Quiz 3 (Lecture 10)

Question 1

Diseases have both ____ and ____ explanations

Answer 1

mechanistic and evolutionary

Question 2

The mechanistic explanation of Crohns

Answer 2

mutations in NOD (Nucleotide-binding Oligomerization Domamaine) receptors
GWAS studies of NOD mutants
- homo 17 fold greater risk of Crohns
- hetero 2.5 fold greater risk

Question 3

The evolutionary explanation of Crohns

Answer 3

there is an environmental interaction: the severity of Crohn’s disease depends on the state of the microbiome

Question 4

Diseases can be placed into categories:

Answer 4

infectious- caused by pathogens
genetic- caused by genetic defects
degenerative- caused by the vulnerabilities of aging

Question 5

Genetic Defects

Answer 5

are relatively rare, mutational catastrophes (trisomy 18-infants die shortly after birth)

Question 6

Genetic Predispositions

Answer 6

are often polygenic and result from environmental mismatches- neutral or beneficial in some settings, detrimental in others
– genes interact together and with the environment causing disease
- some parts of our genome are most or less susceptible to disease
- more common

Question 7

Catastrophes

Answer 7

include attacks by predators and parasites and accidents
- no variation, either has it or you do not
ex. contracting ebola or rabies

Question 8

Accumulative effects

Answer 8

include smoking and lack of exercise
ex. the impact of lifestyle choices on the risk of heart disease, cancer, and type 2 diabetes

Question 9

Catastrophe example

Answer 9

children born by c-section increased 20% risk of asthma

delivery of birth affects the microbiome and through its interactions with the immune system the risk of allergies, asthma, obesity, and autoimmune diseases

Question 10

The gut is the largest

Answer 10

immune organ

Question 11

The development of gut-associated lymphoid tissue is

Answer 11

triggered by signals produced by gut bacteria
*mammal genome has outsourced this essential function

Question 12

Accumulative effects example

Answer 12

• the likelihood of suffering from peripheral artery disease increases as the exposure to secondhand smoke increases (measured as # of hours exposure per week)
• exposure to secondhand smoke varies across racial groups, ages, and socioeconomic status

Question 13

Disease

Answer 13

a state that decreases survivability, increasing mortality

Question 14

diseases have different causations

Answer 14

genetic interactions with environmental factors (GxE causations)

Question 15

When a cause of the disease is an interaction, both

Answer 15

environmental and genotype factors must be accounted for.
ex. the environmental risks of cancer, such as tobacco and air pollution, depending on genotype

Question 16

Genetic variation in N-acetyl transferase

Answer 16

1) Those with the combination of NAT2 slow acetylator, NAT1 fast acetylator, and current or ever cigarette smoking were 2.7 times more likely to get bladder cancer
2) NAT1 polymorphism interacts with dietary mutagen intake (bbq meat) to increase the risk of pancreatic cancer 2.5 times in men but not in women

Question 17

Organs and tissues vary in their degrees of robustness, resilience, and vulnerability. This mosaic determines…

Answer 17

the spectrum of diseases, both in general and in particular environments

Question 18

Not all organs and tissues are as robust and resilient as possible because of

Answer 18

tradeoffs- producing such structures and processes would cost more than it would pay

Question 19

Tissues with high renewal rates and repair capacities are

Answer 19

relatively tolerant to damage–easily handled
ex. most epithelia

Question 20

Tissues with low renewal rates and repair capacities are

Answer 20

not tolerant of damage–can be lethal
ex. neurons

Question 21

Tissues with high energetic demands

Answer 21

rely exclusively on oxidative metabolism
ex. neurons and heart muscles
- this is why ischemia (lack of O2 and nutrients) rapidly and seriously damage brains, hearts, kidneys, often irreversibly or fatally

Question 22

Tissues with low energetic demands

Answer 22

tolerate hypoxia relatively well because they can switch from oxidative to glycolytic metabolism
ex. adipocytes and fibroblasts

Question 23

Tissues with high energetic demands

Answer 23

rely exclusively on oxidative metabolism
ex. neurons and heart muscles
- this is why ischemia (lack of O2 and nutrients) rapidly and seriously damages brains, hearts, and kidneys, often irreversibly or fatally

Question 24

Protective structures have evolved

Answer 24

to shield vulnerable organs from frequently encountered threats
ex. skull protects brain

Question 25

Some tissues and organs are

Answer 25

immune privileged– they do not permit immune responses that have damaging side effects (like inflammation)
ex. of organs: brain, eyes, gonads
- the price such tissues pay for avoiding the costs of inflammation is vulnerability to pathogens that gain access to them

Question 26

Many structures are vulnerable because

Answer 26

of compromises imposed by tradeoffs
- Synovial joints (wrist, elbow, finger, shoulder, knee) have superior mobility but are vulnerable to arthritis
- Alveolar sacs have excellent gas exchange but are vulnerable to pneumonia when filled with inflammatory exudate

Question 27

Constraints is that

Answer 27

other structures are vulnerable because of historical limitations which prevent further evolution and result in seemingly suboptimal structures

Question 28

Choking

Answer 28

• an example of a constraint
• have a suboptimal design of throat because lungs evolved off of the esophagus

Question 29

Pathologies can then result for two reasons

Answer 29

1) the mechanisms controlling the balance of the tradeoff are perturbed
2) the environment changes

Question 30

1) the mechanisms controlling the balance of the tradeoff are perturbed examples

Answer 30

• the immune defense against infection brings with it the high cost of immunopathology and the risks of autoimmune disease
• the clotting system carries the risk of embolism and stroke

Question 31

2) the environment changes examples

Answer 31

• if the environment changes, costs may exceed benefits until evolution catches up (can take a while)
• modern hygienic environments are abnormal: they elicit pathological immune responses (like asthma and allergies)

Question 32

Some developmental and physiological processes are insensitive

Answer 32

to environmental change
ex. DNA replication
- robust to dysregulation but remain vulnerable to genetic defects

Question 33

Some developmental and physiological processes are very

Answer 33

sensitive to environmental change
ex. glucose metabolism and blood pressure
- have flexibility at cost of vulnerability to dysregulation

Question 34

Sensitive reactions evolve to be

Answer 34

adjustable

Question 35

insensitive reactions evolve to be

Answer 35

fixed

Question 36

Core biological processes are

Answer 36

fixed
ex. DNA replication, transcription of actin for the cytoskeleton
- major features of the body plan are fixed in developmental control (# of head, legs, arms, digits, eyes)

Question 37

adjustable processes example

Answer 37

Glucose distribution is controlled by insulin
- insulin promotes the absorption of glucose from the blood to skeletal muscles and fat tissues by causing fat to be stored rather than used for energy
diseases of homeostasis: insulin resistance and type 2 diabetes