Muscle Performance

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Introduction

Athletic performance can be influenced by a number of factors, some of which are genetic. Genes determine between 20-80% of the variation in traits like oxygen intake, cardiac performance, and muscle fiber composition. To date, more than 150 genes have been linked to different aspects of physical performance. One of the clearest associations is seen with a gene called ACTN3 that is normally turned on in a type of muscle fiber used for power-based sports. A single SNP can turn this gene off. While this genetic change does not cause any health effects, it may contribute to whether you are a sprinter or a marathoner.

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Results

CC Two working copies of alpha-actinin-3 in fast-twitch muscle fiber. Many world-class sprinters and some endurance athletes have this genotype.

CT One working copy of alpha-actinin-3 in fast-twitch muscle fiber. Many world-class sprinters and some endurance athletes have this genotype.

TT No working copies of alpha-actinin-3 in fast-twitch muscle fiber. Few world-class sprinters have this genotype, but many world-class endurance athletes do.

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Heritability and Environmental Factors

Athletic performance has different estimates of heritability, depending on what aspect one examines. For example, differences in the relative proportion of fast-twitch and slow-twitch muscle fiber are thought to have a heritability of about 45%. Although it is not yet clear whether ACTN3 genotype affects this proportion, it has been shown that the SNP in ACTN3 that we report accounts for about 2.3% of the variation in sprinting performance. However, at the molecular level, whether you have 0, 1, or 2 working copies of alpha-actinin-3 is highly heritable. Lastly, muscle fiber only contributes a small part to your overall athletic performance. Other physical characteristics, such as lung capacity, and behaviors, such as regular exercise, also make important contributions to your prowess in sports.

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How the Biology Works

Go Time

When it's time to move, whether it's a leisurely walk on a sunny afternoon or an all-out sprint to catch the bus, your desire to get from Point A to Point B is sent from your brain to your muscles. Your muscles contract, the contractions move your bones, and away you go!

Each muscle in your body is composed of many separate muscle fibers. The muscle fibers come in two main varieties. So-called "fast-twitch" fibers are specialized for actions that require a powerful burst of force, like sprinting or lifting weights. "Slow-twitch" fibers, on the other hand, are good for activities requiring endurance such as long distance running or cycling.

Both types of muscle fibers need energy to contract. This energy comes from a molecule called ATP that is made within cells. Slow-twitch fibers make ATP using sugar and oxygen brought to them by the bloodstream when your heart starts pumping and your breathing increases. Fast-twitch muscle fibers make ATP by breaking down complex sugars that have been stored up in the muscle cells. They don't need oxygen for this process, which is good since it can take a minute or two for your heart and lungs to really get going.

Most of us have about a 50-50 split when it comes to fast- and slow-twitch muscle fibers. This may reflect the fact that during evolution our ancestors sometimes needed the ability to move quickly and powerfully (to escape a predator), but at other times needed to go strong for the long haul (perhaps while traveling great distances).

As always, there are exceptions to the rule. In studies of elite athletes, researchers have found that many top endurance athletes have a higher proportion of slow-twitch muscle fibers (sometimes up to 80%), while the best power athletes often have a higher proportion of fast-twitch muscle fibers (again, up to 80%).

Numbers Aren't Everything

Even though some super athletes may be endowed with exceptional muscle fiber profiles, there are other factors such as the strength of your heart and your lung capacity that contribute to your sports prowess.

A gene called ACTN3 also has an effect on athletic abilities. This gene makes a protein called alpha-actinin-3 in fast-twitch muscle fibers. More than a billion people world-wide have two copies of a SNP in ACTN3 that causes them to completely lack alpha-actinin-3 in their muscles. Scientists have shown,in both elite athletes and everday people, that people who lack alpha-actinin-3 in their muscles are at a disadvantage when it comes to power sports.

It's good to keep in mind that the size of your muscles matters too. You may not be able to change the number of muscle fibers you have or the proteins they contain, but you can make them bigger—so it’s time to hit the gym!

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Major Discoveries

1873

French anatomist Louis Antoine Ranvier observes two types of muscle fibers in various animals. One type appears dark red and contracts slowly when stimulated, while the other type appears white and contracts quickly.

1926

Dorothy Moyle Needham discovers that the red color typical of slow-twitch muscle fibers is due to a higher concentration of myoglobin, a protein that increases the amount of oxygen available to the muscle.

1976

Studies show that successful endurance athletes have a relatively higher proportion of slow-twitch to fast-twitch muscle fibers in their trained muscles. On the other hand, sprinters have muscles that are composed predominantly of fast-twitch fibers.

1978

Scientists find that instead of depending on muscle fiber proportions, endurance performance is actually more related to athletes' maximal oxygen uptake.

1992

The genes for alpha-actinin-2 and -3 are discovered. Alpha-actinin-2 is found to be turned on in both cardiac and skeletal muscle fibers, but alpha-actinin-3 is only turned on in skeletal muscle.

1999

Studies show that a common genetic variation can prevent the gene for alpha-actinin-3 from making its protein. It is estimated that about 18% of the world's population has two copies of this version of the gene, meaning that they completely lack the protein encoded by alpha-actinin-3 in their muscles. It is also shown that alpha-actinin-3 deficiency is not associated with any type of disease.

