Overview: Edit

Athletic and muscular performance is a trait that is widely varied amongst a population because of the wealth of environmental and genetic influences that can help determine someones performance. Collectively there have been more than 150 genes found to be directly related to aspects of athletic performance including cardiac output, oxygenation, and muscle fiber composition. 23andMe bases their measurement of muscular performance on the activation of a gene ACTN3. When a person expresses two copies of the T allele, a mutation of the gene located at SNP rs1815739, the gene fails to make a protein, alpha-actinin-3, slightly inhibiting the performance of fast-twitch muscle fibers. (2;1)

History: Edit

Greek 40m vtimes

Normal plot of the 40m sprint times of 17 and 18-year-old males. The subjects were separated based on genotype (CC, CT, TT) and higher centrile values indicate a quicker time.

The genes for alpha-actinin-2 and alpha-actinin-3 were discovered in 1992, and while alpha-actinin-2 is active in skeletal and cardiac muscle, alpha-actinin-3 is only present in skeletal muscle. In 1999 it was showed that genetic variation in the gene expression (TT) inhibits ACTN3 from making its protein, and it was determined that about 18% of the general population expressed this variation. This is also when it was determined that there is no disease state associated with the mutation. Multiple studies from 2003, 2005, and 2007 suggest that those athletes who have at least 1 functional copy of ACTN3 have an advantage in power/sprint based activities. One compelling Greek study from 2007 was performed on adolescent non-athletes, and it was revealed that there is a significant relationship between ACTN3 polymorphism and 40m sprint time of males, a notable 2.3% variance. However, the variance in the female group was negligible. Then in late 2007 it was discovered that humans without the alpha-actinin-3 protein have more of one kind of fast-twitch fiber that utilizes more oxygen than the fibers of someone who has the protein. That is to say the lack of the protein creates an imbalance in metabolism that is corrected by utilizing another structural protein that happens to have a higher level of oxygenation than alpha-actinin-3. (4; 3

Function of ACTN3 in Phenotype Edit

ACTN3 is a gene located on the 11th chromosome and produces a protein called alpha-actinin-3 which is a part of the contraction mechanism is fast-twitch muscles. The protein acts as an anchor in the crosslinking of myofibrillar actin filaments specifically in the sacromere portion of smooth muscle, and has a function in signaling that is not empirically determined. The T version of the SNP, rs1815739, prevents the protein from being made, and people with the TT genotype express none of the protein, leading to a decreased efficiency of the fast-twitch muscles and association of those people with a more endurance based form of muscle performance. However there is no phenotypical variation in performance between those who express only one copy of the gene (CT) and those who express both copies (CC). The definitive reason for the variation in performance is unknown but there have been two studies, one in mice one in humans, that revealed the muscle fibers where the protein is not expressed utilized more oxygen that normally, likely causing the physical variations. Although a recent mice study did reveal that these fibers that lack alpha-actinin-3 are more resistant to fatigue which further perpetuates the theory that the activation of this gene determines an affinity for either sprint or endurance based muscular performance. (1;2;3

John Burke's Genomic Model Edit


Taken from John Burke's 23andMe page, this image displays that John is a heterozygote in regards to the ACTN3 gene.

John Burke is a heterozygote, his genotype is CT, which means that he has one copy of the ACTN3 gene that is encoding for the alpha-actinin-3, and one copy of the mutated gene that is not encoding for protein proliferation. However there is no functional defect to having one dysfunctional gene, and all studies show that his muscle performance is homologous to those homozygotes expressing the CC phenotype. 23andMe indicates that John Burke is a likely sprinter, but its important to note that the function of muscle fibers is only a small part of overall physical performance. The key to being a sprinter or endurance athlete is training, but access to this knowledge can easily allow someone to narrow their focuses into a form of exercise that they genetically have a higher affinity for. (2) 

References Edit