Introduction to Phylogeny

Lecture Notes for 9 October 2003

CMP 464/788: Introduction to Computational Biology
Prof. St. John
Lehman College
City University of New York

CMP 464/788, 9 October 2003 1

Goal: Reconstruct the Evolutionary History

(www.amnh.org/education/teacherguides/dinosaurs)
Goal: Reconstruct the Evolutionary History

(www.amnh.org/education/teacherguides/dinosaurs)

The evolutionary process not only determines

relationships among taxa, but allows prediction of
structural, physiological, and biochemical properties.
CMP 464/788, 9 October 2003 2
 Process for Reconstruction: Input Data

Start with information about the taxa. For example:

Morphological
Characters
 Process for Reconstruction: Input Data

Start with information about the taxa. For example:

Morphological Biomolecular
Characters Sequences
A GTTAGAAGGCGGCCAGCGAC. . .
B CATTTGTCCTAACTTGACGG. . .
C CAAGAGGCCACTGCAGAATC. . .
D CCGACTTCCAACCTCATGCG. . .
E ATGGGGCACGATGGATATCG. . .
F TACAAATACGCGCAAGTTCG. . .

CMP 464/788, 9 October 2003 3

Process for Reconstruction
 Process for Reconstruction

Input
Data
A GTTAGAAGGC. . .
B CATTTGTCCT. . .
C CAAGAGGCCA. . .
D CCGACTTCCA. . .
E ATGGGGCACG. . .
F TACAAATACG. . .
 Process for Reconstruction

Input Reconstruction
Data Algorithms
A GTTAGAAGGC. . . → Maximum Parsimony
B CATTTGTCCT. . . Maximum Likelihood
C CAAGAGGCCA. . . Distance Methods: NJ,
D CCGACTTCCA. . . Quartet-Based,
E ATGGGGCACG. . . Fast Convering,
F TACAAATACG. . . ..
.
 Process for Reconstruction

Input Reconstruction Output

Data Algorithms Tree
A GTTAGAAGGC. . . → Maximum Parsimony →
B CATTTGTCCT. . . Maximum Likelihood
C CAAGAGGCCA. . . Distance Methods: NJ,
D CCGACTTCCA. . . Quartet-Based,
E ATGGGGCACG. . . Fast Convering,
F TACAAATACG. . . ..
.

CMP 464/788, 9 October 2003 4

 Applications

In addition to finding the evolutionary history of species,

phylogeny is also used for:
 Applications

In addition to finding the evolutionary history of species,

phylogeny is also used for:

• drug discovery: used to determine structural and

biochemical properties of potential drugs
 Applications

In addition to finding the evolutionary history of species,

phylogeny is also used for:

• drug discovery: used to determine structural and

biochemical properties of potential drugs

• determining origins of HIV infection

 Applications

In addition to finding the evolutionary history of species,

phylogeny is also used for:

• drug discovery: used to determine structural and

biochemical properties of potential drugs

• determining origins of HIV infection

• origin of other virus and bacteria strains

CMP 464/788, 9 October 2003 5

 Algorithms for Reconstruction

• Most optimization criteria are hard:

 Algorithms for Reconstruction

• Most optimization criteria are hard:

– Maximum Parsimony: (NP-hard: Foulds & Graham ‘82)
find the tree that can explain the observed sequences with a
minimal number of substitutions.
 Algorithms for Reconstruction

• Most optimization criteria are hard:

– Maximum Parsimony: (NP-hard: Foulds & Graham ‘82)
find the tree that can explain the observed sequences with a
minimal number of substitutions.
– Maximum Likelihood Estimation: find the tree with the
maximum likelihood: P(data|tree).
 Algorithms for Reconstruction

• Most optimization criteria are hard:

– Maximum Parsimony: (NP-hard: Foulds & Graham ‘82)
find the tree that can explain the observed sequences with a
minimal number of substitutions.
– Maximum Likelihood Estimation: find the tree with the
maximum likelihood: P(data|tree).
• For both, the best known algorithms require an
exponential number of trees to be checked.
 Algorithms for Reconstruction

• Most optimization criteria are hard:

– Maximum Parsimony: (NP-hard: Foulds & Graham ‘82)
find the tree that can explain the observed sequences with a
minimal number of substitutions.
– Maximum Likelihood Estimation: find the tree with the
maximum likelihood: P(data|tree).
• For both, the best known algorithms require an
exponential number of trees to be checked.
This is not feasible for more than 20 taxa.

CMP 464/788, 9 October 2003 6

 Approximation Algorithms

• Since calculating the exact answer is hard, algorithms

that estimate the answer have been developed.
 Approximation Algorithms

• Since calculating the exact answer is hard, algorithms

that estimate the answer have been developed.
– Heuristics for maximum parsimony and maximum
likelihood estimation
(use clever ways to limit the number of trees checked, while still
sampling much of “tree-space”)
 Approximation Algorithms

• Since calculating the exact answer is hard, algorithms

that estimate the answer have been developed.
– Heuristics for maximum parsimony and maximum
likelihood estimation
(use clever ways to limit the number of trees checked, while still
sampling much of “tree-space”)
– Polynomial-time methods, based on the distance
between taxa

CMP 464/788, 9 October 2003 7

 Distance-Based Methods

• These methods calculate the distance between taxa:

B D A C F E
B 0 0.496505 0.496505 0.444519 0.375798 0.268166
D 0.496505 0 0.496505 0.375798 0.275673 0.279728
A 0.496505 0.496505 0 0.362124 0.323812 0.496505
C 0.444519 0.375798 0.362124 0 0.496505 0.496505
F 0.375798 0.275673 0.323812 0.496505 0 0.496505
E 0.268166 0.279728 0.496505 0.496505 0.496505 0

and then determine the tree using the distance matrix.

