(Cover Illustration by Julia Dingman)
Inside the DNA of Elite Athletes
To uncover what makes athletes perform at a superhuman level, analysts often examine diet, training regimens, and discipline. However, underlying factors may play an even greater role in dictating elite performance standards. Research shows that genes, segments of DNA that carry the instructions for building and maintaining the body, play a major role in shaping athleticism. One gene in particular, ACTN3, is nicknamed the “speed gene” for its critical role in influencing explosive power and speed in athletes.
The ACTN3 gene provides instructions for making α-actinin‑3, a protein expressed exclusively in type-II muscle fibers. These muscle fibers are the fast-twitch units that generate high-force movements and are commonly used in events such as sprinting, weightlifting, and jumping. A common genetic variation in ACTN3, R577X (rs1815739), changes muscle performance, influencing whether an individual is gifted with the natural ability for speed, endurance, or strength. Each possible genotype resulting from the variation can have both positive and negative implications on the athletic capabilities of an individual.
The Science Behind the Gene
The R577X variation occurs when a single DNA base changes from C to T. DNA consists of 4 bases: adenine (A), thymine (T), cytosine (C), and guanine (G). To form the genetic code, these bases pair specifically, with A pairing with T and C pairing with G. When this substitution occurs, the instructions for making the α-actinin‑3 protein alters, replacing an arginine amino acid (R) with a premature stop codon (X), disrupting normal protein production. The mutation results in three possible genotypes, each of which reflects different levels of performance in humans.
Individuals with an RR genotype produce normal levels of α-actinin‑3, which is associated with better sprinting ability, greater power, and enhanced explosive strength. Those with an RX genotype produce a partial amount of α-actinin‑3, resulting in a balanced combination of power and endurance. In contrast, individuals with the XX genotype do not produce α-actinin‑3, which is linked to better endurance but reduced explosive power.
The α-actinin‑3 protein localizes to the Z-disk in type II fast-twitch muscle fibers, helping collect actin filaments during high-force and speed contractions. Loss of α-actinin‑3 subtly shifts twitch fiber properties towards slower, more oxidative behavior, helping improve fatigue resistance, but consequently reducing peak power.
Individuals with the RR genotype excel in sports that require great speed or immense strength. Examples of such sports include the 100-meter dash and strongman competitions. Individuals with the XX genotype outperform others in activities that require stamina and aerobic endurance. Examples of such activities include triathlons, which contain long-distance running, biking, and swimming.
Methods Corner: Insights from Multiple Athletic Studies
How Performance is Measured
Research on ACTN3 gathers evidence from several different methods: genotyping confirms R577X status in individuals; field tests (100-yard dash, jump height) and lab measurements (1 rep-max, Wingate power) determine output; aerobic profiling (VO2 max, lactate threshold) measures endurance; and more specialized muscle biopsies uncover protein expression and twitch-fiber types. A combination of the methods and their results strengthens conclusions about the real-world effects of ACTN3 gene mutations and benefits (and tradeoffs) that come with each one.
ACTN3 and Elite Power Athletes
According to a 2024 meta-analysis of over 14,500 participants, the RR genotype and R-allele—key markers for explosive strength—were significantly more common in elite power athletes than in endurance athletes or non athletes (Ouali et al., 2024). The presence of α-actinin‑3 plays an important role in stabilizing fast-twitch muscle fibers, allowing them to generate greater force while also recovering the muscles more efficiently in post high-intensity workouts.
Effect sizes vary by training regimens, sport demands (pure endurance vs. strength-power blends), and genetic characteristics. These three moderators explain why elite athletes are present in every genotypic combination, even if R-allele carriers are over-represented in power cohorts.
Evidence from Knockout Mice Studies
To better understand α-actinin‑3’s role, scientists studied “knockout mice” (KO) – mice genetically engineered to lack the ACTN3 gene – which mimic the XX genotype in humans. These mice exhibited decreased muscle force and reduced lean mass. They also developed smaller type II fast-twitch fibers and showed a metabolic shift toward oxidative, endurance-based pathways.
Additionally, the KO displayed signs of accelerated muscle degeneration with aging. These findings suggest that α-actinin‑3 is key for maintaining strong muscle structure, fast-twitch fibers, and explosive power movements. The metabolic shift in the mice – a change in how muscles produce energy – towards oxidative metabolism is similar to what is observed in humans lacking α-actinin‑3. This provides strong biological evidence that the RR genotype contributes to power-based performance in athletes.
The study reports that KO mice exhibit faster muscle degeneration as they grow older. In the prime stages of an athlete’s life, the XX genotype is associated with better endurance performance and aerobic efficiency due to a greater reliance on oxidative energy pathways. However, as the athletes grow older, their muscles begin to collapse and tire out, resulting in a progressive loss of strength and power. Thus, while the XX genotype may offer advantages to the youth, it also entails a long-term trade-off characterized by vulnerability to muscle degeneration.
Conclusion
The ACTN3 “speed gene” plays a crucial role in determining muscle composition, athletic levels, and long-term performance metrics. ACTN3 gene polymorphism, the natural variation in the gene’s expression and sequence, influences whether an individual is predisposed to possess a speciality in power-based sports, endurance-focused activities, or both. A simple change in the genotype (RR, RX, XX) can alter whether an individual can bench 600 pounds like Larry Wheels or swim 10,000 meters like Michael Phelps.
ACTN3 is a clear indication of how genetics influences human performance and athletic specialization. While training, diet, and consistency remain essential in forming a high-scale athlete, understanding genetic factors like ACTN3 provides deeper insight into why certain athletes dominate in their field of sports. In fact, further research on the levels of α-actinin‑3 production in individuals can bring a whole new perspective to the sports world, specifically targeting young athletes to specialize in their “field of expertise” from an early age. This, in turn, can shift the levels of performance in high-level athletics, utilizing genetics to create a more competitive and action-packed atmosphere.
Sources
https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2017.01080/full
https://sportsmedicine-open.springeropen.com/articles/10.1186/s40798-024-00711-x
https://academic.oup.com/hmg/article/17/8/1076/650247
https://pubmed.ncbi.nlm.nih.gov/32668587/
https://europepmc.org/article/med/17211191
https://pmc.ncbi.nlm.nih.gov/articles/PMC9219180/