Genetics and the success of East African distance runners (Editor's selection)

Non-genetic studies of East African runners

Non-genetic explanations for the success of East African runners in international athletics include the suggestion that they enjoy a psychological advantage mediated through stereotype threat ⁵, or that the distances East Africans ran to school as children served them well for subsequent athletic success ^2;6. It has recently been shown that elite East African distance runners travelled long distances to school as children and mostly by running ^1;2; many travelling phenomenal distances such as upwards of 20 km each day. A study by Saltin et al.⁶ has also shown that East African children who had used running as a means of transport to school had a maximum oxygen uptake (VO₂ max) some 30% higher than those who had not, therefore implicating distance travelled to school as one of the determinants of East African running success. Regional disparities in the production of Ethiopian and Kenyan middle- and long-distance runners have been shown ^1;2. In a study of the demographic characteristics of elite Ethiopian athletes, 38% of the elite marathon runners were from the region of Arsi, which accounts for less than 5% of the Ethiopian population ². As shown in Figure 1, these findings were mirrored in Kenya, where 81% of the best Kenyan runners originated from the Rift Valley province, which accounts for less than a quarter of the Kenyan population¹. Although some believe that this geographical disparity is mediated by an underlying genetic phenomenon ^3;4, it is worth considering that these regions are altitudinous, even relative to the rest of East Africa ^1;2, and that endurance athletes have long used altitude training to enhance endurance performance. The rationale behind altitude training is that the lower oxygen levels elicit further positive haematological adaptations to improve oxygen transport and benefit endurance performance (for review, see Wilber et al. ⁷). Although it is presently unclear how this applies to indigenous altitude dwellers, it has been suggested that endurance training and altitude combine synergistically in those native to moderate altitude to partially account for the success of East African athletes ⁸. Of course, the altitude challenge that individuals in these regions have faced may be a selection pressure shaping the inhabitants towards aerobic performance, as discussed below.

The concurrent success of athletes of West African ancestry in sprint-based events has augmented the idea of ‘black’ athletic supremacy. This idea has arisen due to the belief that similar skin colour indicates similar genetics. As such, a number of studies have compared physiological characteristics such as VO₂max, lactate accumulation and running economy between groups of ‘black’ and ‘white’ athletes. In one of these studies, ‘black’ South African runners were found to have lower blood lactate levels than ‘white’ runners for given running intensities ^9-11. It was also shown that ‘black’ athletes had better running economy ¹² and higher fractional utilisation of VO₂ max at race pace ^9;10;12. On the one hand, some studies comparing athletes of differing skin colour conclude that their results may explain the success of ‘black’ athletes in distance running events ¹², while other studies present arguments compatible with the idea that ‘blacks’ are better suited to events of short duration ¹³. These contradictions highlight the problem associated with grouping athletes based simply on skin colour. Furthermore, it is not clear to what extent findings in ‘black’ South African runners can be extrapolated to account for the success of East African runners.

The first published study of elite Kenyan athletes was undertaken by Saltin et al. ⁶ who compared a number of physiological characteristics that could potentially influence athletic performance, such as VO₂max and lactate accumulation, between elite Scandinavian and Kenyan runners. It was found that Kenyan runners had lower lactate and ammonia accumulation during high-intensity exercise. Superior running economy was also reported in Kenyan runners, yet VO₂ maxwas not different when compared to Scandinavian runners. In another study by Saltin et al. ¹⁴, skeletal muscle fibre type distribution did not differ in elite Kenyan runners (senior and junior) from their Scandinavian counterparts, although the senior Kenyan runners had a tendency for higher muscle capillarity than the Scandinavian runners. However, the Kenyan junior runners had lower muscle capillarity than both the Scandinavian and Kenyan seniors ¹⁴ suggesting that training and not genetic endowment was more likely to be responsible for the tendency of senior Kenyan runners to have higher muscle capillarity. These initial studies of elite Kenyan athletes by Saltin et al.^6;14 demonstrate that factors such as increased childhood physical activity and hard training are probably the major contributors to the superior performances of Kenyan runners. Despite these findings, assertions remain that East Africans have the ‘proper genes’ for distance running ¹⁵. As many of the top Kenyan runners are from rural areas rather than built up towns and cities ^1;15, a recent study by Larsen et al. ¹⁶ investigated the extent to which the VO₂max training response differed between Nandi town and village boys. This study was designed to investigate if the trainability of VO₂max, which has been shown to be genetically influenced ¹⁷, was greater in the Nandi boys from rural areas compared to those from town. No difference was found between the increase in VO₂max of town and village boys, while the magnitude of the training response was similar to that previously reported in Caucasian boys ¹⁸. These findings may serve to demystify the success of the Nandi runners ¹, showing that they may not have an obvious genetic advantage in aerobic capacity or its trainability. An additional finding that opposes genetics as the primary factor for the geographical imbalance in athlete production was that the rural boys were more physically active than the urban boys ¹⁹. Clearly, increased childhood physical activity levels are strongly implicated in the success of East African runners in international competition.

