L4 & L5 : Molecular Adaptations for Survival Flashcards

1
Q

How can extremophiles be categorised?

A

By specific conditions (eg. thermophile)
Extreme environments may pose combined challenges (eg. haloalkaliphiles)
Extremophiles adapt, defend, exploit

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2
Q

What are important functions of the cell membrane and associated challenges?

A

Barrier function to prevent unregulated in/outward transport
Improved impermeability to protons for acidophiles

Fluidity required for lateral movement of proteins
Fluidity of mesophilic membrane increased at high temps and decreased at low temp/high pressure

Modifications of cell surface proteins to support respiration in alkaliphiles

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3
Q

How do archaeal thermophiles decrease membrane fluidity?

A

Archaeal membranes have different kinds of phospholipids within them (ether-linked)

Isoprenoid ether lipids are liquid crystalline and provide low permeability from 1-100 deg
Tetraether-linked lipids increase rigidity and can span entire membrane

Nature of the chain is regulated over temperature changes and has lower permeability due to less space between phospholipids

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4
Q

How does piezophilic Colwellia increase membrane fluidity

A

Different membrane composition so more fluid to maintain function under high pressure

More polyunsaturated FAs in phospholipids
Express delta-9-acyl phospholipid desaturase
No cis to trans isoemrases
Metabolism adapted to create required fatty acids

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5
Q

How does S. acidocaldarius lower proton permeability?

A

Thermophilic acidophile
Liposomes prepared from lipid fractions of S. acid show distinctive low proton permeability at different temperatures

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6
Q

How do acidophiles maintain membrane potential?

A

Mesophile typically have ~-73 mV
Proton gradient used by secondary transporters etc

May degrade weak acid uncouplers to prevent disruption of pH balance
Actively pump in K+ to maintain positive intracellular environment against high external proton conc

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7
Q

How do alkaliphiles use proton gradients as source of energy?

A

Rely on proton-motive force for ATP synthesis

Use ATP synthase to import proteins and maintain neutral internal pH
- Mutations give adaptations that allow enhanced ability to bind H+ at high pH
- Modified so ATPase activity absent and cannot release H+ extracellularly
Create localised lowered extracellular pH
- Make and secrete acids produced through fermentation
- Produce acidic, negative components for cellular surface

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8
Q

Examples of protein adaptations in extremophiles?

A

Structures and general characteristics may be adapted to maintain structure
Eg. denser core and tighter packing in high pressure environment
Surface of proteins may be altered to cope with altered internal conditions
Different chaperones for different conditions

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9
Q

How are psychrophile enzymes adapted?

A

Low temps mean less energy available
More flexible active sites with decreased substrate affinity
Also results in decreased specificity for substrates

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10
Q

Examples of opportunities that can be exploited?

A

In acidic conditioons:
Fe2+ more stable and oxidises less quickly to Fe3+
Acidophiles able to use Fe2+ oxidation as energy source

At low temps:
O2 more soluble
Psychrophles increase expression of aerobic metabolism enzymes
Acyl desaturases can use O2 as substrate in desaturation of FAs (flexible membranes)

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11
Q

What is the risk of low temps and increased O2 solubility?

A

Increased ROS and oxidative stress

Decreased levels of oxidisable AAs in proteins
Deletion of ROS-producing pathways
Increased synthesis of glutathione synthetase and superoxide dismutase

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12
Q

How can extremophiles be studied through cultivation?

A

~1% of bacteria in samples are cultivatable
Can attempt to recreate conditions or grow extremotolerants
Microbes may require growth factors provided by others
Optimal conditions can still result in slow growth
Material needed for DNA/mRNA analysis

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13
Q

How can extremophiles be studied using bioinformatics?

A

Phyla can be classified on basis of 16S rRNA genes
High throughput sequencing allows bioinformatic analysis, predict gene function based on homology, infer metabolic pathways
Large proportion of genes may have no predicted function

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14
Q

Challenges of adapting to environments?

A

Evolution suited to particular habitat with limited variation
Acute changes require immediate response - may not be sustainable
Chronic changes may induce alternative responses - may not be suitable

Adaptation may therefor alter sensory strategies and resulting responses

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15
Q

Why is oxygen important?

A

Terminal electron acceptor of aerobic respiration
Complex IV (cytochrome oxidase) of ETC reduces oxygen

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16
Q

Examples of hypoxic environments?

A

At seas level: 21% O2, 0.03% CO2

Higher altitude = decreased pressure and lower concs
Underground = 7.2% O2, 6% CO2 (lower ratio)
Diving mammals = up to 2h, anaerobic (adaptations affected by anticipated length of dive)
Frozen lakes = decreased photosynthesis
Eutrophication depletes O2

17
Q

What are some general responses to hypobaric hypoxia?

