTN3: More than Just a Gene for Speed. Front. Physiol. 8, 1080 (2017).

4.        Clarkson, P. M. et al. ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J. Appl. Physiol. 99, 154–163 (2005).

5.        MacArthur, D. G. et al. Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat. Genet. 39, 1261–1265 (2007).

6.        Pickering, C., Kiely, J., Grgic, J., Lucia, A. & Del Coso, J. Can genetic testing identify talent for sport? Genes 10, (2019).

7.        Weedon, M. N. et al. A common variant of HMGA2 is associated with adult and childhood height in the general population. Nat. Genet. 39, 1245–1250 (2007).

8.        Silventoinen, K., Kaprio, J., Lahelma, E. & Koskenvuo, M. Relative effect of genetic and environmental factors on body height: Differences across birth cohorts among finnish men and women. Am. J. Public Health 90, 627–630 (2000).

9.        Elks, C. E. et al. Variability in the Heritability of Body Mass Index: A Systematic Review and Meta-Regression. Front. Endocrinol. (Lausanne). 3, 29 (2012).

10.      DeBeliso, M. & Cazayoux, M. Effect of grit on performance in Crossfit in advanced and novice athletes. Turkish J. Kinesiol. (2019). doi:10.31459/turkjkin.517615

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