Molecular evolution Flashcards

1
Q

How to compare AA sequences

A

see number of different AA between two species homologous sequences / tot AA in that sequence

Also can make phylogenetic tree by AA substitutions to see divergent time between species

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Example of comparison of AA sequences

A

Hb alpha chain
human to horse, 18 different sites
human to shark, 79 different sites.
make a matrix

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what did Linus Pauling find?

A

2 time Nobel prize winner
1962 - linear relationship between genomes and time since divergence, estimated from fossil record - molecular clock hypothesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

molecular clock hypothesis

A

rate of evolutionary change of any specified protein was approximately constant over time and over different lineages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what does evolutionary rate equal?

A

rate of nucleotide substitutions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

how to calculate nucleotide substitution rate

A

r=K/2T
no. substitutions per site per year = evolutionary distance between 2 sequences/2x time of divergence between two sequences.

a simple (parsimonious) process is assumed(each nt changed only once)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how to find evolutionary distance?

A

P proportion of NT which have changed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

define synonymous and non synonymous substitution

A

synonymous - a substitution which can give the same AA. likely to occur. possible since some AA are degenerate.
Non synonymous subs are unlikely to occur because they cause a biological change in the organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is the Ka/Ks ratio

A
Ks = synonymous sub rate
Ka = non syn sub rate.
not likely/likely
usually <1
rarely>1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

how do you know if positive selection has occurred

A

Ka/Ks>1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

example of genes positively selected for

A

immune system genes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what does population genetics study

A

change of allele frequencies of population over time

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

who came up with the neutral theory of molecular evolution?

A

motoo kimura 1968

very high rate of NT substitutions must mean that most mutations are neutral in NS, and caused by random drift go alleles that are selectively neutral.
Darwinian - survival of the fittest
Kimurian - survival of the luckiest

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

why may some regions of genes show less substitution than others?

A

functional constraint

eg Hb - c chain shows higher substitution rate than other domains, because it is a non functional region

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what is the opposite of random mating

A

assortative mating

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

examples of genes with high functional constraint

A

Hb

histones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what is an OTU

A

operational taxonomic unit

level of taxonomic separation used

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

how to calculate p distance

what is it

A

Number of mis-matched sites/total no. sites
Simplest estimate of evolutionary distance.
length of branches in an evolutionary tree fits the p distance of OTU pairs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what is multiple substitution

A

when subs occurred multiple times at the same site.

20
Q

how to calculate distance for AA sees considering multiple substitution

A

Poisson correction PC distance = -log(1-p)

kimuras distance = -log(1-p-0.2p^2)

21
Q

what is Jukes Cantor model

A

JC model
model for distance estimation for nucleotides.
assumes equal distance of transversions and transitions. 1 parameter method.
D = -0.75

22
Q

which are trasnversions and transitions?

A
TRANSITIONS
purine to purine = A-G,
pyrimidine to pyrimidine = C-T
TRANSVERSIONS
purine - pyrimidine
23
Q

what is kimuras model for NT distance estimation

A

2 parameter method

transitions are more likely than transversions

24
Q

who made the first phylogenetic tree

A

Ernst Haekel

25
Q
define  (for phylogenetic tree)
root
leaves
branch length
branch
internal node
A
root - common ancestor
leaves - current species
branch length- time
branch - relationship between species
internal node - hypothesised ancestor
26
Q

difference between rooted and unrooted tree

A

rooted tree needs an outgroup for a reference

27
Q

what is a molecular phylogeny tree

A

Phylogenetic tree inferred by nucleotide sequences and/or amino acid sequences

28
Q

ortholog meaning

A

sequences diverged due to speciation

29
Q

paralog meaning

A

sequences diverged due to gene duplication

30
Q

what is advantageous about molecular phylogeny tree?

A

no expertise of morphology needed

universal criteria

31
Q

3 methods for constructing phylogenetic tree

A
  1. distance methods - compute evolution distances for all OTUs and construct a tree which fits.
  2. max parsimony method - choose tree which minimises no. changes required to explain data
  3. max likelihood - choose tree which show highest likelihood for that evolution model.
32
Q

what is UPGMA

A

unweighted pair group method with arithmetic mean
distance between OTUs is an average
uses sequential clustering algorithm. start with things most similar and build composite OTU. see slide 19

  • make matrix of all sequences distance
  • in last column, do average of those seqs.
  • do average of the last column and next one
  • etc
33
Q

weakness of UPGMA method

A

assumes evolutionary rates are the same among different lineages -> if the rates are different among the lineage, the tree is wrong.
produces a rooted tree

34
Q

what is the NJ method

A

neighbour joining
most used method
produced unrooted tree
take into account averaged distances to other leaves (neighbor) as well

35
Q

Maximum parsimony method

A

minimised no changes needed to explain data

36
Q

how is tree root determined?

A
  • between longest route between 2 OTUs
  • add data of reference gene or protein to original, reconstruct tree.
    root places in branch connecting reference and others.
  • use other biological evidence such as gene duplication
37
Q

how to check reliability of phylo tree?

A
  • use bootstrap confidence value
  • choose a random N number of sites - create pseudo alignment
  • make a phylogenetic tree of this pseudo alignment
  • repeat this step hundreds of times
  • count how many topologies support the original one
  • divide my total number of topologies made.
  • gives bootstrap value
38
Q

steps in phylogenetic tree analysis

A
  1. collect sequences
  2. multiple sequence alignment
  3. calculate distance
  4. construction of NJ tree (use Clustalx)
  5. expression of tree image (use NJ plot)
39
Q

what is the purpose of phylogenetic tree analysis?

A

know the phylogenetic relationship of the species
know the evolutionary background
know the orthologous genes of the particular gene

40
Q

3 outcomes of gene duplication

A

pseudogene - non-functionalisation
modified function - sub-fudnctionalisation
new function - neo-functionalisation

41
Q

how are gene duplicates preserved?

A

by Neo-functionalization

gaining a new function

42
Q

what is the 2R hypothesis?

A

vertebrates went through at least one (probably 2-round) whole genome duplications

43
Q

how many genes are under positive selection?

A

5% of all gene families

44
Q

what is molecular drive

A

operates independently of genetic drift and NS.
gene conversion changes genetic composition changes due to certain genes replicating more, giving no biological advantage.

45
Q

what is gene recruitment

A

a gene gets used for a new function in evolution. the gene has pleiotropic effect