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3s1: Evolution of health and disease > Week 1 > Flashcards

Week 1 Flashcards

1
Q

How does evolution shape diseases?

A

Bodies not machines, shaped by evolutionary processes
Compromises and examples of ‘bad design’

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2
Q

How does natural selection resource usage result in disease?

A

Natural selection uses raw material available and maximises ‘fitness’ (not health / lifespan)
E.g. selection for traits that increase reproductive success (fitness), but increase susceptibility to disease (trade offs)

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3
Q

How does culture impact health?

A

Evolution slower than cultural change
E.g. diets v lifestyles, leading to mismatch

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4
Q

How does pathogens impact species health?

A

Pathogens evolve faster than hosts
Rapid pathogen evolution

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5
Q

What are examples of bad evolutionary designs?

A

Eye
Path of the male urethra & vas deferens
Double curvature of the spine
Impacted wisdom teeth
Giraffe pharangeal nerve

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6
Q

Why is the design of the mammalian eye bad?

A

The vertebrate retina is inverted in the sense that the light-sensing cells are in the back of the retina,
Light has to pass through layers of neurons and capillaries before it reaches the photosensitive sections of the rods and cones

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7
Q

What are the problems with Giraffe pharangeal nerve?

A

Early fish design made pharengel nerve loop through the dorsal aorta
So in giraffe this is the same, resulting in the nerve being 5m long
Longer the nerve slower the transmission

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8
Q

What is the history of the ureto-genital system?

A

Urethra passes through the prostate gland
Prostate prone to infection and commonly blocks urethra
Vas deferens also passes up and over the ureter - relic of ancestral condition where testes held within body cavity

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9
Q

What are the three potential causes of the evolution of lactose tolerance?

A

Adaptation in response to pastoralism (keeping and milking cattle / camels)
Solar radiation
Aridity

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10
Q

What was the methods used to deduce the origin of lactose tolerance?

A

Phylogenetic comparative methods used in a cross cultural study to distinguish these alternatives

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11
Q

What needs to be accounted for phylogeny?

A

Phylogenetic pseudoreplication (1 adaptation may cause number of species to live in difference areas rather than multiple independant)

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12
Q

What is believed to be the cause lactose tolerance?

A

Lactase persistence correlated with pastoralism, not aridity or solar radiation

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13
Q

What is the most likely relationship for the origin of lactose tolerance?

A

Populations without lactose persistence started to keep and milk cattle resulting later lactase production

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14
Q

How did Evershed challenge the nature of lactase persistence?

A

Studied detailed distributions of milk exploitation across Europe over the past 9,000 years
Found only weak associations of LP genotype with history of milk consumption
Other reasons for the beneficial effects of LP should be considered

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15
Q

What is the genetic basis for the lactase persistence?

A

Lactase persistence stays high in intestinal cells
Upstream changes to LCT gene - regulatory changes
Persistence alleles bind transcription factors strongly

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16
Q

What is the haplotype network for lactase persistence?

A

European H98 (only cows) and African H100 (cows and camels) alleles have same non lactase persistence ancestor H84 (only camels)
H99 has different background haplotype H107
Differing history of adaptation to milking culture

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17
Q

What is an overview of HIV?

A

HIV is the virus that causes AIDS
Zoonotic origin
Two main groups HIV-1 and HIV-2 (HIV-1N caused epidemic in humans)
Initial clinical description decades ago, millions of deaths.

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18
Q

What is an overview of HIV infection locations?

A

Epicentre in sub-Saharan Africa
Elsewhere, new waves of infection

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19
Q

What is an overview of HIV treatments?

A

Combinatorial antiretroviral treatments afford clinical relief to those who receive it

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20
Q

What is the origin of HIV-1M or N humans?

A

Recombination between 3 different SIV (simian immunodeficiency virus) this infected a chimpanzee
2 spill overs in SIVcpz resulted in transfer into humans and the 2 different strains

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21
Q

What is the origin of HIV-1O or P humans?

A

Recombination between 3 different SIV (simian immunodeficiency virus) this infected a chimpanzee
1 spill over in SIVcpz resulted in transfer into gorrillas
2 spill overs in SIVgor resulted in the 2 different strains jumping into humans

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22
Q

What is an overview of the transfer of primate lentiviruses?

A

A large amount of transfer between viruses, not just between closely related primates but the middle and long distance too

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23
Q

What are the relationship between HIV and SIV?

A

Closest relatives of HIV are SIVs (many tens of distinct lentiviruses, SIVs, that infect primates in Africa)

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24
Q

What is the origin of HIV2 in humans?

A

9 spill over events from Sooty Mangabay

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25
Q

What are the resovoirs of the HIV types?

A

HIV-2 = Sooty Mangabay monkey
HIV-1 = Believed to have been from chimps initially due to closely related lentivirus, later found in gorrilas and then later found in wild chimps

26
Q

How did they detect the natural source of HIV-1?

A

Chimps classified into 4 subspecies, based on mitochondrial DNA
Developed techniques for detecting SIV infection from stool samples
Closest relative of HIV-1 came from P. t troglodytes chimps

27
Q

What is the origin of SIVcpz?

A

SIVcpz (the progenitor of main HIV-1 lineages) arose as a recombinant of ancestral SIV lineages in 2 spp of mangabeys, + 1 unknown SIV
Chimps acquired this recombinant virus by cross species transmission

28
Q

What is an overview on the origin of HIV-1?