Human genetic variation and studies of African runners

Although basic and applied physiological studies are required to better understand the factors influencing elite performance, the approach of comparing physiological characteristics between groups defined solely by skin colour does not offer much insight into why some groups are more successful than others. Even within groups of individuals of similar skin colour, many ethnic and tribal groups exist. For example, over 70 languages are in everyday use in Ethiopia, while in Kenya, over 50 distinct ethnic communities speak close to 80 different dialects. The inadequate classification of subjects into groups based on characteristics such as skin colour will undoubtedly lead to equivocal results and serve only to augment existing stereotypes of genetically advantaged black athletes. Studies comparing ‘black’ and ‘white’ athletes ^6;14 offer some insight into the physiological determinants of elite performance and differences between the groups of African and Caucasian runners tested, but little, if any, insight into any genetic influences on the disproportionate success of East African runners. Despite the perpetuation of the idea that ‘black’ athletes are genetically adapted for athletic performance ²⁰, until recently, no studies had attempted to assess this hypothesis ^21-23. The concept of ‘black’ athletic superiority is based on a preconception that each race constitutes a genetically homogeneous group, with race defined simply by skin colour. This belief is contrary to the assertion that there is more genetic variation among Africans than between African and Eurasian populations ²⁴.

The genetics of race is controversial and gives rise to a number of contrasting viewpoints, with particular emphasis on the use of race as a tool in the diagnosis and treatment of disease. Some argue that there is a role for race in biomedical research and that the potential benefits to be gained in terms of diagnosis, treatment and research of disease outweigh the potential social costs of linking race or ethnicity with genetics ²⁵. Others, however, advocate that race should be abandoned as a tool for assessing the prevalence of disease genotypes, and that race is not an acceptable surrogate for genetics in assessing the risk of disease and efficacy of treatment in human populations ²⁶. Arguments for the inclusion of race in biomedical research often focus on its use to identify single gene disorders and their medical outcome, but the genetic basis of complex phenotypes such as athletic performance is poorly understood and more difficult to study. It is estimated that most human genetic variation is shared by all humans and that a marginal proportion is specific to major continental groups ²⁷. Recent data from the HapMap study, which aims to characterise human genetic variation by genotyping African, Asian and European individuals, show values between 7 and 12% of total genetic variation attributable to between-population differences. Similarly, the data shows that haplotypes (linked segments of genetic variation, rarely subject to reassortment by recombination) are shared across populations ²⁸. Indeed, the level of genetic diversity between human populations is not large enough to justify the use of the term ‘race’ (see Jobling et al. ²⁹ for a review). Consequently, any differences in physiology, biochemistry and/or anatomy between groups defined solely by skin colour (e.g. comparing ‘black’ with ‘white’) are not directly applicable to their source populations, even if the differences found are indeed genetically determined.

Potential genetic determinants of East African running success

The capacity of Homo sapiens for endurance running (defined as the ability to sustain running for extended periods of time using primarily aerobic metabolism), although not comparable to other mammalian endurance specialists, is unique among the primates. This has led to the belief that endurance capabilities have been central to the recent evolutionary history of modern humans ³⁰. The unique endurance capacity of humans relative to the other primatesis purported to be due to a number of traceable adaptations beneficial to endurance running in the Homo genus ³⁰. Although anatomically modern humans are young in evolutionary terms (~150,000 years) relative to the age of the Homo genus (~2 million years), human populations began to diverge into new environments outside Africa ~70,000 years ago ³¹. It is possible, therefore, that divergent human populations (in different continents for a significant portion of the age of the species) have accrued varying degrees of these adaptations due to different selection pressures, further specialising them for an endurance phenotype or otherwise. The varying adaptation to hypobaric hypoxia by geographically isolated populations represents a well-studied example of this and may relate to endurance performance. Andean highlanders display higher levels of haemoglobin and saturation than Tibetans at similar altitude, while Ethiopian highlanders maintain oxygen delivery despite having haemoglobin levels and saturation typical of sea level ranges ³². There has been much conjecture surrounding such adaptations to altitude and their role in the evolution of human physiological responses ^33,34. Given the origin of modern humans in East Africa: a higher, drier and cooler environment than more distant ancestors may have inhabited, the ancestral form of modern humans would have been well adapted for altitude tolerance and presumably, endurance performance, as the phenotypes are similar ³⁴. If the ancestral form developed in the highlands of East Africa was indeed an altitude/endurance phenotype, East Africans may have further developed an up-regulated, high capacity version through having remained in the same environment ³⁴, thus favouring them further for endurance performance. Other populations may have ‘diluted’ the ancestral phenotype, or developed down-regulated, low-capacity versions through selection for other phenotypes on migration to new environments (e.g. Andean and Tibetan populations) ³⁴. Some insight was offered into this intriguing hypothesis in the first genetic studies of elite East African runners, using uni-parentally inherited genetic markers to investigate the ancestral origins of many of the world’s best middle- and long-distance runners.

