Lecture 3

Question 1

Lambda = rate of amino acid change.

Answer 1

= substitutions per amino acid site per unit time
= (total substitutions/length of protein)/total time
lambda = k/2T

Question 2

Observed divergence (D) will underestimate the number of changes that have actually happened if there are multiple hits and parallel changes:
(2)

Answer 2

• K = -In(1-D)

- This is the formula to correct for multiple hits

Question 3

What assumptions do we make in order to correct for multiple hits?

Answer 3

• We assume all amino acid replacements happen with equal likelihood

Question 4

The likelihood of amino acids changes depends on:

3

Answer 4

• The pattern of DNA mutation
• The genetic code (four fold degenerate sites etc)
• Functional equivalency of amino acids, size and polarity

Question 5

Dayhoff matrices:

Answer 5

• The likelihood of each type of amino acid replacements being derived empirically from data of closely related sequences

Question 6

How do you check that rates are constant over time?

4 points

Answer 6

1. Align multiple sequences
2. Calculate D for each pair of sequences
3. Estimate K to correct for multiple substitutions
4. Estimate T from the fossil records

Question 7

Different proteins have different substitution rates, why?

Answer 7

• Different proteins have different functional constraints

Question 8

Kimura and Ohta concluded that..

2

Answer 8

• different proteins evolve at different rates because they have different proportions of deleterious mutations
• each protein keeps to its own clock

Question 9

If most substitutions in proteins are neutral:

Answer 9

k = 2Nu X (1/2N) = u

Question 10

If most substitutions in proteins are adaptive:

Answer 10

k = 4Nuas
It is unlikely that the product of population size, advantageous mutation rate and selective co-efficient would be constant over the phylogeny of species

Question 11

Do all proteins evolve in a clock like way?

2

Answer 11

• No!

- When they don’t this might be telling us something

Question 12

If the clock holds then we expect Dax = Dbx.

Answer 12

• Look at sites that are different and attribute where they most likely happened (because its the most parsimonious scenario) when two species are compared to an out group species

Question 13

What values would lead to rejection of the null hypothesis, that there is a clock?

Answer 13

When a chi squared is greater than the threshold:

- Both are greater than the 3.84 threshold and are therefore significant at p<0.05

Question 14

Drosophila Esterase 6 in D.melanogaster.

2

Answer 14

• In D.mel the transfer of Est6 induces females to lay rather than re-mate.
• It is a monomer. In other species it is a dimer, and isn’t found in the ejaculatory duct.

Question 15

Relaxation of selective restraint:

3

Answer 15

• less deleterious mutations
• more neutral mutations
• increase rate of change

Question 16

Selection for amino acid change in some lineages:

Answer 16

• new amino acids arise that are favourable

Question 17

The “primate slow down”:

Answer 17

• A difference in the molecular level of evolution.

Question 18

Mutational input can be in the form of:

4

Answer 18

• DNA damage (exogenous, endogenous)
• Replication errors (base misincorporations, slippage)
• DNA repaire (enzyme efficiency)
• Selection (standing variation, rates of evolution)

Question 19

Generation time hypothesis:

Answer 19

• More replications per year are expected to lead to more errors per year.

Question 20

Metabolic rate hypothesis:

Answer 20

• The higher the metabolic rate, the more DNA damaging free radicals

Question 21

DNA repair hypothesis:

2

Answer 21

• Large animals have more cells and longer life span, so error checking will be selected to be better (the primate slow down).
• Big species will evolve at a slower rate on the nuclear level than smaller species.

Question 22

Ohta’s nearly neutral model:

3

Answer 22

• population size is relevant to fixation rate.
• Slightly deleterious alleles will occasionally get fixed.
• They are more likely to become fixed in large population sizes.