Week 7: Molecular basis for adaptation to exercise Flashcards
Molecular basis for adaptation to exercise
What theories did the follow people determine?
- Charles Darwin
- Gregor Mendel
- Friedrich Miescher
- Barbara McClintock
Charles Darwin
*Developed the theory of evolution based upon observations of natural selection
* Observed distribution & continuation of animal & plant phenotype in response to their environment – “Survival of the fittest”
* Theory explained adaptive modifications in response to environmental stressors for preservation of species
Gregor Mendel
* Discovered hereditary characteristics of plants and effect of genetics on traits
* Through selective breeding and monitoring developed over 10,000 varieties of pea plants
* Identified dominant and recessive genotypes and how these determine phenotype
Friedrich Miescher (1844-1896) & Phoebus Levene (1869-1940)
* Miescher was first to identify DNA, extracting nuclei from white blood cells
* Levene conducted important work on the nucleic acids, the building blocks of DNA
* Findings helped pave the way toward our understanding of DNA and RNA as the key elements in the maintenance of life
Barbara McClintock (1902-1992)
* Discovered so-called “jumping genes” or the phenomenon of genetic transposition within the genome
* Showed how certain genes were responsible for turning on and off physical characteristics
* Developed early theories of epigenetics – the suppression of expression of genetic information in response to various stimuli/stress
What theories did the follow people determine?
Rita Levi-Montaclini
* Discovered and characterised nerve growth factor
* Identified its importance in the development/maintenance of the nervous & immune system & role in stress management
* Critical work contributed to our understanding of the role of nerve growth factor in cancers, tumours and the brain in health & disease
Rosalind Franklin
* Co-discovered the double-helix structure of DNA, forming basis for modern biotechnology
* Franklin obtained images of DNA using x-ray crystallography, an idea defined by Wilkins
* Watson & Crick used images and available evidence to theorise the nucleotide base scaffold and how genetic information is transferred in living material
Rita Levi-Montalcini (1909-2012)
* Discovered and characterised nerve growth factor
* Identified its importance in the development/maintenance of the nervous & immune system & role in stress management
* Critical work contributed to our understanding of the role of nerve growth factor in cancers, tumours and the brain in health & disease
Rosalind Franklin (1920-1958), Maurice Wilkins (1916-2004), James Watson (1928-) & Francis Crick (1916-2014)
* Co-discovered the double-helix structure of DNA, forming basis for modern biotechnology
* Franklin obtained images of DNA using x-ray crystallography, an idea defined by Wilkins
* Watson & Crick used images and available evidence to theorise the nucleotide base scaffold and how genetic information is transferred in living material
Foundations of genetic expression
Basis of molecular biology
Genotype
* The “Genetic blueprint”
* ….. chromosomes pairs inherited from parents
* Genes are segment of DNA with a specific code sequence
* The genome is an individual’s entire genetic sequence containing the full set of …..
Phenotype
* Observation characteristics resulting from the ….. of the genotype
* Also dependent on ….. and …..
23
Genes
Expression
Behaviours & environment
What is DNA?
DNA structure
* Double helix phosphate-sugar backbone bound by base pairs – the nucleotide
- Adenine = Thymine
- Cytosine = Guanine
What is RNA? How do the base pairs differ to DNA?
- RNA is a single stranded nucleic acid used in replication and protein synthesis
- Adenine = uracil
- Cytosine = Guanine
What are codons?
Genetic alphabet
* The letters along DNA/RNA strands are deciphered in triplets known as codons
* A codon “codes” for one of the 20 amino acids
* Amino acids are the building blocks of life, stringing together to form proteins
EG CCG = arginine
What is protein synthesis? What are the two phases involved?
Protein synthesis
* Two major phases in gene expression and protein synthesis:
- 1. Transcription: creation of complimentary strand of RNA based on DNA template
- 2. Translation – protein synthesis from amino acid chains determined by base sequences transcribed to RNA
How are genes relevant to health and human performance?
Health
* Disease prevention
* Healthy aging
* Injury treatment
* Exercise effects
* Diet effects
* Many more….
Human performance
* Predicting performance (Talent ID)
* Athlete trainability
* Doping/performance-enhancing drugs
For your health – Understanding & fighting cancer
- Molecular biologists have identified the epi-genetic effects of several behavioural, environmental and chemical stressors
- ….. gene activity helps stop the formation of tumours – ….. activity of this gene increases predisposition to cancer
- These discoveries aid in the development of …. and ….. measures
P53
Inhibited
Cures & preventative
Exercise & protein synthesis - myofibrillar
In untrained, myofibrillar fractional synthetic rate increase is stimulus specific.
Trained & untrained individuals have greater myofibrillar FSR at rest and unspecific response to exercise stimulus.
Intracellular signalling mediates the exercise-induced response to resistance and endurance training, leading to specific protein synthesis
In untrained, mitochondrial FSR increase is non-specific to exercise stimulus. Trained individuals have specific mitochondrial FSR response to stimulus - endurance, not resistance exercise.
7.04 – Genetics & athletic potential
Identifying athletic potential – gene expression
Angiotensin converting enzyme (ACE)
* Central component of the ……-…… ….. ….. (RAAS), which controls blood pressure by ….. …… in the body
* Converts ang I to angiotension II – a powerful ……
* Insertion variant more prevalent in ….. athletes – lower ….. levels, permitting higher maximal heart rate and oxygen consumption
* Deletion variation & ACE greater in power athletes
- Renin-angiotensin aldosterone system
- Fluid registration
- vasoconstrictor
- Endurance
- ACE
7.04 – Genetics & athletic potential
- …… is the primary mediator of the RAAS synthesised in the liver and cleaved by renin to yield ANG-I, which ACE catalyses to ANG-II
- …. is the rate-limiting steps to ANG-II production
- The …. allele of the M235T polymorphic site has been correlated with ….. ANG-II levels and therefore increased …. and ….. growth
- …. allele is more prevalent in endurance athletes
Angiotensinogen AGT
Renin
C allele
Greater
BP & muscle growth
T
7.04 – Genetics & athletic potential
- …… responsible for synthesising the alpha protein which stabilises actin filaments in ….-twitch muscle fibre Z-lines
- Prevalence of this gene more prevalent in power athletes, with >…..% having atleast one ….. allele
- ~…..% of the population does not have ACTN3 and may have fewer IIa/x fibres, develop less strength and power and be more susceptible to muscle damage
Actinin-3 (ACTN3)
Fast-twitch
>90%
R
~20%
7.04 – Genetics & athletic potential
- PGC1a is a critical ….. factor protein that is the master metabolic regulator, unregulated by exercise
- Regulates …. ……, …. …. ….. and B oxidation, gluconeogenesis, brown adipose thermogenesis, …… and fibre type adaptations
Transcription
Mitochondrial biogenesis
Fatty acid mobilisation
Angiogenesis
7.04 – Genetics & athletic potential
- ……. protein synthesis stimulates …… and …… – the formation and adaptation of blood vessels
- Expression signalled by ……
- HIF1 master regulator of cellular and systemic homeostatic response to …..
- Critical protein in ….. adaptations
Vascular endothelial growth factor (VEGF)
PGC1a and hypoxia inducible factor 1 (HIF1) after ischemia
Hypoxia
Endurance