AN INTRODUCTION TO THE ATHLETIC GENE

           The name of the recently proclaimed “athletic gene” is ACTN3. This gene, located at 11q13-q14, is responsible for the production of alpha actinin-3 (OMIM, 2004). Actinin-3 is found in fast-twitch (type 2) muscles and is believed to allow muscles the ability to generate a greater amount of force at higher velocities of movement. In words that even the most unintelligent sports fan could understand: this gene allows you to run faster, jump higher, and hit harder. Actinin-3 is a part of a family of actin-binding proteins and is related to dystrophin. There are two different genes located in the human body that are able to produce actinin. ACTN3 is one and the other is ACTN2. Unlike ACTN3, the presence of ACTN2 is found universally in all skeletal muscle, not just type 2. In all the research surrounding ACTN3 a strong connection could not be made to show that any dependency existed between the functions of ACTN3 and ACTN2. The most notable evidence being that ACTN2 expression does not completely overlap that of ACTN3 (Yang et al, 2003).
        The production of ACTN3 is the result of an individual possessing at least one copy of the R577R allele. The alternate allele to R577R is R577X, which harbors a premature stop codon, preventing the formation of actinin-3. The difference in the two alleles is that in R577X a TER amino acid has replaced the original ARG found on R577R (OMIM, 2004). Although a considerable amount of the population is homozygous for this null mutation there is not any sort of disease phenotype associated with this deficiency, proving that while ACTN3 would be desired by a large portion of the population it is not a gene essential for life. An interesting fact about ACTN3 is that the percentage of individuals who are homozygous for the R577X allele varies for people from different nations. For example, 25% of individuals from Asian populations do not possess a copy of the actinin-3 producing gene, for European populations 18% lack a copy, but for African Bantu populations only <1% of the individuals lack a copy of ACTN3 (Yang et al, 2003).

POPULAR PRESS: Gene Linked to Athletic Performance (see the article at www.discoveryhealth.co.uk)

        This article posted on the Discovery Health website summarizes an Australian research team’s findings that were published in the American Journal of Human Genetics. This article briefly explains that the research team investigated the connection between ACTN3 and athletic ability by taking the genotypes of over 300 athletes and comparing them with the genotypes of a large group of controls, and goes on to discuss the results that the research team obtained. The research team found a higher prevalence of the R577R allele in elite sprinters compared to the control, and that endurance athletes had the same prevalence for the R577R allele as the individuals who served as the controls. Following the discussion of R577R allele rates the article highlights the low number of elite sprinters with the R577X allele compared to those individuals in the control, information that could have been easily deduced by the high percentage of R577R allele for sprinters. The article concludes by mentioning that ACTN3 is in fact the second gene that has been linked to athletic performance. The first gene linked to athletic performance, the ACE encoding gene, was discovered at the University of London and is shown to influence how muscles utilize oxygen and the rate at which they grow.
        Although the article does not go into a large amount of detail it does provide a good deal of information to “the reasonable person” without any statements that could be perceived to offer false hope or make the discovery seem more grandiose than it actually is. In fact, the article concludes by mentioning that this discovery concerns only one of many factors that play a role in a person’s level of athletic ability and that ACTN3 is not the end-all deciding factor as to whether or not an individual is athletic.
       

SCIENTIFIC ARTICLE: ACTN3 Genotype Is Associated with Human Elite Athletic Performance (see the article from the American Journal of Human Genetics)

        This article, which served as the foundation for the popular press publication, is from the American Journal of Human Genetics. Like the popular press publication, the purpose of this article was to describe the study, results and significance of the findings made by the Australian research team that worked to develop a greater understanding of the connection between ACTN3 and certain athletic abilities.
        The evidence used in support of proclaiming ACTN3 as the “athletic gene” was gathered by an Australian research team from the Institute of Nueromolecular Research at the Children’s Hospital in Westmead, Sydney. To determine the effects of ACTN3 the team genotyped 436 unrelated white controls utilizing three different sources; blood donors, healthy children who had participated in another survey, and healthy adults who participated in a talent survey through one of the institutions involved in the research. These controls were held up against the genotypes of 429 “elite” white athletes from 14 different sports. The “elite” tag was awarded to athletes who had represented Australia in their respective sport at the international level, for example at the Olympics. The results from the study initially showed no significant differences in the allele frequency of the control and elite athlete group, but once the athletes were divided into two groups, those who played sports that required fast bursts of power and those who played sports that required a high level of endurance, the research team noticed that a new trend had taken shape.
        As mentioned under the discussion of the popular press article, sprinters and other athletes who played sports that required fast bursts of power had a higher frequency of the R577R allele compared with the control. What was somewhat surprising was that the allele frequencies for the endurance athletes were nearly identical to that of the control group. It turns out that when the allele frequencies for all the athletes were pooled as one group their differences cancelled each other out enough that the allele frequencies of the athletes was not all that different from the allele frequencies of the control.
 
