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Essay: The makings of the perfect athlete

2005; Elsevier BV; Volume: 366; Linguagem: Inglês

10.1016/s0140-6736(05)67828-2

1474-547X

Yannis Pitsiladis, Robert A. Scott,

Genetic Associations and Epidemiology

Compared with primates, people have several anatomical and physiological facets that have evolved over time and that lend themselves to endurance running. Although these adaptations are common to all modern human beings, there are great differences in physical performance between populations. This fact raises the intriguing possibility that certain populations might have further adapted, predisposing them to higher levels of physical performance. The dominance of long-distance running events and sprint events by east African and west African athletes, respectively, is often described as an example of population specialisation, but the extent to which these successes are mediated by genetic variation is unknown.Within all populations, including seemingly specialised populations, there exists large interindividual variation in physical performance. Most people—whether from an urban city like Glasgow, UK, or from the town of Eldoret in rural Kenya, from where a disproportionately high number of Kenyan running legends originate—will recall from their youth some children who seemed to be naturally better at certain sporting events than others. Even at the elite level, only a relatively small number of athletes compared with the number in training will win an Olympic or World Championship medal during their career, though the training regimes of those who do and do not win might be similar, with some even sharing the same coach. There is good evidence that lends support to the theory that athletic capability is inborn, resulting in the disparity in physical performance noted, without excluding the importance of the environment in enhancing any favourable, or overcoming any unfavourable, genetic predisposition.National patterns of success in athletic competition are evident in the medal tally at major competitions. For example, athletes from Ethiopia and Kenya won nine of the 12 available medals for the 5000 m and 10 000 m at the 2003 World Championships in Paris. Furthermore, all male world record holders for athletic events, ranging from the 100 m to the marathon, are of black African ancestry (table). Athletes of west African ancestry hold records for the 100–400 m events, whereas those of east or north African ancestry hold records for the longer distances.TableMen's world running recordsDistanceAthleteTimeAncestry100 mAsafa Powell (JAM)9·77 sWest Africa110 m hurdlesColin Jackson (GBR)12·91 sWest Africa200 mMichael Johnson (USA)19·32 sWest Africa400 mMichael Johnson (USA)43·18 sWest Africa400 m hurdlesKevin Young (USA)46·78 sWest Africa800 mWilson Kipketer (KEN)1 min 41·11 sEast Africa1000 mNoah Ngeny (KEN)2 min 11·96 sEast Africa1500 mHicham El Guerrouj (MOR)3 min 26·00 sNorth AfricaMileHicham El Guerrouj (MOR)3 min 43·13 sNorth Africa3000 mDaniel Komen (KEN)7 min 20·67 sEast Africa5000 mKenenisa Bekele (ETH)12 min 37·35 sEast Africa10 000 mKenenisa Bekele (ETH)26 min 20·31 sEast AfricaMarathonPaul Tergat (KEN)2 h 4 min 55 sEast Africa Open table in a new tab Such statistics have led to the presumption that athletes of black skin colour are genetically endowed natural athletes. This notion is based on the preconception that every race, defined solely by skin colour, constitutes a genetically homogeneous group. This idea is contrary to the finding that there is more genetic variation within than between populations. For example, results of mitochondrial DNA studies show more diversity in one small region of east Africa than in most of Europe. Consequently, any differences in physiology, biochemistry, or anatomy between groups defined solely by skin colour are inapplicable to their source populations, even if the differences noted are indeed genetically determined.The notion of race, therefore, is not an acceptable surrogate for genetics in assessing performance differences between populations. The examples of west and east African athletes and their dominance of track events have propagated the presumption of the genetically endowed natural athlete. Even within these populations, there is clustering of the most successful athletes. More than 80% of the top Kenyan endurance runners, for example, originate from the altitudinous Rift Valley Province, where less than 25% of the population lives. As such, a genetic advantage in a genetically isolated population adapted towards endurance performance seems likely. However, findings of genetics studies do not back this theory.Although genetics might not be the main determinant of population differences in physical performance, evidence is accumulating to suggest an important role of genetics in individual differences in physical performance. At the most fundamental level, various anthropometric measurements, such as height, are highly heritable and, consequently, the potential to become an elite high jumper, or a volleyball or basketball player is under a strong degree of genetic control. However, not all tall individuals will be