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CSCE555 Bioinformatics
Lecture 12 Phylogenetics I
HAPPY CHINESE NEW YEAR
Meeting: MW 4:00PM-5:15PM SWGN2A21
Instructor: Dr. Jianjun Hu
Course page: http://www.scigen.org/csce555
University of South Carolina
Department of Computer Science and Engineering
2008 www.cse.sc.edu.
Outline
Introduction to Evolution
 What is phylogeny and phylogenetics
 Application of phylogenetics
 Algorithms for phylogenetic inference

5/24/2017
2
How did life evolve on earth?
An international effort to
understand how life evolved on
earth
Biomedical applications: drug
design, protein structure and
function prediction, biodiversity.

Courtesy of the Tree of Life project
Evolution
Evolution of new organisms
is driven by
 Mutations
◦ The DNA sequence can
be changed due to single
base changes,
deletion/insertion of
DNA segments, etc.
 Selection bias
Theory of Evolution

Basic idea
◦ speciation events lead to creation of
different species.
◦ Speciation caused by physical separation into
groups where different genetic variants
become dominant

Any two species share a (possibly distant)
common ancestor
Primate evolution
A phylogeny is a tree that describes the sequence of
speciation events that lead to the forming of a set of
current day species; also called a phylogenetic tree.
DNA Sequence Evolution
-3 mil yrs
AAGACTT
AAGGCCT
AGGGCAT
AGGGCAT
TAGCCCT
TAGCCCA
-2 mil yrs
TGGACTT
TAGACTT
AGCACTT
AGCACAA
AGCGCTT
-1 mil yrs
today
Morphological vs. Molecular

Classical phylogenetic analysis:
morphological features: number of legs,
lengths of legs, etc.

Modern biological methods allow to use
molecular features
◦ Gene sequences
◦ Protein sequences
◦ Whole genome sequences. E.g.
rearrangements
Morphological topology
(Based on Mc Kenna and Bell, 1997)
Bonobo
Chimpanzee
Man
Gorilla
Sumatran orangutan
Bornean orangutan
Common gibbon
Barbary ape
Baboon
White-fronted capuchin
Slow loris
Tree shrew
Japanese pipistrelle
Long-tailed bat
Jamaican fruit-eating bat
Horseshoe bat
Little red flying fox
Ryukyu flying fox
Mouse
Rat
Vole
Cane-rat
Guinea pig
Squirrel
Dormouse
Rabbit
Pika
Pig
Hippopotamus
Sheep
Cow
Alpaca
Blue whale
Fin whale
Sperm whale
Donkey
Horse
Indian rhino
White rhino
Elephant
Aardvark
Grey seal
Harbor seal
Dog
Cat
Asiatic shrew
Long-clawed shrew
Small Madagascar hedgehog
Hedgehog
Gymnure
Mole
Armadillo
Bandicoot
Wallaroo
Opossum
Platypus
Archonta
Glires
Ungulata
Carnivora
Insectivora
Xenarthra
From sequences to a phylogenetic
tree
Rat
QEPGGLVVPPTDA
Rabbit
QEPGGMVVPPTDA
Gorilla QEPGGLVVPPTDA
Cat
REPGGLVVPPTEG
There are many possible types of
sequences to use (e.g. Mitochondrial vs
Nuclear proteins).
Mitochondrial topology
(Based on Pupko et al.,)
Donkey
Horse
Indian rhino
White rhino
Grey seal
Harbor seal
Dog
Cat
Blue whale
Fin whale
Sperm whale
Hippopotamus
Sheep
Cow
Alpaca
Pig
Little red flying fox
Ryukyu flying fox
Horseshoe bat
Japanese pipistrelle
Long-tailed bat
Jamaican fruit-eating bat
Asiatic shrew
Long-clawed shrew
Mole
Small Madagascar hedgehog
Aardvark
Elephant
Armadillo
Rabbit
Pika
Tree shrew
Bonobo
Chimpanzee
Man
Gorilla
Sumatran orangutan
Bornean orangutan
Common gibbon
Barbary ape
Baboon
White-fronted capuchin
Slow loris
Squirrel
Dormouse
Cane-rat
Guinea pig
Mouse
Rat
Vole
Hedgehog
Gymnure
Bandicoot
Wallaroo
Opossum
Platypus
Perissodactyla
Carnivora
Cetartiodactyla
Chiroptera
Moles+Shrews
Afrotheria
Xenarthra
Lagomorpha
+ Scandentia
Primates
Rodentia 1
Rodentia 2
Hedgehogs
Phylogenenetic trees
Aardvark Bison Chimp Dog
Elephant
Leaves - current day species (or taxa – plural of taxon)
 Internal vertices - hypothetical common ancestors
 Edges length - “time” from one speciation to the next