A

Reduce need for oxygen
- decrease metabolic rate and switch to anaerobic metabolism
Improve delivery of oxygen
- changes to cardiovascular and respiratory system
Modify oxygen-sensing machines

18
Q

What does acute response entail?

A

Immediate
Largely though nervous system

19
Q

What does chronic response entail?

A

Acclimatisation, mitigates issues caused by immediate response
Changes in gene expression, altering behaviour and number of cells

20
Q

What does adaptation entail?

A

Improve survivability (including next gen)
Changes in allele frequency
- Spontaneous mutations/admixture
Strategies differ between populations

21
Q

Examples of established high altitude human populations?

A

Tibetan plateau - largest, most studied
Andean - most recent, seem less well-adapted
Ethiopian highlands - longest, least studied
Studies typically compare genetics with local sea-level populations

22
Q

How is respiratory rate controlled by ventilatory drive?

A

Typically controlled by CO2 levels and pH sensing
Central chemoreceptors in brain stem stimulate hyperventilation at low pH (acidosis)
Alkalosis depresses ventilation
Kidneys may also regulate pH through production of bicarbonate

23
Q

What is the acute hypoxic ventilatory response?

A

Carotid bodies detect decreased O2 - signals to nervous system, leading to hyperventilation
Pulmonary SMCs detect decreased O2 - cause constriction of vessel for ventilation-perfusion matching

24
Q

What does hypoxic ventilatory response lead to?

A

Decreased CO2 and respiratory alkalosis
Kidneys mitigate through increased production of bicarbonate ions
Acute response to hypobaric hypoxia disrupted by regulatory response to hypercapnia (central chemoreceptors send stronger signals)

25
How does acclimatisation to hypoxia occur?
Ventilatory - Increased sensitivity of carotid bodies - Sustained increase in breathing Improved oxygen delivery - Angiogenesis (growth of blood vessels) - Increased no. RBCs Metabolic changes - Increased glycolytsis - Decreased aerobic pathways - Protection against oxidative stress
26
How does HIF oxygen sensing system work in very low O2?
HIFa likely to reach nucleus in functional state Interacts with proteins in complex and binds to hypoxia response elements (HRE), Strongly stimulates transcription of genes that assist in coping with low O2 levels (carotid body sensitivity, increases synthesis RBCs)
27
How does HIF oxygen sensing system work in normoxia?
PHD (proline hydroxylase domain): Uses O2 as substrate and hydroxylates HIFa, allowing VHL to ubiquitinate HIFa -> degradation FIH1 (factor inhibiting HIFa): Uses O2 as substrate and also hydroxylates HIFa but at different position HIFa may enter nucleus but cannot interact HIFa continuously expressed and mostly degraded Remaining protein cannot stimulate transcription
28
How does HIF oxygen sensing system work in low O2?
Due to relatively high Km of PHD, small decreases in O2 increase HIFa stability Low Km of FIH1 Some HIFa able to stimulate transcription but response decreased
29
What are 2 examples of conditions caused by poor acclimatisation?
Chronic mountain sickness - erythrocytosis, sleep disturbance (periodic breathing), cyanosis, inc stroke risk Pulmonary hypertension - persistent vasoconstriction, decreased diameter/elasticity, disrupts O2 transport, right ventricular failure Similar symptoms, different causes
30
What are the causes of CMS and PH?
Genetic variability in susceptibility Seen in long-term high altitude sojouners, less in indigenous Less ventilatory acclimatisation to hypoxia, increased activity of other hypoxic responses - chronic pulmonary vasoconstriction -> remodelling - chronic increases in erythrocyte formation -> viscosity of blood
31
What are some evolutionary adaptations to high altitude?
Various mammals show range of adaptations involving sustainable, helpful responses to hypobaric hypoxia Also must deal with cold + greater UV exposure Indigenous - Maintain consistent hyperventilation - Increased levels of lactate - Typically don't have increased conc of RBCs
32
What adaptations to the HIF system are there?
High alt mammals often show loss of function of HIF systems Mutations often blunt some responses to hypoxia
33
What mutations of PHD can occur?
Experimental loss of access at: Translation showed increased erythrocytosis Folding showed increased hypoxic ventilatory response D4E/C127S Tibetan allele has increased affinity for O2 and decreased binding to p23
34
Why is decreased sensitivity to hypoxia advantageous?
In context to metabolic adaptations to hypoxia - Altered hameoglobin affinity - Increased capillary density - Smaller RBCs