1 Chapter 5 Character–Based Methods of Phylogenetics 暨南大學資訊工程學系 黃光璿 (HUANG, Guan-Shieng) 2004/04/05

2 5.1 Parsimony Mutations are exceedingly rare events. The most unlikely events a model invokes, the less likely the model is to be correct.  The fewest number of mutations to explain a state is the most likely to be correct.

3 Ockham's Razor the philosophic rule states that entities should not be multiplied unnecessarily

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Informative and Uninformative Sites

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8 informative sites  have information to construct a tree uninformative sites  have no information in the sense of parsimony principle.

9 uninformative

10 uninformative

11 informative

12 informative

13 A position to be informative must have  at least two different nucleotides  each of these nucleotides to present at least twice.

14 informative sites  synapomorphy: support the internal branches (true)  homoplasy: acquired as a result of parallel evolution of convergence (false) 眼睛： humans, flies, mollusks ( 軟體動物 )

Unweighted Parsimony Every possible tree is considered individually for each informative site. The tree with the minimum overall costs are reported.

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17 There are several problems:  The number of alternative unrooted trees increases dramatically.  Calculating the number of substitutions invoked by each alternative tree is difficult.

18 The second problem can be solved by  intersection: if the intersection of the two sets of its children is not empty  union: if it is empty.  The number of unions is the minimum number of substitutions.  For uninformative site, it is the number of different nucleotides minus one.

19 /* the u th position in the k th sequence */

Weighted Parsimony Not all mutations are equivalent  Some sequences (e.g., non-coding seq.) are more prone to indel than others.  Functional importance differs from gene to gene.  Subtle substitution biases usually vary between genes and between species.  Weights (scoring matrices) can be added to reflect these differences.

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25 Calculating the optimal costs

26 Finding the internal nodes

Inferred Ancestral Sequences Can be derived while constructing the tree.   No missing link! 如何取樣本 ? It may be bias.

Strategies for Faster Searches The number of different phylogenetic tree grows enormously.  10 sequences  2M for exhaustive search

Branch and Bound Provided by Hardy & Penny in L: an upper bound (for minimum problem)  obtained from random search or by heuristics (e.g., UPGMA) Incrementally growing a tree. (branch) Prune any branch with cost already greater than L. (bound)

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31 Properties  complete search  efficient w.r.t. exhaustive search 20 sequences are doable.

Heuristic Searches local search  Alternative trees are not all independent of each other.  branch swapping (Fig. 5.5) Properties  not complete, may lose the optimal solution  fast and efficient  local minimal

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Consensus Trees Problem  Parsimony approaches may yield more than one trees. consensus tree  an agreement or a summary of these trees agree  bifurcation not agree  multi-furcation

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Tree Confidence How much confidence can be attached to the overall tree and its component parts How much more likely is one tree to be correct than a particular or randomly chosen alternative tree?

Bootstrap Tests 1. Randomly choose columns to combine into a new alignment of the same order. 2. Reconstruct the tree for the new sample. 3. Repeat (1) (2) for many times. 4. Consensus the sampled trees w.r.t. the tested one.

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42 Caution  Test based on fewer than several hundred iterations are not reliable.  Underestimate the confidence level at high values and overestimate it at low values.  Some results may appear to be statistically significant by chance simply so many groupings are being considered.

43 Strategy  doing thousands of iterations  using a correction method to adjust for estimation biases  collapsing branches to multi-furcations What happens if a tree-building algorithm always produces the same tree?

Parametric Tests (???) What is the limit of Parsimony Principle?  especially for distant sequences  the most parsimonious tree v.s. a particular alternative (this can be used to estimate the significance of the built tree)

45 H. Kishino & M. Hasegawa (1989)  Assume that informative sites within an alignment are both independent and equivalent.  D: difference of minimum number of substitutions invoked by two trees

Comparison of Phylogenetic Methods 用兩種不同的方法, 如果建構出相同的樹, 那 麼其正確性就很高.

Molecular Phylogenies Implications  medicine: drug treatment  agriculture: disease resistance factors  conservation ( 保育 ): 絕種物種之認定

The Tree of LifeThe Tree of Life Carl Woese and his colleagues (1970s)  16S rRNA (all organisms possess)

Human Origins mtDNA  The mean difference between two human populations is about 0.33%.  The greatest differences are found in Alfrica, not across the different continents!  out-of-Africa theory  mtRNA & Y chromosome are consistent with this hypothesis

50 They concluded  mitochondrial Eve & Y chromosome Adam  200’000 years ago

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52 參考資料及圖片出處 1. Fundamental Concepts of Bioinformatics Dan E. Krane and Michael L. Raymer, Benjamin/Cummings, Fundamental Concepts of Bioinformatics 2. Biological Sequence Analysis – Probabilistic models of proteins and nucleic acids R. Durbin, S. Eddy, A. Krogh, G. Mitchison, Cambridge University Press, Biological Sequence Analysis 3. Biology, by Sylvia S. Mader, 8th edition, McGraw-Hill, Biology