Genetic studies of African runners

Polymorphisms in mitochondrial DNA (mtDNA) have been suggested to influence variation in human physical performance, as mtDNA encodes various sub-units of enzyme complexes of oxidative phosphorylation, as well as components of the mitochondrial protein synthesis system ³⁵. mtDNA is inherited in its entirety from mother to child, only changing as new mutations arise, resulting in the accumulation of linked complexes of mutations down different branches of descent from a single ancestor: ‘Mitochondrial Eve’ (Figure 2). This linear pattern of inheritance can also be used to trace the ancestral origins of individuals or populations ³⁶ and construct phylogenetic trees back to ‘Mitochondrial Eve’ (each branch of the tree is known as a haplogroup). The frequency of these haplogroups can be used to trace population movements and expansions, and, as such, different haplogroups are at widely varying frequencies in different regions ³⁷. A simplified version of a mtDNA phylogeny is shown in Figure 2. mtDNA analysis was recently applied to the cohort of elite Ethiopian distance runners ²². Rather than the elite Ethiopian runners being restricted to one area of the tree, results revealed a wide distribution, similar to the general Ethiopian population ^22;37-40 (Figure 2) and in contrast to the concept that these elite runners are a genetically distinct group as defined by mtDNA. Furthermore, the diversity of mtDNA haplogroups found in the elite runners does not support a role for mtDNA polymorphisms in their success. It can be seen from Figure 2 that some of the athletes share a more recent common mtDNA ancestor with many Europeans. This finding does not support the hypothesis that the Ethiopian population from which the athletes are drawn have remained genetically isolated in East Africa but shows that they have undergone migration events during the age of the species. This is in contrast to the possibility that Ethiopian athletes have maintained and further developed the ancestral endurance phenotype through having remained isolated in the East African highlands. It is likely that population movements within Africa as recently as a few thousand years ago have contributed to the peopling of East Africa, through the eastern path of the Bantu migrations ^37;41. However, linguistic data show that Bantu languages are absent in Ethiopia ², but frequent in Kenya ¹, showing that the neighbouring regions may have been subject to widely different patterns of migration. Recent data on the mtDNA haplogroup frequencies of the Kenyanpopulation ⁴² and elite Kenyan runners ⁴³ reveal that the mtDNA haplogroups found in Kenya are very different to those found in Ethiopia and show a higher frequency of African specific haplogroups. Collectively, these findings imply that the phenomenon of East African running should best be considered as two distinct phenomena, that of Ethiopian and Kenyan success, at least from a genetic viewpoint.

Theoretical framework for genetic advantage of African runners

For genetic selection to occur in a population there must be pre-existing genetic variation coding for phenotypic variation, or new variants must arise in a population by mutation which confer a different level of evolutionary fitness on the bearer. A particular variant conferring improved endurance performance is likely to increase in frequency in the population as long as having good endurance performance provides improved ‘Darwinian fitness’. Given that the regions of East Africa which produce many athletes are populated by a genetically diverse population, who appear not to have been isolated for long periods of time (relative to the age of our species), it is less likely that a unique genetic predisposition to endurance performance has evolved, as there has been less time for either selection or genetic drift to increase the frequency of hypothetical ‘performance alleles’. However, it must be acknowledged that although the levels of ancestral diversity in these East African regions reduce the likelihood of such a theoretical framework for genetic selection to have occurred for endurance performance, the potential for one remains, and future work will continue to investigate this possibility. For example, if the advantage offered by a particular genetic variant is large enough, that allele can rapidly increase in frequency within the population ⁴⁶. For example, the previously mentioned evidence of different strategies to cope with hypobaric hypoxia ³³ used by geographically isolated indigenous populations may suggest that rather than it being an ancestral phenotype, strategies to cope with altitude may have developed separately in isolated populations ³³. Therefore, the possibility exists that environmental pressure in the form of hypobaric hypoxia has more recently (in the last few thousand years rather than the last 150,000) caused selection for variants conferring advantage in oxygen utilisation and subsequently increased the frequency of these variants in moderate altitude populations. In the moderate altitude populations of Ethiopia and/or Kenya, such adaptations may have the potential to concurrently influence the endurance phenotype ³⁴. Although unlikely to be isolated to East Africans, it is entirely possible that changes in the frequency of particular candidate genes for human performance would have an influence on East African success. For example, a key performance gene, alpha-actininin-3 (ACTN3), which has been associated with elite physical performance ⁴⁷ is at widely differing frequencies in different populations ⁴⁸. However, endurance performance is a complex phenotype, reliant upon the successful integration of a number of physiological, biochemical, and biomechanical systems, which themselves are the product of a multitude of contributors. The success of East African runners is very unlikely to be the result of a single gene polymorphism; rather it is likely that elite athletes rely on the presence of a combination of advantageous genotypes at a multitude of loci.

