Molecular Evolution, Part 2Molecular Evolution, Part 2
Everything you didn’t want to know…and more!
Everything you didn’t want to know…and more!
Average Rates of SubstitutionAverage Rates of Substitution
Similarity ProfilesSimilarity Profiles
What influences determine rates of change & levels of similarity?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 SelectionDetecting Positive Selection
• Protein coding regions only• KA/KS
• Codon-degeneracy model (CDM)• Selection on Amino Acid
Properties (TreeSAAP)Case study paper
KA/KS RatiosKA/KS Ratios
MEGA3MEGA3Molecular 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 SelectionMEGA and Positive Selection
ResultsResults
Codon DegeneracyCodon Degeneracy
CDMCDM• 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-degeneracyPatterns of Codon-degeneracy
Patterns Applied to the Standard Genetic CodePatterns Applied to the Standard Genetic Code
The ModelThe ModelApplication 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 EquationsCentral Equations
Nested Newick TreesNested Newick Trees
Transition BiasTransition Bias
Sliding WindowSliding Window
ResultsResults
Amino Acid PropertiesAmino Acid Properties
Log odds ratioLog odds ratio
3167.0
5.0
fair) is die|six a(get
loaded) is die|six a(get six) aget (
P
PR
48.0)3log( log R
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 21
1
BLOSUM62 Substitution MatrixBLOSUM62 Substitution Matrix
Venn DiagramVenn Diagram
Grantham IndexGrantham Index
• Composition
• Polarity
• Molecular volume
2/1222 ])()()([ jijijiij vvppccD
Physicochemical DistancesPhysicochemical Distances
Composition, Polarity, Molecular Weight
20 Mammalian proteins
TreeSAAPTreeSAAP• 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 ModelThe Model
Application Description
(see pg. 919)
• Evolutionary pathways
• Counting codons
• obs/exp proportions
Amino Acid PropertiesAmino Acid Properties
Magnitude CategoriesMagnitude Categories
Sliding WindowSliding Window
ResultsResults