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Flashcards in Lecture 3 Deck (22)
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1
Q

Lambda = rate of amino acid change.

A

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

2
Q
Observed divergence (D) will underestimate the number of changes that have actually happened if there are multiple hits and parallel changes:
(2)
A
  • K = -In(1-D)

- This is the formula to correct for multiple hits

3
Q

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

A
  • We assume all amino acid replacements happen with equal likelihood
4
Q

The likelihood of amino acids changes depends on:

3

A
  • The pattern of DNA mutation
  • The genetic code (four fold degenerate sites etc)
  • Functional equivalency of amino acids, size and polarity
5
Q

Dayhoff matrices:

A
  • The likelihood of each type of amino acid replacements being derived empirically from data of closely related sequences
6
Q

How do you check that rates are constant over time?

4 points

A
  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
7
Q

Different proteins have different substitution rates, why?

A
  • Different proteins have different functional constraints
8
Q

Kimura and Ohta concluded that..

2

A
  • different proteins evolve at different rates because they have different proportions of deleterious mutations
  • each protein keeps to its own clock
9
Q

If most substitutions in proteins are neutral:

A

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

10
Q

If most substitutions in proteins are adaptive:

A

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

11
Q

Do all proteins evolve in a clock like way?

2

A
  • No!

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

12
Q

If the clock holds then we expect Dax = Dbx.

A
  • 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
13
Q

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

A

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

14
Q

Drosophila Esterase 6 in D.melanogaster.

2

A
  • 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.
15
Q

Relaxation of selective restraint:

3

A
  • less deleterious mutations
  • more neutral mutations
  • increase rate of change
16
Q

Selection for amino acid change in some lineages:

A
  • new amino acids arise that are favourable
17
Q

The “primate slow down”:

A
  • A difference in the molecular level of evolution.
18
Q

Mutational input can be in the form of:

4

A
  • DNA damage (exogenous, endogenous)
  • Replication errors (base misincorporations, slippage)
  • DNA repaire (enzyme efficiency)
  • Selection (standing variation, rates of evolution)
19
Q

Generation time hypothesis:

A
  • More replications per year are expected to lead to more errors per year.
20
Q

Metabolic rate hypothesis:

A
  • The higher the metabolic rate, the more DNA damaging free radicals
21
Q

DNA repair hypothesis:

2

A
  • 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.
22
Q

Ohta’s nearly neutral model:

3

A
  • 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.