successful in these events, irrespective of motivational factors. There are many phenotypic requirements to becoming an elite performer, and every phenotype is affected by the genome to varying degrees. An algorithm, incorporating many individual genetic effects, might best describe the overall genetic effect of elite performance and might account for the disparity in findings with respect to the effect of individual performance genes on elite athlete status across a range of sporting events. The sequencing of the human genome and the technological advances that follow could help in the identification of gene variants that make up the elite athlete. However, the screening of these variants alone is unlikely to allow prediction of athletic performance. The overall genetic effect on elite performance might not be a simple sum of the individual gene variants, since environmental factors and genetic background are likely to be confounding factors. Even with the perfect genetic make-up, the environment has to be right for genetic endowment to prevail. Thus, the unique environmental conditions found in east Africa might be optimum for the development of endurance performance.The effect of previously identified genetic variants on elite athlete status is small, but has not deterred some who seek to exploit genetic-performance research. For example, one company has acquired the licence for the putative performance gene α-actinin-3 (ACTN3 is an actin-binding protein expressed in fast twitch muscle fibres) and has already marketed a genetic test that they claim can "… provide an insight into the best event in which to compete in the sport of your choice, so that the individual can obtain the best results for their efforts."The X-allele of ACTN3 confers a premature stop codon and a non-functional ACTN3 protein. These claims are based on a study in which no XX genotypes were identified in Olympic power athletes, in whom a lower X-allele frequency was noted than in the general population. In endurance runners, however, an excess of the X-allele was noted. Although ACTN3 is an interesting candidate gene of physical performance, the use of a genetic test for this one gene to assess potential for athletic success cannot be justified given the multifactorial nature of sporting performance. Others have been persuaded to consider multiple genes when examining multifactorial traits such as physical performance. A professional Australian Rugby team called the Sea-Eagles has, for example, admitted genotyping 18 of their 24 players for 11 exercise-related genes and tailoring exercise training for the individuals on the basis of their results. Although some genes do affect the interindividual variation in physical performance and trainability, this knowledge cannot be used to predict sporting talent or to prepare a training schedule. The current genetic evidence does not warrant genotyping an individual to establish their ability to run fast when this trait can be measured far more effectively with a stopwatch.The search for performance candidate genes is gaining momentum, but remains in its infancy. Even with the most optimistic predictions, which assume further technological advances to allow for the high throughput of samples for genetic analysis, the genes considered important in extreme phenotypes—eg, sprint, power, strength, and endurance—and the way that they interact with other genes and with the environment to create an elite athlete will not be fully understood for many years. The parallels with genetic research into common diseases best illustrate this point; the identification of BRCA1 and BRCA2 certainly adds to the understanding of breast cancer, but these genes alone only account for a small proportion of all cases.As increasing numbers of putative genes of physical performance are discovered, more genetic tests will appear on the market with further claims to attract those desperate to succeed in the sporting arena. Not only could such a development discourage potentially successful athletes who do not possess the desired genotypes, it could also encourage the view that participation in sport is futile unless one has an advantageous genotype. This prospect is a worrying one, particularly in view of the increasing prevalence of sedentary behaviour and physical inactivity-related disorders. The lengths to which athletes will go to gain a competitive edge emerges regularly, with high-profile athletes testing positive for different banned substances, and there is concern that attempts at gene doping (see Feature page S18 ) are inevitable. The successful creation of mighty mice with genetically manipulated insulin-like growth factor 1 concentrations, inducing increased skeletal muscle hypertrophy in response to training, has not gone unnoticed by the athletic community. Such technologies are in their infancy and the lasting effects of gene doping are unknown. Irrespective of the ethical and safety implications, however, the long-term effects of gene doping will inevitably be discovered to the misfortune of those who experiment. Yannis Pitsiladis is a Reader in Exercise Physiology at the Institute of Biomedical and Life Science at the University