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Molecular Evolution, Part 2

Molecular Evolution, Part 2

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Molecular Evolution, Part 2

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  1. Molecular Evolution, Part 2 Everything you didn’t want to know… and more!

  2. Average Rates of Substitution

  3. Similarity Profiles

  4. 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

  5. Detecting Positive Selection • Protein coding regions only • KA/KS • Codon-degeneracy model (CDM) • Selection on Amino Acid Properties (TreeSAAP) Case study paper

  6. KA/KS Ratios

  7. 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

  8. MEGA and Positive Selection

  9. Results

  10. Codon Degeneracy

  11. 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

  12. Patterns of Codon-degeneracy

  13. Patterns Applied to the Standard Genetic Code

  14. 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

  15. Central Equations

  16. Nested Newick Trees

  17. Transition Bias

  18. Sliding Window

  19. Results

  20. Amino Acid Properties

  21. Log odds ratio

  22. The .doc format is much clearer. BLOSUM62 Substitution Matrix BLOSUM62 Substitution Matrix

  23. Venn Diagram

  24. Grantham Index • Composition • Polarity • Molecular volume

  25. Physicochemical Distances 20 Mammalian proteins Composition, Polarity, Molecular Weight

  26. 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

  27. The Model Application Description (see pg. 919) • Evolutionary pathways • Counting codons • obs/exp proportions

  28. Amino Acid Properties

  29. Magnitude Categories

  30. Sliding Window

  31. Results