W4L1 Molecular Population Genetics and more tests of Neutrality M

Question 1

What is the advantage of neutral theory

Answer 1

it gives us expectations about molecular evolution in the absence of selection

Question 2

Way of identifying changes in nucleotide

Answer 2

-Measure every polymorphic site
-measure minor allele frequency and count total amount of singleton via frequency spectrum

Question 3

Measuring nucleotide diversity

Answer 3

-create a table which compare the amount of difference between each alleales polymorphic site
-create a average pi

Question 4

Descriptive metric unit

Answer 4

• S (the number of segregating sites)
• p (the frequency of a variant)
• MAF (minor allele frequency)
• Haplotypes ( a particular combination)
• p (average pairwise divergence)
• Hobs (the frequency of heterozygotes)

Question 5

Some theoretical metrics to give expectation

Answer 5

• Ne : The effective population size
• Hexp : the expected number of heterozygotes
• 0: ‘theta’. The expected nucleotide diversity and we expect theta=pi

Question 6

Calculating theta by waterson

Answer 6

Waterson (1975) found that q = 4Neµ and it can be calculated from S.

Question 7

Calculating theta under the neutral model

Answer 7

Question 8

Tajimas D test

Answer 8

compares q (neutral expectation) to p (observed) to address frequency spectrum deviations
Tajimas D = p- q/
Sqr Var(p- q)
-if the value is negative, there is an excess of rare singelton
-if the value is positive, there is a lack of rare singleton

Question 9

What would the reason be for the deviation between pi and theta

Answer 9

-population size does not stay the constant

Question 10

coalescence

Answer 10

Looking back in time the lineages of all contemporary alleles will eventually “coalesce” to a single ancestor
There are n-1 event coalescence per sample size of n
On average, it will take 2Ne Generations to go from a large sample down to two lineages and the total for coalescent is 4Ne

Question 11

The effect of a bottleneck on the coalescent

Answer 11

• a positive tajimaD, fewer mutation than expected if there is a recent bottleneck
  -negative tajimaD, more mutation than expected if the bottleneck event is long ago

Question 12

Coalescence with expanding population size

Answer 12

-a negative TajimaD result can indicate a population boom

Question 13

What can TajimaD tell

Answer 13

-if there is a size fluctuation in the past

Question 14

TajimaD and cotton bollworm

Answer 14

Genomic study of 141 individuals of cotton bollworm, which were collected from 13 locations in three cotton-producing regions of China, namely the Yellow River Region (YRR), the Changjiang River Region (CRR) and the Northwestern Region (NR)
* 5,227,071 high-quality SNPs
* Mean Tajima’s D values of different populations ranged from −1.22 to −0.67 show that there is a population expansion recently

Question 15

Linkage Disequilibrium

Answer 15

the non-random association of alleles at different loci in a population

Question 16

What is a haplotype

Answer 16

is one combination of allelic states that is inherited together

Question 17

How is haplotype created

Answer 17

-at first, there is 3 linked sites, after a few generation, drift may bring the new mutant-bearing allele to higher frequency, creating linkage disequilibrium in preexisting polymorphism. But it can be erode by recombination overtime

Question 18

Loss of haplotype overtime

Answer 18

Let’s call the recombination rate between two polymorphisms c
The probability that the haplotype is NOT broken down in one generation
P=1-c
The probability the haplotype is not broken down in G generations is:
P=(1-c)^G

Question 19

Homosapien and Neanderthal cross breeding

Answer 19

Admixture: the mixing of two genetically differentiated population
Initial Linkage dismorphia will be porpotional to alleles frequency differences between the two population and is unrelated to the distance between the markers
Extended LD: dependent on migration rate and recombination rate

Question 20

Factors affecting LD

Answer 20

Mutation, drift, limited recombination
Demographic effects –Admixture
–Bottlenecks eg. Founder effects
Selective sweeps

Question 21

Selective sweep and LD

Answer 21

Left in the patterns of nucleotide polymorphism
* Locally reduced variation
* Skewed frequency spectrum negative TajimaD
* Increased LD/haplotypes

Question 22

FOXP2 selective sweep example

Answer 22

• mutations associated with severe articulation problems, linguistic and grammatical impairment
  -it is a regulator for a lot of gene
  -only 2 amino acid between mouse and chimp but 2 difference between human and chimp
  -but it turned out that the result is due to sampling bias