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