 Distance-Based Methods

• These methods calculate the distance between taxa:

B D A C F E
B 0 0.496505 0.496505 0.444519 0.375798 0.268166
D 0.496505 0 0.496505 0.375798 0.275673 0.279728
A 0.496505 0.496505 0 0.362124 0.323812 0.496505
C 0.444519 0.375798 0.362124 0 0.496505 0.496505
F 0.375798 0.275673 0.323812 0.496505 0 0.496505
E 0.268166 0.279728 0.496505 0.496505 0.496505 0

and then determine the tree using the distance matrix.

• One way to calculate distance is to take differences
divided by the length (the normalized Hamming distance).

CMP 464/788, 9 October 2003 8

 Distance-Based Methods
• Popular distance based methods include
 Distance-Based Methods
• Popular distance based methods include
– Neighbor Joining (Saitou & Nei ‘87) which repeatedly
joins the “nearest neighbors” to build a tree, and
 Distance-Based Methods
• Popular distance based methods include
– Neighbor Joining (Saitou & Nei ‘87) which repeatedly
joins the “nearest neighbors” to build a tree, and
– Quartet-based methods that decide the topology for
every 4 taxa and then assemble them to form a tree
(Berry et al. 1999, 2000, 2001).
 Distance-Based Methods
• Popular distance based methods include
– Neighbor Joining (Saitou & Nei ‘87) which repeatedly
joins the “nearest neighbors” to build a tree, and
– Quartet-based methods that decide the topology for
every 4 taxa and then assemble them to form a tree
(Berry et al. 1999, 2000, 2001).

• Many of these methods have good performance

empirically, and some can be proven to have nice
accuracy properties.
CMP 464/788, 9 October 2003 9
 Testing Methods Empirically
• How accurate are the methods at reconstructing trees?
 Testing Methods Empirically
• How accurate are the methods at reconstructing trees?

• In biological applications, the true, historical tree is

almost never known, which makes assessing the quality
of phylogenetic reconstruction methods problematic.
 Testing Methods Empirically
• How accurate are the methods at reconstructing trees?

• In biological applications, the true, historical tree is

almost never known, which makes assessing the quality
of phylogenetic reconstruction methods problematic.
(an exception: Hillis ‘92 created an evolutionary tree in the
laboratory)
 Testing Methods Empirically
• How accurate are the methods at reconstructing trees?

• In biological applications, the true, historical tree is

almost never known, which makes assessing the quality
of phylogenetic reconstruction methods problematic.
(an exception: Hillis ‘92 created an evolutionary tree in the
laboratory)

• Simulation is used instead to evaluate methods, given

a model of evolution.
CMP 464/788, 9 October 2003 10
 Simulation Studies

1. Construct a
“model” tree.
 Simulation Studies

1. Construct a 2. “Evolve”
“model” tree. sequences down
the tree.

A GTTAGAAGGCGGCCA. . .
B CATTTGTCCTAACTT. . .
C CAAGAGGCCACTGCA. . .
D CCGACTTCCAACCTC. . .
E ATGGGGCACGATGGA. . .
F TACAAATACGCGCAA. . .
 Simulation Studies

1. Construct a 2. “Evolve” 3. Reconstruct

“model” tree. sequences down the tree using
the tree. method.

A GTTAGAAGGCGGCCA. . .
B CATTTGTCCTAACTT. . .
C CAAGAGGCCACTGCA. . .
D CCGACTTCCAACCTC. . .
E ATGGGGCACGATGGA. . .
F TACAAATACGCGCAA. . .
 Simulation Studies

1. Construct a 2. “Evolve” 3. Reconstruct

“model” tree. sequences down the tree using
the tree. method.

A GTTAGAAGGCGGCCA. . .
B CATTTGTCCTAACTT. . .
C CAAGAGGCCACTGCA. . .
D CCGACTTCCAACCTC. . .
E ATGGGGCACGATGGA. . .
F TACAAATACGCGCAA. . .

4. Evaluate the accuracy of the constructed tree.

CMP 464/788, 9 October 2003 11

 Simulation Studies

1. Construct a 2. “Evolve” 3. Reconstruct

“model” tree. sequences down the tree using
the tree. method.

A GTTAGAAGGCGGCCA. . .
B CATTTGTCCTAACTT. . .
C CAAGAGGCCACTGCA. . .
D CCGACTTCCAACCTC. . .
E ATGGGGCACGATGGA. . .
F TACAAATACGCGCAA. . .

4. Evaluate the accuracy of the constructed tree.

CMP 464/788, 9 October 2003 12