To date, only one study has investigated the frequency of a nuclear candidate gene for human performance in East African athletes ²³. The gene studied was the Angiotensin converting enzyme (ACE) gene: the most studied of the putative candidate genes for human performance, where an insertion polymorphism (I) is associated with lower levels of circulating and tissue ACE than the deletion (D) ^49;50. The ACE gene has been associated with a number of aspects of human performance, reviewed elsewhere ^51;52. In general, the I allele has been associated with endurance type performance and the D allele with power type performance. Intriguingly, the ACE I allele has also been associated with altitude tolerance ⁵³ making it an ideal candidate gene to investigate in East African athletes given the suggestion that the altitude at which these athletes live and train may partially account for their success ⁸. As such, ACE I/D genotype frequencies were tested in elite Kenyan athletes relative to the general population ²³. Based on previous findings⁵¹, it may have been expected that the elite runners would show an excess of the I allele. However, no significant differences were found in I/D genotype frequencies between athletes and the general population ²³. Different levels of linkage disequilibrium in Africans and Caucasians ^54;55 meant that an additional, potentially causal variant (A22982G) was tested. However, no significant differences in A22982G genotype frequencies were found between athletes and the general population ²³. Indeed 29% of Kenyan controls and only 17% of international Kenyan athletes had the putatively advantageous ‘AA’ genotype (always found in concert with II in Caucasians) for endurance performance. While controversy over the influence of ACE genotype on endurance performance continues ⁵³, this study did not support a role for ACE gene variation in explaining the East African distance running phenomenon. Whether other nuclear variants are involved remains to be determined. Currently, studies are underway to investigate the frequency of other candidate variants in these unique cohorts of East African athletes ^1;2 which may shed more light on the question. New technologies that allow the screening of thousands of variants in one experiment will assist this process.

Conclusions

The limited studies presented above constitute the only available work to date on the genetics of the African running phenomenon and show that the athletes, although arising from distinct regions of East Africa, do not arise from a limited genetic isolate. For example, the Y chromosome types found in excess in elite Ethiopian athletes are also found outside Africa. Other findings suggest that the most studied of the previously identified performance genes (i.e. ACE), does not appear to influence the success of East African athletes, which highlights another important point surrounding the genetics of exercise performance: in no study to date has a cohort of elite athletes all shown the same genotype. It may be the case that a particular genetic variant is more frequent in the elite athletes relative to a non-athlete population, which may satisfy the statistical requirement of P < 0.05, but the biological importance of such a statistical boundary remains to be elucidated. It also serves to highlight the fact that there are many paths to success and that one can overcome a potentially disadvantageous genotype. It is likely that any single gene variant that offers advantage influences the fine-tuning of performance rather than simply conferring success or failure. Any of these potentially advantageous gene variants are likely to be found in excess amongst elite athletes but the exact combinations needed for international success remain unknown. It is perhaps unlikely that East Africa is producing unique genotypes that cannot be matched by those from other areas of the world, but more likely that those in East Africa with an advantageous genotype realise their advantage through having used it regularly. It is interesting that Ethiopia and Kenya do not share a similar genetic ancestry, as defined by mtDNA ^22;43, but what they do share is a similar environment: moderate altitude and high levels of physical activity. Few other regions of the world have such high levels of childhood physical activity combined with such cultural/financial importance being placed on distance running. This information clearly implicates environmental factors as being more influential than genetic factors in the success of East African distance runners. In an economically deprived region such as East Africa, economic factors also provide an additional motivation, if not a necessity, to succeed in distance running. In summary, it is unjustified at present to regard the phenomenon of East African running success as genetically mediated; to justify doing so one must identify the genes that are important. To do so also disregards the intense training regimens for which East African athletes are famous ⁵⁶.

Address for correspondence:

Dr YP Pitsiladis, International Centre for East African Running Science (ICEARS), Faculty of Biomedical and Life Sciences (IBLS), University of Glasgow, Glasgow G12 8QQ, UK.

Tel.: +44 (141) 330 3858

Fax: +44 (141) 330 2915

Email: Y.Pitsiladis@bio.gla.ac.uk

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* Corresponding author. Address at the end of text.

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