Lecture 7- Coalescent theory Flashcards

1
Q

what does coalescent theory refer to

A

the modelling of how alleles may have been derived from a common ancestor

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2
Q

limitations of this method

A

can only be used when positive selection is weak- assumption that all alleles are equally likely to be passed on

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3
Q

application

A

anthropology, epidemiology, association mapping (variation vs human disease), cancer bio

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4
Q

‘null model’ conditions

A

haploid population (N)
no strong selection
generations are non-overlapping
population size is constant

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5
Q

wright-fisher model

A

model of genetic drift

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6
Q

how does the wright-fisher model work (roughly)

A

traces the mutation through- e.g. looking at the probability it will become fixed/going extinct, can be used from the past or from the present to trace ancestry

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7
Q

what is a coalescent event

A

a point where there is shared ancestry

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8
Q

equation for probability of coalescence

A

(1/N) * i(i-1)/2
i = no of sampled lineages
represents probability that 2 lineages share a parent * number of possible pairs of sampled lineages
i(i-1)/2N

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9
Q

how can you work out time to MRCA from N and i

A

(2N(i-1))/i generations

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10
Q

how do you account for time

A

to look at r at a specific time, plug in the population size at the time r(t)=(i(i-1))/2N(t)

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11
Q

relationship of coalescent events and pop size

A

smaller pop = more events

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12
Q

sequence diversity relationship to mutation rate

A

sequence diversity = 2N*mutation rate

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13
Q

how does pop size impact sequence diversity

A

larger pop size = higher diversity because more time for mutations to emerge

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14
Q

methods of estimating population sizes from phylogenies

A

Tajima’s D, skyline plots

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15
Q

Tajima’s D

A

measures what kind of mutations are occurring- high/med/low frequency, etc- which can be used to infer the structure of a population, e.g. less low-frequency mutations at bottlenecks

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16
Q

skyline plots

A

look at the mathematical relationship between rate of coalescence and population size to calculate an estimated population size

17
Q

example of a skyline plot being used to infer the history of a population size

A

HIV samples from the 50s compared to those from the 90s- there was already diversity, suggesting decent sized pop by this point

18
Q

how can coalescent theory be used to track migration

A

can look at coalescence events which seem to suggest crossover of populations, can infer relationships between sub populations

19
Q

issues that can arise when studying speciation using coalescent theory

A

can end up with incomplete lineage sorting- coalescence doesn’t match the speciation tree based on gene analysis

20
Q

what are association studies

A

studies which aim to associate human genes with specific diseases, within populations- coalescent theory is useful for interpreting these large-scale datasets