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Phylogenetics

Todd Scheetz

March 23, 2004


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Introduction

Common Terms

General Processes

Types of phylogenetic analyses

PHYLIP and PAUP


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Common TermsPhylogenetics

assessment of the evolutionary relationship betweenspecies, typically utilizing the sequence of a commonmolecule.

DendogramTree-based diagram of phylogenetic structure.

CladeA group of organisms whose members share homologousfeatures derived from a common ancestor.

Taxon (pl. taxa)A category of group such as a phylum, order, species, etc.


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IntroductionThe use of phylogenetics is an attempt to determine how thesequences might have been derived during evolution.

Can be done with both nucleotide or amino acid sequences.

Branching within the tree indicates the apparent relationship between two sequences. Very similar sequences should be nextto each other in the tree.

human

mouse

fly


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Trees

Rooted vs. unrooted trees

Example

GA ATC GA GTT

GA (A/G) T(C/T)


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General ProcessThe basic process of phylogenetic analysis is

1. Alignment

2. Determining the substitution model

3. Tree building

4. Tree evaluation


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What sequence to use?Before performing the analysis, there is a more fundamentalissue to be addressed

What sequences to use?

Guidelines1. Universally present in all organisms to be studied, with

good conservation of sequence amongst many of thespecies.

2. Divergent enough to allow grouping the species into ataxonomic classification.


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Types of SequencesHomologs - Sequences that have a common origin

Orthologs - Homologs derived from speciation

Paralogs - Homologs that derived from a common ancestralgene that underwent duplication and subsequentdivergence.

Xenologs - Homologs resulting from horizontal transfer acrossspecies.


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AlignmentThe first step in performing a phylogenetic analysis is to alignthe sequences. Each column within a multiple sequencealignment is referred to as a site.

Because the sites themselves are effectively assumed to behomologous (share a common ancestor), they represent a priori

phylogenetic conclusions.

Two major steps selection of alignment procedure extracting the phylogenetic data set from the alignment

ARABI GCGCCC ---CAAGCCTTCT-GGCCG---- AGGGCACGTCT

LYCOP GCGCCC ---GAAGCCATTT-GGCCG---- AGGGC......

Taxus GGCCCG ---GAG-C---TC-GGCCG---- AGGGC......

HETER GGCCCC TTT--GGT-ATT----CCGA--- AGG-C...C..

VOLVA GGCCTC TTT--GGCCATT----CCGA--- AGAGC.T.C..


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Alignment ProcedureComputer dependence

unrealistic to do the alignment by handPhylogenetic criteria

does the alignment proceed based upon a tree?EX. clustalw utilizes neighbor joining during sequencealignment

Alignment parameter estimationshould vary dynamically depending on evolutionary distance

Aligned featuressecondary structure -- requires manual intervention

Mathematical optimizationsome programs optimize according to a statistical model, butthis may have unknown effects on further phylogenetic

analysis


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Alignment --

Extracting Phylogenetic InfoThe difficulty here, as we will see on the following page, isthat of length-variable sequences (or alignments).

alignment ambiguitiesindels

1. can remove sites with indels (but lose phylog. signal)2. assign penalty of 0 to indels (but incorr. interp.)3. can treat gap as an additional character 4. treat gap as a new character (but only count firstindel in a series)

Often necessary to use alignment surgery.


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Alignment Procedure

ARABI GCGCCC ---CAAGCCTTCT-GGCCG---- AGGGCACGTCT

LYCOP .....C ---GAAGCCATTT-GGCCG---- A..........

Taxus .GC..G ---GAG-C---TC-GGCCG---- A..........

HETER .....C TTT--GGT-ATT----CCGA--- A..-....C..

VOLVA ....TC TTT--GGCCATT----CCGA--- A.A...T.C..

ARABI GCGCCC ???CAAGCCTTCT?GGCCG???? AGGGCACGTCT ??????????????

