Genetics Flashcards
What is a genotype?
describes the genetic make-up of an individual
What is a phenotype?
describes the physical expression of these genes e.g. height, weight, strength, endurance etc.
Phenotype is consequent to the interaction of the genotype with the physical environment
When does an athletic phenotype show?
An athletic phenotype occurs where an ‘athletic genotype’ interacts with appropriate environmental stimuli to produce high-level performance in the chosen physical activity i.e. nature and nurture
how much can VO2max vary between individuals?
Over 100%
What might genetics change in individuals with an athletic genotype?
that muscle oxidative enzyme activity adapted in response to exercise training: “…the differences between the respiratory enzyme levels of active and inactive muscles might be due not only to genetic differences but also to an adaptive process.”
What is the difference in rats bread for endurance training?
Endurance performance is >300% greater in HCR vs LCR (measured at generation 11)
Skeletal muscle fibre number is ~35% greater in HCR vs LCR with average muscle fibre area being ~35% smaller, and with a greater capillary density (generation 15)
Citrate synthase and b-HAD activity were ~40% greater and PFK ~30% lower in HCR vs LCR (generation 15)
VO2max was ~50% greater in HCR vs LCR (generation 15)
What do the data suggest about heratibility of performance?
There is a genetic predisposition for running performance
What was run concurrently with inherited running capacity?
Reduced CVD and mortality factors
What negative effects were seen in the low capacity running group?
Increased mean arterial blood pressure Decreased arterial responsiveness Increased free fatty acids (94%) Circulating triglycerides (168%) Circulating insulin (131%) Fasting blood glucose (20%)
Transcription factors for mitochondrial biogenesis and oxidative enzymes were also reduced
The increased cardiovascular risk suggests a strong association between physical fitness and chronic disease via impairment of mitochondrial function
What is the advantage of an ability too adapt?
Since, natural environments are not constant, those individuals with greater capacity to adapt may have selective advantages in survival and reproduction. This shows that the ability too adapt to a stimuli e.g. exercise is an important factor for survival
As phenotypes that were more fit for existence are more likely to be selected, it is expected that the ability to adapt to environmental stimuli would be a preserved trait
What environmental stimuli was present during human evolution?
Exercise
What is renin?
Renin is released from the kidney under conditions of salt, blood volume loss, and sympathetic nervous activity, and cleaves angiotensinogen to produce angiotensin I (Ang I)
What is the importance of Ang I and II?
Ang I is the substrate for the angiotensin-converting-enzyme (ACE) to produce angiotensin II (Ang II). Ang II is a potent vasoconstrictor and is therefore important in regulating blood flow (nutrient delivery) and blood pressure
Ang II increases the breakdown of bradykinin (bradykinin stimulates muscle blood flow, glucose extraction, muscle protein synthesis and aids efficiency). High bradykinin are beneficial to adaption but high Ang II is maladaptive to training
What is the ACE polymorphism?
A common polymorphism in the ACE gene is a 287 base sequence insertion (I) or deletion (D): The D allele is associated with greater ACE activity i.e. a higher vasoconstrictive potential. Individuals with the D polymorphism would have reduced response to exercise training but those with allel I should respond better too training
Reduced incidence of the DD genotype was found in 25 elite mountaineers vs controls; and I allele frequency was greater in 91 Olympic endurance vs sprint athletes
One gene it unlikely to be wholly responsible for an individual’s capacity and responsiveness
What was shown in individuals with the II ace genotype?
A study of 123 male army recruits undergoing a standardised exercise training programme showed that those with the II ACE genotype had greater anabolic and efficiency response to training than those with the ID or DD ACE genotypes [II = better ‘trainability’]
What do ACE inhibitors do?
ACE inhibitors (ACEIs) reduce circulating ACE and therefore have an analogous effect to that of I allele expression
What happens in muscle with high-fat/low glucose?
muscle with high-fat/low-glucose results in an increased exercise-induced PDH kinase expression (conserving muscle glycogen)
Where might some of the benefit imparted by ACEIs come from?
Some of the benefit imparted by ACEIs may relate to conservation of energy (improved efficiency) under conditions of reduced nutrient and/or oxygen flow to the periphery
Who should be used as control groups?
Physically active individuals
Research studies and clinical trials should use physically active (or even elite athlete) populations as the “control group” for investigations, because sedentary subjects are exposed to a ‘sub-optimal’ environmental stimulus and may express maladaptations
What is athletic capability linked with?
