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"Microbial Phylogenomics"

Taught by Jonathan Eisen and Cassie Ettinger.

Winter 2018.

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Science

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- 1. Class 1: EVE 161: Microbial Phylogenomics Class #4: Phylogeny UC Davis, Winter 2018 Instructor: Jonathan Eisen Teaching Assistant: Cassie Ettinger !1
- 2. Where we are going and where we have been • Previous Class: !3. rRNA • Current Class: !4. Phylogeny • Next Class: !5. Tree of Life !2
- 3. Phylogeny • Eisen Make Up Office Hours Tomorrow • Storer 5331 10:30-11:30 • Cassie Ettinger Office Hours • Today Storer 5331 10:30-11:30
- 4. Phylogeny Phylogeny
- 5. First Phylogenetic Tree?
- 6. Internal nodes represent hypothetical ancestral taxa a b c d e f g h root, root node terminal (or tip) taxa internal nodes internal branches u v w x y z t Terminal branches Parts of a phylogenetic tree !6
- 7. Branch Rotation
- 8. Types of Trees
- 9. Phylogram (Tree with Lengths)
- 10. Phylogenetic Groups
- 11. Phylogenetic Groups Monophyletic Paraphyletic Polyphyletic
- 12. Branch rotation
- 13. Characters • A heritable feature of an organism is known as a character (also character trait or trait). • The form that a character takes is known as its state (also known as character state). ! Note: Presence/absence can be a state • Example: ! Character = heart ! Character state = present/absent ! Character state = # of chambers !13
- 14. Characters ancestry is critical to understand • Characters that are inherited from a common ancestor are homologous. • Species change over time ! Known (generally) as divergence, or divergent evolution. ! Species change over time due to the combined processes of mutation, recombination, drift, selection, etc !14
- 15. Homology vs. Orthology vs. Paralogy
- 16. Data matrices !16
- 17. Alignment
- 18. Alignment with Gaps
- 19. Sequence Alignment 19
- 20. Alignment Scoring (BLAST)
- 21. DNA substitution matrix
- 22. Blosum Matrix
- 23. Guide Tree for Alignment
- 24. Refining Alignment
- 25. Structure Guided Alignment
- 26. Structure Guided Alignment
- 27. HMM Alignment
- 28. Tree reconstruction methods 28
- 29. Distance Phylogenetics • Calculate distances between taxa • Use an algorithm to infer a tree from those distances • Based on principle that divergence occurs after organisms separate
- 30. Parimony Phylogenetics • Based on Principle of Parsimony / Occam’s Razor • Possible trees are given a score of the fewest number of sequence changes required to fit data into tree • Score for all possible trees
- 31. Likelihood Phylogenetics • Based on Bayes’ Theorem • Trying to calculate the Probability of the Data, Given a Hypothesis • For each tree, calculate probability that the data (e.g., sequence alignment) could come from that tree • Score for all possible trees • Prob(H|D) = Prob(H and D) ÷ Prob(D) • Prob(H|D) = Prob(D|H) x Prob(H) ÷ Prob(D)
- 32. Bayesian Phylogenetics • Based on Bayes’ Theorem • Trying to calculate the Probability of the Hypothesis, Given the Data • For each tree, calculate probability that the tree could come from that data ((e.g., sequence alignment) • Score for all possible trees • Prob(H|D) = Prob(H and D) ÷ Prob(D) • Prob(H|D) = Prob(D|H) x Prob(H) ÷ Prob(D)
- 33. Bayesian • Based on Bayes’ Theorem • Prob(H|D) = Prob(H and D) ÷ Prob(D) • Prob(H|D) = Prob(D|H) x Prob(H) ÷ Prob(D)
- 34. Many possible trees
- 35. Other Tree Related Issues
- 36. Bootstrapping
- 37. Bootstrapping !37
- 38. Jacknifing !38
- 39. Congruence !39
- 40. Masking !40
- 41. Concatenation !41
- 42. Homoplasy !42
- 43. Clustering vs. Distance Trees
- 44. UPGMA Unweighted Pair Group Method with Arithmetic mean (UPGMA) algorithm
- 45. The True Tree
- 46. Distance Matrix For True Tree
- 47. Collapse Diagonal
- 48. Identify Lowest D OTUs A B C D E B 2 C 4 4 D 6 6 6 E 6 6 6 4 F 8 8 8 8 8
- 49. Join Those Two Taxa • Create branch with length = D • 2 • A--------------B
- 50. Make D from Node Equal
- 51. Create New Distance Matrix • Merge Two OTUs joined in previous step (AB) • Dx, AB = 0.5 * (Dx, A + Dx, B)
- 52. New Matrix
- 53. UPGMA
- 54. Compare to True Tree
- 55. But … • What is evolutionary rates not equal
- 56. Unequal rates
- 57. UPGMA with Unequal rates
- 58. Compare to True Tree
- 59. Neighbor Joining
- 60. Start with Star Tree
- 61. Calculate S • For each OTU, calculate a measure (S) as follows. • S is the sum of the distances (D) between that OTU and every other OTU, divided by N-2 where N is the total number of OTUs. • This is a measure of the distance an OTU is from all other OTUs
- 62. Calculate Pairwise Distances • Calculate the distance Dij between each OTU pair (e.g., I and J).
- 63. Identify Closest Pair • Identify the pair of OTUs with the minimum value of Dij – Si – Sj
- 64. Joining Taxa • As in UPGMA, join these two taxa at a node in a subtree.
- 65. Calculate Branches • Calculate branch lengths. Unlike UPGMA, neighbor joining does not force the branch lengths from node X to I (Dxi) and to J (Dxj) to be equal, i.e., does not force the rate of change in those branches to be equal. Instead, these distances are calculated according to the following formulas • Dxi = 1/2 Dij + 1/2 (Si – Sj) • Dxj = 1/2 Dij + 1/2 (Sj – Si)
- 66. Calculate New Matrix • Calculate a new distance matrix with I and J merged and replaced by the node (X) that joins them. Calculate the distances from this node to the other tips (K) by: • Dxk = (Dik + Djk – Dij)/2
- 67. Distance Matrix
- 68. S • SA = (5+4+7+6+8) / 4 = 7.5 • SB = (5+7+10+9+11) / 4 = 10.5 • SC = (4+7+7+6+8) / 4 = 8 • SD= (7+10+7+5+9) / 4 = 9.5 • SE= (6+9+6+5+8) / 4 = 8.5 • SF= (8+11+8+9+8) / 4 = 11
- 69. M • Mij = Dij – Si - Sj • Smallest are • MAB = 5 – 7.5 – 10.5 = -13 • MDE = 5 – 9.5 – 8.5 = -13 • Choose one of these (AB here)
- 70. New Tree • Create a node (U) that joins pair with lowest Mij such that • SIU = DIJ/2 + (SI – SJ) / 2 • Merge U with other taxa • Join I and J according to S above and make all other taxa in form of a star
- 71. C D E F U1 B A 4 1
- 72. New Matrix • DXU = DIX + DJX – DIJ where I and J are those selected from above.
- 73. Table 11
- 74. Compare to True Tree C D E F U1 B A 4 1 U2 3 2 2 1 U3 U4 5
- 75. Long branch attraction !75
- 76. Rooting !76
- 77. Rooting TOL Review

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