Lecture 8

Question 1

Measures of nucleotide diversity

2

Answer 1

• Tally the number of segregating sites (s)

- Calculate the average pairwise divergence between alleles (pi)

Question 2

Descriptive metrics include:

7

Answer 2

• Describe the DNA sequence in different ways
• S
• P
• MAP
• Haplotypes
• Pi
• H

Question 3

S:

2

Answer 3

• Number of segregating sites

- Can calculate theta from S

Question 4

p:

Answer 4

The frequency of a variant

Question 5

MAP:

Answer 5

Minor allele frequency

Question 6

Haplotypes:

Answer 6

A particular combination

Question 7

Pi:

2

Answer 7

• Average pairwise divergence

- Under the neutral theory we expect pi = theta

Question 8

H:

Answer 8

The frequency of heterozygous

Question 9

Metrics estimated with some uncertainty include..

2

Answer 9

• Meu

- Fst

Question 10

Meu:

Answer 10

Mutation rate

Question 11

Fst:

Answer 11

Population structure

Question 12

Theoretical metrics:

3

Answer 12

• Ne
• Hexp
• Theta

Question 13

Ne:

Answer 13

Effective population size

Question 14

Hexp:

4

Answer 14

• The expected number of heterozygous
• 2pq
• 4Nemeu/1+4Nemeu
• Theta/1+theta

Question 15

Theta:

4

Answer 15

• The expected nucleotide diversity
• 4Nemeu
• Under the neutral theory we expect theta = pi
• Can also calculate theta from S

Question 16

Tajimas D test:

Answer 16

• Compares theta (neutral expectation of molecular diversity) to pi (average pair wise divergence) to address frequency spectrum deviations.

Question 17

Coalescence:

3

Answer 17

• Looking back in time the lineages of all contemporary alleles will eventually coalesce to a single ancestor
• There are n-1 coalescence per sample size of n
• On average, it will take 2Ne generations to go from a large sample down to 2 lineages

Question 18

The effect of bottleneck on the coalescent:

4

Answer 18

• Population goes through the bottleneck and then expands again
• This will give us a coalescence tree with two arms separated by really long branch lengths.
• We will find most mutations occur in the two long arms
• Increased number of intermediate frequency, positive Tajimus D.

Question 19

Positive Tajimus D:

3

Answer 19

• Increased number of intermediate frequency
• Bottleneck is an explanation for positive TD
• Deficit of rare variants

Question 20

Negative Tajimus D:

2

Answer 20

• Excess of rare variants

- Coalescence with expanding population size

Question 21

Do polymorphisms in nearby sites evolve independently?

2

Answer 21

• No! Not always

- Linkage equilibrium is a measure of this

Question 22

Linkage Disequilibrium (LD):
(2)

Answer 22

• Non-random association of alleles at different loci in a population
• Correlation between different sites that can be near each other, or on different chromosomes

Question 23

Haplotype:

2

Answer 23

• One combination of allelic states that is inherited together
• Defined by an arbitrary number of sites

Question 24

How does linkage disequilibrium get established in the first place?
(4)

Answer 24

• Imagine 3 linked sites in a linkage equilibrium (of 8 haplotypes)
• A mutation occurs and increases in frequency by drift or selection
• The LD is maintained
• Recombination erodes LD over time

Question 25

The probability that the haplotype is not broken down in G generations..
(2)

Answer 25

• P=(1-c) to the power of G

- Where c is the recombination rate between two polymorphisms

Question 26

Factors affecting LD include

6

Answer 26

• Mutation
• Drift
• Limited recombination
• Admixture
• Bottlenecks
• Selective sweeps

Question 27

Admixture:

2

Answer 27

• The mixing of two genetically differentiate populations

- LD is established between adjacent sites and different chromosomes

Question 28

Extended LD:

Answer 28

Dependent on migration rate and recombination rate