EB12 part 2

Question 1

What does Tajimas D(ifferences) do

Answer 1

tests for imbalances in polymorphism frequencies in the data set

Question 2

what does pi equal under the standard neutral model

Answer 2

pi = thetaw = 4Neu

Question 3

what do significant differences between pi and thetaw indicate

Answer 3

deviation from SNM due to

demography: i.e. population not in equilibrium or subdivided (not panmitic or not neutral)

Question 4

what is tajimas D

Answer 4

(pi-thetaw)/sd

sd = standard deviation

Question 5

what is tajimas d simialr to and why

Answer 5

simialr to t test as differences greater than sd are unlikely under the null hypothesis

Question 6

what contributes more to pi common or rare variants.

Answer 6

common variants contribute more than rare variants to measures of pairwise differences like pi

Question 7

how do rare variants contribute to thetaw compared to pi

Answer 7

thetaw is based on counting the no. of polymorphic sites, regardless frequency of alelles, so an excess of rare alleles will greatly inflate thetaq while contributing little to pi
thetaw > pi

Question 8

what does it mean if Tajimas D is negative

Answer 8

there is an excess of rare variants indicating purifying selection against them, probably due to purifying selection

Question 9

what does it mean if tajimas D is positive

Answer 9

theres an excess of common variants, i.e. excess of sites with high frequencies of alleles indicating balancing selection, maintaining diversity.

Question 10

what is TLR4

Answer 10

toll like receptor gene involved in immune response

Question 11

what doe tajimas d for TLR4 show

Answer 11

TD: significantly negative for NS sites in TLR4: suggests purifying selection, keeping varaints at these sites at low frequencies suggesting could be deleterious
TD: non significant for non coding sites.

Question 12

what were sites with purifying selection in TLR4 later shown to be associated with

Answer 12

meningococcal ingections with mutations in these sights leading to an increased susceptibility to infection

Question 13

what is a selective sweep

Answer 13

strong selection at one site will result in loss of variation in neighbouring sites despite neutrality as neighbours carried by linkage

Question 14

what might lack of variation (heterozygosity) in a long stretch of DNA indicate

Answer 14

positive selection for an advantageous allele within that region
or purifying selection against deleterious alleles

Question 15

Give an example of a selective sweep in drosophila

Answer 15

two regions of D. melanogaster X chromosome show less variability in non-African compared to African populations.
this indicates fixation of adaptive mutations as D. melanogaster spread out of africa

Question 16

give an example of a selective sweep in humans

Answer 16

lactase persistance

part of chromosome containing lactase tolerance gene is highly homozygous over a large area.

Question 17

what can homozygosity tracks associated with lactase persistance tell us

Answer 17

length of this area can be used to infer when the selective sweep occured
the more recent the less time recombination has had to dissociate from the selected locus, so younger the change.

Question 18

how does distribution of lactase persistance vary

Answer 18

decreases from north to souther europe - from high cattle areas to lower

Question 19

what does recombination do

Answer 19

removes or reduces effects due to linkage, therefore prevents loss of genetic diversity

Question 20

under neutral model what should rate of divergence and rare of polymorphism be

Answer 20

under neutral polymorphisms (both silent and non silent) are fixed at equal rates and therefore the ratio of divergences should be equal to the ratio of polymorphisms
dN/dS = pN/pS
(dN/dS)/(pN/pS )= 1

Question 21

what does (dN/dS)/(pN/pS) < 1 show

Answer 21

slower fixation of AA changing alleles indicating purifying selection

Question 22

what does (dN/dS)/(pN/pS) > 1 show

Answer 22

faster fixation of AA changing alleles compared to expectation indicating postiive selection

Question 23

what is the Mcdonald Kreitman test

Answer 23

a simple test for deviations from neutrality

Question 24

what are the varaibles in the mcdonald kreitman test

Answer 24

X: fixed non synonymous
Y: fixed synonymous
Z: polymorphic (p) non synonymous
U: polymorphic (u) non synonymous

Question 25

what is the null hypothesis of the mcdonald krietman test

Answer 25

ratio of nonsynonymous to synonymous variation within a species is equal to the ratio of nonsynonymous to synonymous varaition between species

Question 26

what is expected in the mkt under positive selection

Answer 26

an excess of x

fixed non synonymous

Question 27

what is equation for mkt

Answer 27

x/y = z/u
DN/DS = PN/PS
where DN/DS if for total whereas dN/dS is for per site

Question 28

what doe DN = (DS*(PN/PS) give

Answer 28

the excess of deficiency of non synonymous changes due to selection

Question 29

give an example of mkt

Answer 29

in drosophila
total no. of non synonymous divergence (DN) = 7
total no. of synonymous divergence (DS) = 17
total no. of polymorphic nonsynonymous divergence (PN) =2
total no. of polymorphic nonsynmous divergence (PS) = 42
therefore
7-(17*2/42) = 6.32
this shows that there are 6.32 AA changes in ADH due to positive selection