A

Each resulted from 4 independent cross species transmissions during the 20th century (M & N Chimps and O & P from Gorilla)

29
Q

What happened to HIV-1M?

A

M type in Cameroon - went south to Congo river and on to Kinshasa – where M group pandemic originated

30
Q

What caused the crossing over of HIV into humans?

A

Transmission through food preparation and meat butchery, exposure to infected primate blood.
Hunting and field dressing of chimps common in W Africa
Further transmission has increased - bush meat markets, increased traffic into previously remote areas

31
Q

What things can increase the exposure for a cross species transmission?

A

Distrubution of reservoir species (>40 African non human species have SIV)
Prevalence in resovoir species (in some species >50%)
Interspecies contanct

32
Q

What can cause spill over for cross species transmission?

A

Interspecies contact (eg hunting)
Dose of exposure (higher viral load the higher risk)
Host species evolutionary divergence

33
Q

What can increase the rate of viral spread?

A

Adaptability (mutation rates, rate of turnover, gene acquisition/loss)
Counteraction of nonpautologous restriction factors (preadaptation due to low species barrier)
Utilisation of non-autologous restriction factors (high adaptability, alternative factor usage)
Intraspecies transmission route (sexual and vertical transmission, needle sharing)

34
Q

Lentiviruses are variable but what do they all have?

A

Structural and enzymatic proteins (gag, pol, and env)
Regulatory proteins (tat and rev)
Accessory genes (vif, vpr, and nef)
HIV-1 and its closest simian counterparts, also (viral protein U (Vpu))

35
Q

What key changes allowd for the transmission of HIV-1M into human host?

A

Los of vpx
Elongation of vif
Loss of env-nef overlap

36
Q

What is evolution?

A

Descent with modification

37
Q

What are the 2 key concepts for evolution?

A

All living things have a single common ancestor
Gradual change over time

38
Q

What are the 2 types to gradual change over time?

A

Across populations - speciation
Within populations - changes in gene frequency

39
Q

What is adaptive evolution?

A

Natural selection

40
Q

What is non adaptive evolution?

A

Genetic drift and bottlenecks

41
Q

What type of evolution explain adaptive complexity?

A

Natural selection

42
Q

What creates genetic diversity for evolution?

A

Mutations, which generates the raw material for evolutions

43
Q

What are the different types of mutations?

A

Single nucleotide mutations (SNPs)
Insertions / deletions
Translocations
Inversions
Gene duplications
Genome duplications (changes to ploidy levels)

44
Q

What are causes of mutations?

A

Copy errors (‘natural’ mistakes) = spontaneous
Radiation
UV
Chemicals
Environmental factors

45
Q

What are the different outcomes for mutations?

A

deleterious (common)
selectively neutral
advantageous (rare)

46
Q

What are the relationship between mutations with fitness?

A

Mutations occur at random with respect to fitness

47
Q

What are the outcomes investigated by SNPs in viruses?

A

40% mutations are lethal
30% mutations are wild type
0.25% mutations are beneficial
The rest are various degrees of deletirious

48
Q

What is the traditional idea of natural selection?

A

Survival of the fittest
Survival of the form that leaves most copies of itself in successive generations

49
Q

Why is survival of the fittest misleading?

A

Survival not always the most important fitness trait

50
Q

What is natural selection?

A

Differential survival of replicator with cumulative selection
Key elements: replicators, error and differential survival

51
Q

What is the most famous example of natural selection?

A

Darwin’s finches - one original species landed on island and differentiated into different species with different break morphologies to best adapted to the environment

52
Q

What is an example geographical natural selection on human traits?

A

Humans with darker skin in areas that are nearer the equator and paler the further away

53
Q

Why does skin colour have a geographical natural selection?

A

Naturally selected in response to:
Protection against Folate damage (low latitudes)
Requirement to synthesise vitamin D (high latitudes)

54
Q

What are the major modes of selection?

A

Stabilising selection
Direction selection
Disruptive selection

55
Q

What is genetic drift?

A

Random inheritance for alleles impacting the frequency they appear in the next generation

56
Q

What is genetic bottleknecking?

A

Drastic population reduction reduce the number of alleles avaliable in a population, potentially wiping out some alleles and inflating proportion of others

57
Q

What is an example of genetic bottleknecking?

A

Global human genetic variation can be explained via genetic drift and bottlenecks in the Out of Africa model
Most human genetic variation is still inside Africa due to only a small number of humans ever leaving

58
Q

How has human genetic bottleknecking effected human health?

A

Locus responsible for Myotonic Dystrophy (MD)
Non-African peoples have higher frequency of MD
MD rare within South African peoples

59
Q

What causes Myotonic dystrophy?

A

Protein kinase (DMPK) –expressed in skeletal muscle
This causes the expansion of CTG repeats
Autosomal dominant inheritance

60
Q

What are the genetics of Myotonic dystrophy?

A

Contains CTG repeats, normally 5-30
Disease caused when repeats >50
non African peoples have higher frequency of MD repeat expansion and MD

61
Q

What is migration and gene flow for health?

A

Relevant to current distribution of (medically relevant) global genetic variation within humans

3s1: Evolution of health and disease (10 decks)

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