2003-2007

A study of elite athletes in Australia suggests that people who have at least one copy of the functional version of the alpha-actinin-3 gene have an advantage for power and sprint sports activities (which depend on fast-twitch muscle fibers). Studies of Finnish (2005), Greek (2007), and Spanish (2007) athletes confirm these results, as does a study of non-athlete Greek adolescents (2007). Results of the Australian study also suggest that those people who carry two copies of the non-functional version of alpha-actinin-3 have an advantage in endurance sports (which are dependent on slow-twitch muscle fibers).

November 2006

A study of professional endurance cyclists in Spain shows that carrying two copies of the version of the alpha-actinin-3 gene that does not make protein does not appear to confer an advantage in endurance sports, as suggested by earlier studies. This result is confirmed in an October 2007 study of Ironman triathletes.

September 2007

Demonstrating that genetics are not destiny, a two-time Olympian long jumper from Spain (who relies on his fast-twitch muscle fibers for his sport) is shown to carry two copies of the version of alpha-actinin-3 that does not make functional protein.

October 2007

Scientists working with knockout mice show that fast-twitch muscle fibers lacking alpha-actinin-3 (as is the case in people with two copies of the T version of the ACTN3 SNP) have altered metabolism, using more oxygen.

November 2007

A group in Belgium publishes evidence that people who lack alpha-actinin-3 protein in their muscles have more of one kind of fast-twitch muscle fiber. This type of fiber uses greater levels of oxygen, compared to the type of fiber found in people whose muscles make alpha-actinin-3.

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References

Costill et al. (1976) . “Skeletal muscle enzymes and fiber composition in male and female track athletes.” J Appl Physiol 40(2):149-54.

MacArthur and North (2004) . “A gene for speed? The evolution and function of alpha-actinin-3.” Bioessays 26(7):786-95.

Zierath and Hawley (2004) . “Skeletal muscle fiber type: influence on contractile and metabolic properties.” PLoS Biol 2(10):e348.

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Related Links

How Exercise Works at HowStuffWorks

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Gene/SNP Summaries

Gene or region: ACTN3

SNP: rs1815739

This gene produces a protein called alpha-actinin-3 that is only turned on in fast-twitch muscle fibers (the kind used for power events like sprinting or weightlifting). The protein forms part of the contractile machinery in muscle cells, where it is thought to play both structural and signalling roles.

The T version of the SNP in this gene prevents the full protein from being made. People with two copies of the T version thus have a total lack of alpha-actinin-3 in their fast-twitch muscle fibers. Those with the CT genotype have one functional copy of the gene and can still make the protein.

Surprisingly, a complete lack of the alpha-actinin-3 protein doesn't seem to cause any type of disease. This is probably because another closely related protein can step in for alpha-actinin-3 in people without a functional copy. The substitute protein likely does not perform its job as well as alpha-actinin-3, resulting in worse performance in power exercises.

Despite lack of a disease outcome, researchers wondered if the absence of alpha-actinin-3 might have an effect on athletic performance. Studies of elite athletes in Australia and Finland showed that power athletes—those whose performance depends on fast-twitch muscle fibers—were much more likely to have at least one working copy of the gene than non-athletes. In one study of Olympic power athletes (i.e., the best of the best), all had at least one working copy. Similar results were found in a study of Spanish professional soccer players.

But does alpha-actinin-3 make a difference for non-athletes? In fact, it does.

One study looked at a group of Greek teenagers who had been tested for a variety of fitness measures related to power and endurance sports. In this group, ACTN3 genotype had no effect on the girls, but boys with the TT genotype were significantly slower in a 40 m sprint. Interestingly, running was the only power event that the different versions of ACTN3 seemed to affect. For activities like throwing a basketball or jumping into the air, performance was unaffected by genotype.

Another study looked at arm strength in a group of people before and after 12 weeks of strength training. ACTN3 genotype appeared to have no effect in men, but women with the TT genotype had lower strength at the beginning of the study. After the training program women with the TT genotype—those without a working copy of alpha-actinin-3—had made greater gains than the women with at least one functioning copy. This was true in both European and Asian women.

Scientists aren't really sure why having alpha-actinin-3 would improve power performance. One theory is that the protein prevents damage in fast-twitch muscle fibers. The group who conducted the study of Greek teenagers thinks this explains why only running and not other power activities were affected by a lack of alpha-actinin-3. Running involves repeated use of the muscles, while jumping only uses muscles once: damage is not an issue.

The scientists who saw that women with the TT genotype were able to build up more strength than other women also think alpha-actinin-3 protects muscle fibers from damage. Muscle damage is what stimulates muscles to adapt and become stronger. Those with the TT genotype lack the protection against damage that alpha-actinin-3 normally provides, thus allowing a greater gain in strength.

Alpha-actinin-3 may also affect athletic performance by virtue of its effects on oxygen usage in muscle. Two studies (one in mice and one in humans) have shown that fast-twtich muscle fibers that lack functional copies of ACTN3 use more oxygen than those with at least one working copy. This type of metabolism might slow them down. Mice studies have also shown that these altered fibers are weaker and smaller than fibers containing alpha-actinin-3, but they are more efficient an resistant to fatigue—a situation that is better suited to endurance sports than sprinting.

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