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Building Phylogenies

Explore building phylogenies using maximum likelihood, distance-based, and parsimony methods in molecular evolution. Learn about hidden ancestral states, transition probabilities, and ancestral reconstruction. Discover how to analyze sites and resolve conflicts in gene duplication scenarios.

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Building Phylogenies

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  1. Building Phylogenies Maximum Likelihood

  2. Methods • Distance-based • Parsimony • Maximum likelihood

  3. Methods • Distance-based • Parsimony • Maximum likelihood

  4. ML is based on a Markov model of evolution • Observed: The species labeling the leaves • Hidden: The ancestral states • Transition probabilities: The mutation probabilities • Assumptions: • Only mutations are allowed • Sites are independent

  5. Models of evolution at a site • Transition probability matrix:M = [mij], i, j{A, C, T, G}where mij = Prob(ij mutation in 1 time unit) • Branches may have different lengths

  6. The probability of an assignment T G T A G C T Probability = mTG ·mGA · mGG · mTT · mTC · mTT

  7. Ancestral reconstruction: most likely assignment X Y Z A G C T L* = maxX,Y,Z {mXY · mYA · mYG· mXZ· mZC· mZT} Compute using Viterbi algorithm

  8. Likelihood of a tree X Y Z A G C T L* = X,Y,Z {mXY · mYA · mYG· mXZ· mZC· mZT} Compute using forward algorithm

  9. Analyzing a site

  10. Analysis for site j

  11. Analysis for all sites Use enumeration (exhaustive, branch and bound, branch swapping, etc.) to find ML tree

  12. Comments • ML is robust • ML converges to correct answer as more data is added • Can put in a Bayesian statistical framework, to obtain a distribution of possible phylogenies • ML can be slow

  13. Complicating factors

  14. Issues • Complicating factors: • Gene duplication • Horizontal gene transfer: Exchange of genetic material between species • Chimeric genes • Evolution may not be described by a tree, but by a network

  15. Gene Duplication  1 2    5’ 3’ human -globin

  16. Homology, orthology, and paralogy • Homology:Similarity attributed to descent from a common ancestor. • Orthologous sequences: Homologous sequences in different species that arose from a common ancestral gene during speciation • May or may not be responsible for a similar function • Paralogous sequences: Homologous sequences within a single species that arose by gene duplication.

  17. Orthology and Paralogy http://www.ncbi.nlm.nih.gov/Education/BLASTinfo/Orthology.html

  18. A A B C C B Conflicts between genes y species? Species Genes

  19.    A B C B A A B C C Resolving the conflict Problem: Resolve conflicts using the minimum number of duplications

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