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Chapter 5Character–Based Methods of Phylogenetics

暨南大學資訊工程學系黃光璿 (HUANG, Guan-Shieng)2004/04/05

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5.1 Parsimony

Mutations are exceedingly rate 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.

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Ockham's Razor

the philosophic rule that entities should not be multiplied unnecessarily

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5.1.1 Informative and Uninformative Sites

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5.1.1 Informative and Uninformative Sites informative sites

have information to construct a tree uninformative sites

have no information

in the sense of parsimony principle.

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uninformative

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uninformative

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informative

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informative

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

least twice.

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informative sites synapomorphy: support the internal branches

(true) homoplasy: acquired as a result of parallel evol

ution of convergence (false) 眼睛： humans, flies, mollusks ( 軟體動物 )

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5.1.2 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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There are several problems: The number of alternative unrooted trees incre

ases dramatically. Calculating the number of substitutions invoke

d by each alternative tree is difficult.

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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.

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/* the uth position in the kth sequence */

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5.1.4 Weighted Parsimony

Not all mutations are equivalent Some sequences (e.g., non-coding seq.) are mo

re prone to indel than others. Functional importance differs from gene to gen

e. Subtle substitution biases usually vary between

genes and between species. Weights (scoring matrices) can be added t

o reflect these differences.

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Calculating the optimal costs

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Finding the internal nodes

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5.2 Inferred Ancestral Sequences Can be derived while constructing the tree.

No missing link! 如何取樣本 ? It may be bias.

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5.3 Strategies for Faster Searches The number of different phylogenetic tree

grows enormously. 10 sequences 2M for exhaustive search

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5.3.1 Branch and Bound

Provided by Hardy & Penny in 1982.

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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Properties complete search efficient w.r.t. exhaustive search

20 sequences are doable.

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5.3.2 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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5.4 Consensus Trees

Problem Parsimony approaches may yield more than on

e trees. consensus tree

an agreement or a summary of these trees agree bifurcation not agree multi-furcation

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5.5 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?

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5.5.1 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 te

sted one.

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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.

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Strategy doing thousands of iterations using a correction method to adjust for estimati

on biases collapsing branches to multi-furcations

What happens if a tree-building algorithm always produces the same tree?

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5.5.2 Parametric Tests (???)

What is the limit of Parsimony Principle? especially for distant sequences the most parsimonious tree v.s. a particular alte

rnative (this can be used to estimate the significance of the built tree)

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H. Kishino & M. Hasegawa (1989) Assume that informative sites within an alignm

ent are both independent and equivalent. D: difference of minimum number of substitutio

ns invoked by two trees

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5.6 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 .

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5.7 Molecular Phylogenies

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

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5.7.1 The Tree of Life

Carl Woese and his colleagues (1970s) 16S rRNA (all organisms possess)

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5.7.2 Human Origins

mtDNA The mean difference between two human popu

lations is about 0.33%. The greatest differences are found in Alfrica, no

t across the different continents! out-of-Africa theory

mtRNA & Y chromosome are consistent with this hypothesis

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

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參考資料及圖片出處

1. Fundamental Concepts of BioinformaticsDan E. Krane and Michael L. Raymer, Benjamin/Cummings, 2003.

2. Biological Sequence Analysis – Probabilistic models of proteins and nucleic acidsR. Durbin, S. Eddy, A. Krogh, G. Mitchison, Cambridge University Press, 1998.

3. Biology, by Sylvia S. Mader, 8th edition, McGraw-Hill, 2003.