Download Molecular Evolution, Part 2

Molecular
Evolution, Part 2
Everything you didn’t want to know…
and more!
Average Rates of
Substitution
Similarity Profiles
What influences determine rates
of change & levels of similarity?
• Mutation – stochastic changes
• Natural selection – organismal
survival and reproductive success
• Genetic drift – random fixation of
selectively neutral alleles
Detecting Positive
Selection
•
•
•
•
Protein coding regions only
KA/KS
Codon-degeneracy model (CDM)
Selection on Amino Acid
Properties (TreeSAAP)
Case study paper
KA/KS Ratios
MEGA3
Molecular Evolutionary Genetics Analysis
www.megasoftware.net/mega3/
1. Constructing Trees from Distance Data
2. Computing Statistical Quantities for Nucleotide Sequences
3, Estimating Evolutionary Distances from Nucleotide Sequences
4. Constructing Trees and Selecting OTUs from Nucleotide Sequences
5. Tests of the Reliability of a Tree Obtained
6. Test of Positive Selection
7. Creating Multiple Sequence Alignments
8. Working With Genes and Domains
9. Managing Taxa With Groups
Application Description
MEGA and Positive
Selection
Results
Codon Degeneracy
CDM
• Uses the degeneracy structure of codons to
predict patterns of nucleotide substitution
expected under neutral expectations
• Expectations are statistically compared to
observations inferred from a well-resolved
phylogenetic tree
• Deviations from neutral expectations indicates
a significant historical influence by natural
selection on the protein
Patterns of
Codon-degeneracy
Patterns Applied to the
Standard Genetic Code
The Model
Application Descriptions: 1, 2, 3
(See pg. 395 of #3)
• Patterns of codon degeneracy
• Counting sites
• Counting codons with certain patterns of
degeneracy
• Transition bias
• Evolvability – codon architecture
Central Equations
Nested Newick Trees
Transition Bias
Sliding Window
Results
Amino Acid Properties
Log odds ratio
P(get a six | die is loaded)
0.5
R(get a six) 

3
P(get a six | die is fair)
0.167
log R  log( 3)  0.48
BLOSUM62 Substitution Matrix
C
S
T
P
A
G
N
D
E
Q
H
R
K
M
I
L
V
F
Y
W
C
9
-1
-1
-3
0
-3
-3
-3
-4
-3
-3
-3
-3
-1
-1
-1
-1
-2
-2
-2
S
-1
4
1
-1
1
0
1
0
0
0
-1
-1
0
-1
-2
-2
-2
-2
-2
-3
T
-1
1
4
1
-1
1
0
1
0
0
0
-1
0
-1
-2
-2
-2
-2
-2
-3
P
-3
-1
1
7
-1
-2
-1
-1
-1
-1
-2
-2
-1
-2
-3
-3
-2
-4
-3
-4
A
0
1
-1
-1
4
0
-1
-2
-1
-1
-2
-1
-1
-1
-1
-1
-2
-2
-2
-3
G
-3
0
1
-2
0
6
-2
-1
-2
-2
-2
-2
-2
-3
-4
-4
0
-3
-3
-2
N
-3
1
0
-2
-2
0
6
1
0
0
-1
0
0
-2
-3
-3
-3
-3
-2
-4
D
-3
0
1
-1
-2
-1
1
6
2
0
-1
-2
-1
-3
-3
-4
-3
-3
-3
-4
E
-4
0
0
-1
-1
-2
0
2
5
2
0
0
1
-2
-3
-3
-3
-3
-2
-3
Q
-3
0
0
-1
-1
-2
0
0
2
5
0
1
1
0
-3
-2
-2
-3
-1
-2
H
-3
-1
0
-2
-2
-2
1
1
0
0
8
0
-1
-2
-3
-3
-2
-1
2
-2
R
-3
-1
-1
-2
-1
-2
0
-2
0
1
0
5
2
-1
-3
-2
-3
-3
-2
-3
K
-3
0
0
-1
-1
-2
0
-1
1
1
-1
2
5
-1
-3
-2
-3
-3
-2
-3
M
-1
-1
-1
-2
-1
-3
-2
-3
-2
0
-2
-1
-1
5
1
2
-2
0
-1
-1
I
-1
-2
-2
-3
-1
-4
-3
-3
-3
-3
-3
-3
-3
1
4
2
1
0
-1
-3
L
-1
-2
-2
-3
-1
-4
-3
-4
-3
-2
-3
-2
-2
2
2
4
3
0
-1
-2
V
-1
-2
-2
-2
0
-3
-3
-3
-2
-2
-3
-3
-2
1
3
1
4
-1
-1
-3
F
-2
-2
-2
-4
-2
-3
-3
-3
-3
-3
-1
-3
-3
0
0
0
-1
6
3
1
Y
-2
-2
-2
-3
-2
-3
-2
-3
-2
-1
2
-2
-2
-1
-1
-1
-1
3
7
2
W
-2
-3
-3
-4
-3
-2
-4
-4
-3
-2
-2
-3
-3
-1
-3
-2
-3
1
2
1
1
Venn Diagram
Grantham Index
• Composition
• Polarity
• Molecular volume
Dij  [ (ci  c j )   ( pi  p j )   (vi  v j ) ]
2
2
2 1/ 2
Physicochemical
Distances
20 Mammalian proteins
Composition, Polarity,
Molecular Weight
TreeSAAP
• Assumes that all possible changes are
equally likely to construct a discrete
probability distribution of magnitudes of
biochemical change for alternative
physicochemical amino acid properties
• Statistically compares these expectations with
observed biochemical changes
• Deviations from constrained randomness
indicate positive or negative selection
The Model
Application Description
(see pg. 919)
• Evolutionary pathways
• Counting codons
• obs/exp proportions
Amino Acid Properties
Magnitude Categories
Sliding Window
Results