of Glasgow, and Director of the International Center for East African Running Science. Robert Scott is a final year Doctorate student investigating the genetics of human performance. Compared with primates, people have several anatomical and physiological facets that have evolved over time and that lend themselves to endurance running. Although these adaptations are common to all modern human beings, there are great differences in physical performance between populations. This fact raises the intriguing possibility that certain populations might have further adapted, predisposing them to higher levels of physical performance. The dominance of long-distance running events and sprint events by east African and west African athletes, respectively, is often described as an example of population specialisation, but the extent to which these successes are mediated by genetic variation is unknown. Within all populations, including seemingly specialised populations, there exists large interindividual variation in physical performance. Most people—whether from an urban city like Glasgow, UK, or from the town of Eldoret in rural Kenya, from where a disproportionately high number of Kenyan running legends originate—will recall from their youth some children who seemed to be naturally better at certain sporting events than others. Even at the elite level, only a relatively small number of athletes compared with the number in training will win an Olympic or World Championship medal during their career, though the training regimes of those who do and do not win might be similar, with some even sharing the same coach. There is good evidence that lends support to the theory that athletic capability is inborn, resulting in the disparity in physical performance noted, without excluding the importance of the environment in enhancing any favourable, or overcoming any unfavourable, genetic predisposition. National patterns of success in athletic competition are evident in the medal tally at major competitions. For example, athletes from Ethiopia and Kenya won nine of the 12 available medals for the 5000 m and 10 000 m at the 2003 World Championships in Paris. Furthermore, all male world record holders for athletic events, ranging from the 100 m to the marathon, are of black African ancestry (table). Athletes of west African ancestry hold records for the 100–400 m events, whereas those of east or north African ancestry hold records for the longer distances. Such statistics have led to the presumption that athletes of black skin colour are genetically endowed natural athletes. This notion is based on the preconception that every race, defined solely by skin colour, constitutes a genetically homogeneous group. This idea is contrary to the finding that there is more genetic variation within than between populations. For example, results of mitochondrial DNA studies show more diversity in one small region of east Africa than in most of Europe. Consequently, any differences in physiology, biochemistry, or anatomy between groups defined solely by skin colour are inapplicable to their source populations, even if the differences noted are indeed genetically determined. The notion of race, therefore, is not an acceptable surrogate for genetics in assessing performance differences between populations. The examples of west and east African athletes and their dominance of track events have propagated the presumption of the genetically endowed natural athlete. Even within these populations, there is clustering of the most successful athletes. More than 80% of the top Kenyan endurance runners, for example, originate from the altitudinous Rift Valley Province, where less than 25% of the population lives. As such, a genetic advantage in a genetically isolated population adapted towards endurance performance seems likely. However, findings of genetics studies do not back this theory. Although genetics might not be the main determinant of population differences in physical performance, evidence is accumulating to suggest an important role of genetics in individual differences in physical performance. At the most fundamental level, various anthropometric measurements, such as height, are highly heritable and, consequently, the potential to become an elite high jumper, or a volleyball or basketball player is under a strong degree of genetic control. However, not all tall individuals will be successful in these events, irrespective of motivational factors. There are many phenotypic requirements to becoming an elite performer, and every phenotype is affected by the genome to varying degrees. An algorithm, incorporating many individual genetic effects, might best describe the overall genetic effect of elite performance and might account for the disparity in findings with respect to the effect of individual performance genes on elite athlete status across a range of sporting events. The sequencing of the human genome and the technological advances that follow could help in the identification of gene variants that make up the elite athlete. However, the screening of these variants alone is unlikely to allow prediction of athletic performance. The overall genetic effect on