There is a strong association between athletic capability – both genetically endowed and environmentally enhanced – and health
This link supports prescription of physical activity as a preventative measure for chronic disease
What is the difference between endurance training for 8 weeks and 7 generations of selective breeding?
8 weeks of exercise training show larger changes than selective breeding. THis shows that the adaptability of the muscle is larger than the ability of the genotype to be bread
What are the principles of training?
Training adaptations require system overload, are task specific and reversible
For skeletal muscle, exercise converts the mechanical signal during contraction into a molecular response to?
Phosphorylation of nuclear transcription factors
Increased mRNA synthesis (typically) - peaking 1-8 hours after exercise
Protein synthesis - because protein half-life is longer than mRNA, transient mRNA increases have long lasting effects of protein expression
Induce a phenotypic adaptation
Therefore, repeated exercise (e.g. daily) has a cumulative effect on protein expression
What genes does one bout of resistance training stimulate?
One bout of resistance exercise causes rapid activation of several genes involved with muscle hypertrophy, but which revolve around the phosphatidylinostol 3-kinase (PI3-k)-Akt-mammalian target of rapamycin: mTOR
What does mTOR inhibit?
mTOR inhibits cellular autophagy which is a state of protein degradation to scavenge amino acids when the nutrient state is low
What happens during acute exercise to mTOR activation?
During acute exercise AMPK is activated due to an increase in the AMP/ATP ratio, and AMPK inhibits mTOR, allowing amino acids to be available as fuel for exercise. So acute activation of AMPK will result in a response to exercise by reducing ATP use and creating more AP e.g. AMPK= increased glucose uptake and increased fatty acid oxidase .
When AMP is high and ATP low AMP activates AMPK by dislodging ATP from the alpha subunit and making it more sensitive to phosphorylation by AMP kinases
In skeletal muscle the main AMPK kinase is LKP1 but there are other factors that may active AMPK.
So training increases in AMPK should be beneficial for endurance performance
What happens to mTO activation once exercise is stopped?
Once exercise is completed however, AMPK activity quickly returns to basal values, mTOR inhibition is reversed and autophagy reduced promoting protein synthesis via phosphorylation of p70s6k. Therefore activation in mTOR pathway is crucial in increasing protein synthesis post resistance training
What is Mitochondrial protein turnover half-life?
1 week
How much can endurance training increase mitochondrial protein content by?
100% within 6 weeks
What does blocking blocking calmodulin-dependent protein kinase (CaMK) or calcineurin do?
Blocks mitochondrial biogenesis
What factor is increased after endurance training?
PGC1-a and is required for mitochondrial biogenesis to occur
What is mitochondrial biogenesis modulated by?
- expression of nuclear respiratory factor 1 (NRF-1; that regulates mitochondrial DNA transcription)
- Peroxisome proliferator-activated receptor gamma (PPAR-g; that regulates the expression of mitochondrial b-oxidation enzymes),
- Nuclear factor of activated T-cells (NFAT; required in the nucleus for transcription)
Overall what happens in resistance training?
increases the phosphoylation state of the mTOR signalling pathway with a small effect on the AMPK pathway
Overall what happens post endurance exercise?
Endurance exercise causes a sustained increase in AMPK phosphorylation and PGC-1a protein expression; and Calcineurin/CAMK to increase nuclear translocation of NFAT.
THe NAFT pathway has been shown to increase type I fiber expression, myosin heavy chain (fatigue resistant), CAMK and calcineurin. It may also act as a signalling pathway for increasing PGC1a and mitochondrial biogenesis
What did Atherton and colleagues suggest?
an “Akt-AMPK master-switch” from the observation that AMPK and Akt phosphorylation were reciprocal during high/low frequency stimulation of animal muscle. So energy in response to resistance training should be directed to increasing muscle contracting proteins. Whereas energy in response to endurance should be directed into making mitochondria and fatigue resistant proteins. The master switch therefore may ihbit cross talk between the pathways and provide an explanation for the differentiation of pathways and provide an explanation for the differentiation of the training responses to resistance and endurance exercise
What is genetic endowment for athletic capability associated with?
Genetic endowment for athletic capability is associated with low blood pressure, reduced circulating lipids, lower circulating insulin and blood glucose and increased expression of mitochondrial biogenic genes
What are training responses modulated by?
factors such as ACE gene polymorphism and nutrition
What is the II rather than ID or DD ACE genotype associated with?
The II (rather than the ID or DD) ACE genotype is associated with greater athletic capability and enhanced responses to exercise training
