Genomics and genetics in the biology of adaptation to exercise

Abstract

This article is devoted to the role of genetic variation and gene-exercise interactions in the biology of adaptation to exercise. There is evidence from genetic epidemiology research that DNA sequence differences contribute to human variation in physical activity level, cardiorespiratory fitness in the untrained state, cardiovascular and metabolic response to acute exercise, and responsiveness to regular exercise. Methodological and technological advances have made it possible to undertake the molecular dissection of the genetic component of complex, multifactorial traits, such as those of interest to exercise biology, in terms of tissue expression profile, genes, and allelic variants. The evidence from animal models and human studies is considered. Data on candidate genes, genome-wide linkage results, genome-wide association findings, expression arrays, and combinations of these approaches are reviewed. Combining transcriptomic and genomic technologies has been shown to be more powerful as evidenced by the development of a recent molecular predictor of the ability to increase VO2max with exercise training. For exercise as a behavior and physiological fitness as a state to be major players in public health policies will require that the role of human individuality and the influence of DNA sequence differences be understood. Likewise, progress in the use of exercise in therapeutic medicine will depend to a large extent on our ability to identify the favorable responders for given physiological properties to a given exercise regimen.

Figure 1

An example of a basic univariate genetic path model in monozygotic (MZ) and dizygotic (DZ) twins.

Figure 2

Comparison of distances run by the 11inbred strains of rats. From Barbato JC et al. “Spectrum of aerobic endurance running performance in eleven inbred strains of rats.” J Appl Physiol, 1998, 85(2): 530–536. By permission of the American Physiological Society.

Figure 3

Family lines with low and high VO₂max phenotypes in the sedentary state based on data from the HERITAGE Family Study. From Bouchard C, Daw EW, Rice T, Perusse L, Gagnon J, Province MA, Leon AS, Rao DC, Skinner JS, Wilmore JH. “Familial resemblance for VO₂max in the sedentary state: the HERITAGE family study.” Med Sci Sports Exerc 1998; 30(2), 252–258. Reproduced with permission from Wolters Kluwer Health.

Figure 4

Human variation in vastus lateralis percent type I fibers among sedentary adults. Adapted from Simoneau JA and Bouchard C, “Human variation in skeletal muscle fiber type proportion and enzyme activities.” 1989, Am J Physiol, 257: E567–572. By permission of the American Physiological Society.

Figure 5

Estimates of sources of causal variation in proportion of type I fibers in human skeletal muscle among sedentary people. Reproduced, by permission, from J.A. Simoneau and C. Bouchard, 1995, “Genetic determinism of fiber type proportion in human skeletal muscle,” FASEB J, 9(11): 1091–1095.

Figure 6

Distribution of training responses in VO₂max in individuals of the HERITAGE Family Study. From Bouchard C and Rankinen T. “Individual differences in response to regular physical activity.” 2001 Med Sci Sports Exerc 33(6 Suppl), S446-S451. Reproduced with permission from Wolters Kluwer Health.

Figure 7

The individual changes in heart rate and stroke volume at 50 watts and at 60% of VO₂max on cycle ergometer tests before and after 20 weeks of exercise training. These subjects were Blacks and Whites of the HERITAGE Family Study. From (39) Bouchard C, Rankinen T. Genetic Determinants of Physical Performance. In: RJ Maughan, editor. Olympic Textbook Science in Sport. Wiley-Blackwell, Hoboken, NJ; chapter 12, p 181–201, 2009. Reproduced with permission from Wiley-Blackwell.

Figure 8

Training changes in VO₂max among 10 pairs of MZ twins subjected to a standardized 20-week exercise training program. Adapted from D. Prud’homme et al, 1984, “Sensitivity of maximal aerobic power to training is genotype dependent,” Medicine and Science in Sports and Exercise, 16: 489–493. Reproduced from Bouchard C, Dionne FT, Simoneau JA, Boulay MR. 1992, “Genetics of aerobic and anaerobic performances” Exercise and Sport Sciences Reviews 20:27–58 by permission from Wolters Kluwer Health.

Figure 9

Familial aggregation of VO₂max changes in response to exercise training in the sample of Whites of the HERITAGE Family Study. From Bouchard C, An P, Rice T, Skinner JS, Wilmore JH, Gagnon J, Perusse L, Leon AS, Rao DC. “Familial aggregation of VO₂max response to exercise training: results from the HERITAGE Family Study.” 1999 J Appl Physiol 87: 1003–1008. By permission of the American Physiological Society.

Figure 10

The main classes of small-scale mutations.

Figure 11

Angiotensin-converting enzyme (ACE) I/D polymorphism is associated with left ventricular mass training response. Reproduced, with permission, from (254) T. Rankinen and C. Bouchard, 2005, Genes, genetic heterogeneity, and exercise phenotypes, In Molecular and cellular exercise physiology, edited by F.C. Mooren and K. Volker (Champaign, IL: Human Kinetics), 50. Adapted from H.E. Montgomery et al., 1997, “Association of angiotensin-converting enzyme gene I/D polymorphism with change in left ventricular mass in response to physical training.” Circulation 96: 741–747, and S.G. Myerson et al., 2001, “Left ventricular hypertrophy with exercise and ACE gene insertion/deletion polymorphism: A randomized controlled trial with losartan.” Circulation 103: 226–230.

Figure 12

Positional cloning of a HR50 training response QTL on chromosome 2q34 in the HERITAGE Family Study. From Rankinen T, Argyropoulos G, Rice T, Rao DC, Bouchard C. CREB1 is a strong genetic predictor of the variation in exercise heart rate response to regular exercise: The HERITAGE Family Study. Circ Cardiovasc Genet. 3(3):294–9, 2010. Reproduced with permission from Wolters Kluwer Health.