elite performance might not be a simple sum of the individual gene variants, since environmental factors and genetic background are likely to be confounding factors. Even with the perfect genetic make-up, the environment has to be right for genetic endowment to prevail. Thus, the unique environmental conditions found in east Africa might be optimum for the development of endurance performance. The effect of previously identified genetic variants on elite athlete status is small, but has not deterred some who seek to exploit genetic-performance research. For example, one company has acquired the licence for the putative performance gene α-actinin-3 (ACTN3 is an actin-binding protein expressed in fast twitch muscle fibres) and has already marketed a genetic test that they claim can "… provide an insight into the best event in which to compete in the sport of your choice, so that the individual can obtain the best results for their efforts." The X-allele of ACTN3 confers a premature stop codon and a non-functional ACTN3 protein. These claims are based on a study in which no XX genotypes were identified in Olympic power athletes, in whom a lower X-allele frequency was noted than in the general population. In endurance runners, however, an excess of the X-allele was noted. Although ACTN3 is an interesting candidate gene of physical performance, the use of a genetic test for this one gene to assess potential for athletic success cannot be justified given the multifactorial nature of sporting performance. Others have been persuaded to consider multiple genes when examining multifactorial traits such as physical performance. A professional Australian Rugby team called the Sea-Eagles has, for example, admitted genotyping 18 of their 24 players for 11 exercise-related genes and tailoring exercise training for the individuals on the basis of their results. Although some genes do affect the interindividual variation in physical performance and trainability, this knowledge cannot be used to predict sporting talent or to prepare a training schedule. The current genetic evidence does not warrant genotyping an individual to establish their ability to run fast when this trait can be measured far more effectively with a stopwatch. The search for performance candidate genes is gaining momentum, but remains in its infancy. Even with the most optimistic predictions, which assume further technological advances to allow for the high throughput of samples for genetic analysis, the genes considered important in extreme phenotypes—eg, sprint, power, strength, and endurance—and the way that they interact with other genes and with the environment to create an elite athlete will not be fully understood for many years. The parallels with genetic research into common diseases best illustrate this point; the identification of BRCA1 and BRCA2 certainly adds to the understanding of breast cancer, but these genes alone only account for a small proportion of all cases. As increasing numbers of putative genes of physical performance are discovered, more genetic tests will appear on the market with further claims to attract those desperate to succeed in the sporting arena. Not only could such a development discourage potentially successful athletes who do not possess the desired genotypes, it could also encourage the view that participation in sport is futile unless one has an advantageous genotype. This prospect is a worrying one, particularly in view of the increasing prevalence of sedentary behaviour and physical inactivity-related disorders. The lengths to which athletes will go to gain a competitive edge emerges regularly, with high-profile athletes testing positive for different banned substances, and there is concern that attempts at gene doping (see Feature page S18 ) are inevitable. The successful creation of mighty mice with genetically manipulated insulin-like growth factor 1 concentrations, inducing increased skeletal muscle hypertrophy in response to training, has not gone unnoticed by the athletic community. Such technologies are in their infancy and the lasting effects of gene doping are unknown. Irrespective of the ethical and safety implications, however, the long-term effects of gene doping will inevitably be discovered to the misfortune of those who experiment. Yannis Pitsiladis is a Reader in Exercise Physiology at the Institute of Biomedical and Life Science at the University of Glasgow, and Director of the International Center for East African Running Science. Robert Scott is a final year Doctorate student investigating the genetics of human performance. Yannis Pitsiladis is a Reader in Exercise Physiology at the Institute of Biomedical and Life Science at the University of Glasgow, and Director of the International Center for East African Running Science. Robert Scott is a final year Doctorate student investigating the genetics of human performance. Yannis Pitsiladis is a Reader in Exercise Physiology at the Institute of Biomedical and Life Science at the University of Glasgow, and Director of the International Center for East African Running Science. Robert Scott is a final year Doctorate student investigating the genetics of human performance.