LYCOP GCGCCC ???GAAGCCATTT?GGCCG???? AGGGCACGTCT ??????????????TAXUS GGCCCG ???GAG-C?-?TC?GGCCG???? AGGGCACGTCT ??????????????

HETER GCGCCC ??????????????????????? AGG-CACGCCT TTTGGT-ATTCCGA

VOLVA GCGCTC ??????????????????????? AGAGCATGCCT TTTGGCCATTCCGA


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Substitution modelDNA substitution models

Jukes-Cantor - independent probability of substitution at all sites

Kimura - different rates for transitions versus transversionstransition (purine-purine, pyrimidine-pyrimidine, A-G, C-T)transversion (purine-pyrimidine, A-C, A-T, G-C, G-T)

Maximum Likelihood - allows for variations in nucleotide

context, and for different rates for transitions versustransversions.


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Substitution modelAmino Acid substitution models

PAM - uses a PAM001 matrix to create a transition probabilitymatrix between two sequences.

Kimura - approximates PAM distance asD = - ln (1 - p - 0.2p^2)

p = fraction of amino acids that differ

Categories (PHYLIP)1. categories of amino acids2. selectable transition/transversion rates3. selectable genetic codes


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Tree buildingThree fundamental strategies

maximum parsimony distance-based maximum likelihood

Maximum parsimony attempts to minimize the number of stepsrequired to generate the observed variations in the sequences.

Distance-based methods utilize distance metrics to determine

neighboring sequences.

Maximum likelihood method searches for the evolutionarymodel (including the tree) that maximizes the likelihood of

producing the observed data.


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Tree buildingMAXIMUM PARSIMONY

useful for sequence that are very similar, and for small number of sequences.

evaluates all possible trees

only informative sites need to be analyzed,

to be informative, at least two taxa must have the samecharacter at a site, and must support one tree over another...


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Tree buildingMAXIMUM PARSIMONY

Taxa Sequence Positions1 2 3 4 5 6 7 8 9

1 A A G A G T G C A2 A G C C G T G C G3 A G A T A T C C A4 A G A G A T C C G

1

2

3

4

1 2

3 4

1 2

4 3


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Tree buildingDISTANCE-BASED

Fitch-Margolis

Neighbor Joining

UPGMA (Unweighted Pair Group Method with Arithmetic Mean)


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Tree buildingB C D E

A 22 39 39 41B 41 41 43C 18 20

D 10

B C DEA 22 39 40B 41 42

C 19

B CDEA 22 39.66B 41.66

d and e branch lengths= 10/2 = 5 D

E

5

5

DE

C

distance from Cto D and E

= 19/2 = 9.5

5

54.5

9.5

distance from A to B= 22/2 = 11

A

B

11

11


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Tree building

A

B

11

11

So now we have two composite groups...

To unify these, calculate the average distance between the groups= dAC + dAD + dAE + dBC + dBD + dBE= 39+39+41+41+41+43/6 = 40.7

Distance to the Root of the tree is= 40.7/2 = 20.35

DE

C

5

54.5

9.5

A

B

DE

C

5

59.5

4.510.85

9.35 11

11


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Tree buildingMAXIMUM LIKELIHOOD

The likelihood for each individual site within the alignment iscalculated, given a particular tree and the overall observed base

frequencies.

The likelihood of the tree is then the product of the likelihoodsat every site.

The run time is MUCH longer for maximum likelihoodanalyses.


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Tree evaluationThere are two basic strategies for evaluating phylogenetic trees

1. Bootstrap -the original data set is replicated many times, the replicates

are created by sampling the original sites randomly (withreplacement).

2. Jackknife -replicates are created by dropping one or more sites within

each replicate.

A third alternative, is to verify that the tree structure you obtainis consistent among the various construction methods.


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PHYLIPBasic Process

bootseq

consense

tree building program

dnadist

neighbor or fitch

dnapars dnaml

drawtreeor drawgram


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