 

                                                           Group (n)           No. (%) with Genotype      Allele Frequency (%)
                                                                                          RR          RX         XX                 R       X
                                                          Control (436)       130 (30)   226 (52)   80 (18)            56      44
                                                           Sprint (107)          53 (50)    48 (45)      6 (6)              72      28
                                                        Endurance (194)      60 (31)    88 (45)    46 (24)            54      46

Table 1. The number and percentage of people in each group with the different genotypes along with the allele frequency for each group
 

        Another unexpected result was that female sprinters had a higher frequency of the R577R allele than the male sprinters. Not a single female sprinter was homozygous for the R577X allele. This finding is likely to be evidence that ACTN3 affects athletic performance differently for men and women. The research team hypothesized that in males the effects of actinin-3 were not as important because the androgen hormone response to training is likely to make a much larger contribution in males compared to females.
        This article also provides more information about the ACE encoding gene, which was also believed to be linked to increase athletic ability. ACE stands for angiotensin-converting enzyme and the gene that encodes for this enzyme exists as either one of two alleles, referred to as the I and D alleles. The I allele is associated with a decreased amount of ACE production and is found more often in endurance athletes. The D allele is associated with an increased amount of ACE production and is found more often in sprinters. As you will recall from the summary of the popular press article the ACE protein is believed to influence how muscles utilize oxygen and the rate at which they grow.
        In trying to determine how the presence of actinin-3 allowed muscles to contract with more force the Australian research team speculated that the actinin-3 protein might confer a greater capacity for the absorption or transmission of force at the Z-line, site where actin is anchored, during rapid muscle contraction. The basis fo their speculation comes from the fact that the Z-line is the structure made the most vulnerable to exercise-induced injury and that by being better adapted to handle large amounts of force the muscles could perform at a higher level with a decreased risk of possible injury.
 

CRITIQUE
        Now that The Human Genome has been mapped and with new genes being discovered for just about everything, the article on Discovery Health website could easily give the impression that the one deciding factor of athletic ability has been discovered. Was this article going to prove that all times my father told me that if I wanted to be good I had to keep practicing were in fact just his way of trying to avoid telling me that the reason I cannot dunk a basketball is because he gave me a set of “faulty” genes? Somewhat, but not completely. After reading the article I was still aware that all the practice in the world would never get me into the NBA but I understood what had been discovered and was aware that this discovery only explained a small part of the many attributes needed to excel in sports. The popular press article concluded by iterating that this gene does provide an increased ability to perform certain actions but it does not control all the intricate components that go along with the being a better athlete. While being homozygous for R577R will allow to run faster than if you were homozygous for R577X the gene will not have any effect on hand-eye coordination, awareness (“court vision”), as well as many other traits necessary to excel on the playing field, whatever that field may be. On the whole the popular press publication did a good job of explaining what was discovered and what the significance of the discovery was. You can find fault with a job well done.
 

CONCLUSIONS
        After learning all about the research that was done and the links that have been made between the ACTN3 gene and its elevated prevalence among Australia’s elite athletes you begin to wonder why it is not seen more consistently throughout the population. What advantage does R577X alleles have over the power producing R577R alleles? The Australian research team hypothesized that the advantage of the R577RR genotype is only necessary in extreme circumstances of athletic competition, beyond the range of the activities that fill the normal man’s life. Another possible reason that the ACTN3 gene has not been selected for is because each of the alleles conveys to its host a particular advantage. While the R577R allele does appear to enhance sprinting ability, the R577X allele enhances an individual’s performance in activities that require a high level of endurance. Since most people do not require only one of these abilities but rather a combination of the two, it would seem that humans would be selected to possess a copy of each allele (Yang et al, 2003). The majority of the controls were heterozygous. In the end, these are only speculations based off of the data that was collected. Perhaps when more “athletic genes” are discovered scientists will be better suited to piece together this fascinating puzzle.
 
 

REFERENCES

Discovery Health. 2003. Gene Linked to Athletic Performance. <http://www.discoveryhealth.co.uk/general/g_story.asp?storyid=117622&oldstoryid=115904&feature=>. Accessed 2004 Sept. 13.

[PDB] Protein Data Bank. 2004. 1G8X. <http://www.rcsb.org/pdb/cgi/explore.cgi?job=graphics&pdbId=1G8X&page=&pid=121095222568>. Accessed 2004 Sept. 14.

[OMIM] Online Mendelian Inheritance in Man. 2004. ACTN3. <http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=102574>. Accessed 2004 Sept. 14.

Yang et al. 2003. ACTN3 Genotype is Associated with Human Elite Athletic Performance. Am. J. Hum. Genet. 73: 627-631. <http://www.journals.uchicago.edu/AJHG/journal/issues/v73n3/34986/34986.text.html>. Accessed 2004 September 13.
 
 

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