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Introduction to Phylogenetics

Introduction to Phylogenetics. Download the PPT file…. Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services http:// mcarthurbioinformatcs.ca. An Example: CYP3A Phylogeny. McArthur et al. 2003. J. Mol. Evol . 57: 200-211. MBL-TIGR Advances in Genome Technology and Bioinformatics.

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Introduction to Phylogenetics

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  1. Introduction to Phylogenetics Download the PPT file… Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services http://mcarthurbioinformatcs.ca

  2. An Example: CYP3A Phylogeny McArthur et al. 2003. J. Mol. Evol. 57: 200-211. MBL-TIGR Advances in Genome Technology and Bioinformatics Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  3. An Example: CYP3A Phylogeny Outgroup choice is important McArthur et al. 2003. J. Mol. Evol. 57: 200-211. Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  4. An Example: CYP3A Phylogeny Outgroup choice is important Trees can reflect gene duplication McArthur et al. 2003. J. Mol. Evol. 57: 200-211. Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  5. An Example: CYP3A Phylogeny Outgroup choice is important Trees can reflect gene duplication Trees can reflect speciation McArthur et al. 2003. J. Mol. Evol. 57: 200-211. Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  6. An Example: CYP3A Phylogeny Outgroup choice is important Trees can reflect gene duplication Trees can reflect speciation Trees can be a combination of gene trees and species trees McArthur et al. 2003. J. Mol. Evol. 57: 200-211. Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  7. An Example: CYP3A Phylogeny Outgroup choice is important Trees can reflect gene duplication Trees can reflect speciation Trees can be a combination of gene trees and species trees Trees should include confidence estimates McArthur et al. 2003. J. Mol. Evol. 57: 200-211. Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  8. An Example: CYP3A Phylogeny Outgroup choice is important Trees can reflect gene duplication Trees can reflect speciation Trees can be a combination of gene trees and species trees Trees should include confidence estimates Trees include estimates of evolutionary distance McArthur et al. 2003. J. Mol. Evol. 57: 200-211. Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  9. An Example: CYP3A Phylogeny Outgroup choice is important Trees can reflect gene duplication Trees can reflect speciation Trees can be a combination of gene trees and species trees Trees should include confidence estimates Trees include estimates of evolutionary distance Branch lengths are a function of time and rate of evolution Dali, Persistence of Time Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  10. Substitution & Rates of Evolution Ancestral Sequence Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  11. Substitution & Rates of Evolution Ancestral Sequence gene duplication t t Sequence 1 Sequence 2 Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  12. Substitution & Rates of Evolution A No Change gene duplication t t A A Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  13. Substitution & Rates of Evolution A Single Substitution gene duplication t t C A Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  14. Substitution & Rates of Evolution A Multiple Substitutions gene duplication T False sequence similarity! C C Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  15. Key Issues of Phylogenetics How do we model substitution? How do we search for the best tree? Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  16. Key Issues of Phylogenetics PARSIMONY DISTANCE METHODS (neighbour-joining, minimum evolution) MAXIMUM LIKELIHOOD BAYESIAN INFERENCE Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  17. Key Issues of Phylogenetics DISTANCE METHODS (neighbour-joining, minimum evolution) Simplify a multiple sequence alignment to a distance matrix Loss of information; unreliable method Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  18. Key Issues of Phylogenetics PARSIMONY DISTANCE METHODS (neighbour-joining, minimum evolution) MAXIMUM LIKELIHOOD BAYESIAN INFERENCE Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  19. Ignoring Multiple Substitutions: Parsimony A A ? A ? A C G Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  20. Ignoring Multiple Substitutions: Parsimony A A A A ? A C G Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  21. Ignoring Multiple Substitutions: Parsimony A A A A C A C G Score: Two changes Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  22. Ignoring Multiple Substitutions: Parsimony A A A A A A C G Score: Two changes Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  23. Ignoring Multiple Substitutions: Parsimony A A A A G A C G Score: Two changes Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  24. Ignoring Multiple Substitutions: Parsimony A A A A T A C G Score: Three changes Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  25. Ignoring Multiple Substitutions: Parsimony A A A A C/G/A A C G NO SUBSTITUTION MODEL! LACK OF RESOLUTION! Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  26. Key Issues of Phylogenetics PARSIMONY DISTANCE METHODS (neighbour-joining, minimum evolution) MAXIMUM LIKELIHOOD BAYESIAN INFERENCE Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  27. Accounting for Multiple Substitutions: Likelihood A A ? A ? A C G Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  28. Accounting for Multiple Substitutions: Likelihood A A A A ? A C G Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  29. Accounting for Multiple Substitutions: Likelihood A A A A T A C G Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  30. Accounting for Multiple Substitutions: Likelihood A A A A G>t A C G Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  31. Accounting for Multiple Substitutions: Likelihood A A A A C>g>t A C G Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  32. Accounting for Multiple Substitutions: Likelihood A A A A A>c>g>t A C G BRANCH LENGTHS COME FROM A SUBSTITUTION MODEL A SUBSTITUTION MODEL ADDS RESOLUTION! Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  33. Accounting for Multiple Substitutions: Likelihood A A A A A>c>g>t A C G What about transition/transversion bias or synonymous/non-synonymous substitution bias? BRANCH LENGTHS COME FROM A SUBSTITUTION MODEL A SUBSTITUTION MODEL ADDS RESOLUTION! Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  34. Substitution Models Empirical Theoretical A C G T ProtTest 3: fast selection of best-fit models of protein evolution. Bioinformatics 27:1164-5. Ca Gb Tc A jModelTest: phylogenetic model averaging. Molecular Biology and Evolution 25: 1253-1256. Gd Te C Tf G T Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  35. A A A A A>c>g>t A C G SCORE A C G T Ca Gb Tc A Gd Te C Tf G T Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  36. A A A A Among Site Rate Variation A>c>g>t A C G SCORE A C G T Ca Gb Tc A Gd Te C Tf G T Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  37. How Do We Find The Best Tree? Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  38. Key Issues of Phylogenetics PARSIMONY DISTANCE METHODS (neighbour-joining, minimum evolution) MAXIMUM LIKELIHOOD – branch swapping, find the best tree BAYESIAN INFERENCE – MC3, sample the cloud of best trees Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

  39. Branch Swapping

  40. Branch Swapping

  41. Branch Swapping

  42. Branch Swapping branch swapping

  43. Branch Swapping

  44. Branch Swapping

  45. Branch Swapping

  46. Branch Swapping

  47. Branch Swapping

  48. Branch Swapping Local optima

  49. Branch Swapping Best Tree! Replicates!

  50. Key Issues of Phylogenetics PARSIMONY DISTANCE METHODS (neighbour-joining, minimum evolution) MAXIMUM LIKELIHOOD – branch swapping, find the best tree – how many branch swapping replicates? BAYESIAN INFERENCE – MC3, sample the cloud of best trees Andrew G. McArthur, Ph.D., Bioinformatics Consulting Services

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