Types of Trees
A natural model to consider is that of
rooted trees
Common
Ancestor
Types of trees
Unrooted tree represents the same phylogeny
without the root node
Depending on the model, data from current day species does
not distinguish between different placements of the root.
Rooted versus unrooted trees
Tree a
Tree b
Tree c
b
a
c
Represents the three rooted trees
What is phylogenetics?

Phylogenetics is the study of evolutionary
relationships among and within species.
◦ Inference of trees from data
◦ Interpreting the evolutionary tree
◦ Application of evolutionary trees
birds
rodents
crocodiles
marsupials
snakes
primates
lizards
What is phylogenetics?
crocodiles
birds
lizards
snakes
rodents
primates
marsupials
This is an example of a phylogenetic tree.
Applications of phylogenetics
• Forensics:
Did a patient’s HIV infection result from an invasive
dental procedure performed by an HIV+ dentist?
• Conservation:
How much gene flow is there among local populations of
island foxes off the coast of California?
• Medicine:
What are the evolutionary relationships among the
various prion-related diseases?
HIV case
Applications of phylogenetics
1. Forensics

Did a patient’s HIV infection result from
an invasive dental procedure performed
by an HIV+ dentist?
Phylogenetic analysis
So what do the results mean?
• 2 of 3 patients closer to dentist than
to local controls. Statistical
significance? More powerful
analyses?
• Do we have enough data to be
confident in our conclusions?
What additional data would
help?
• If we determine that the dentist’s virus is linked to those of
patients E and G, what are possible interpretations of this
pattern? How could we test between them?
Applications of phylogenetics
2. Conservation
 How much gene flow is there among local
populations of island foxes off the coast of
California?

http://bioquest.org/bedrock/
Wayne, K. R, Morin, P.A. 2004 Conservation Genetics in the New Molecular Age, Frontiers in Ecology and the
Environment. 2: 89-97. (ESA publication)
Applications of phylogenetics
3. Medicine
 What are the evolutionary relationships
among the various prion-related diseases?

Inferring Phylogenies
Trees can be inferred:
◦ Morphology of the organisms
◦ Sequence comparison
Example:
Orc:
ACAGTGACGCCCCAAACGT
Elf:
ACAGTGACGCTACAAACGT
Dwarf:
CCTGTGACGTAACAAACGA
Hobbit:
CCTGTGACGTAGCAAACGA
Human:
CCTGTGACGTAGCAAACGA
How Many Trees?
(assuming bifurcation only)
Unrooted trees
#
#
pairwise
sequences distances
3
4
5
6
10
30
N
# trees
#
branches
/tree
Rooted trees
# trees
# branches
/tree
How Many Trees?
Unrooted trees
Rooted trees
#
sequence
s
#
pairwise
distance
s
3
3
1
3
3
4
4
6
3
5
15
6
5
10
15
7
105
8
6
15
105
9
945
10
10
45
2,027,025
17
34,459,425
18
30
435
8.69  1036
57
4.95  1038
58
N
N (N - 1)
2
#
branches
/tree
# trees
(2N - 5)!
2N - 3 (N - 3)!
2N - 3
# branches
/tree
# trees
(2N - 3)!
2N - 2 (N - 2)!
2N - 2
Phylogenetic Methods
Many different procedures exist. Three of the most
popular:
Neighbor-joining
• Minimizes distance between nearest
neighbors
Maximum parsimony
• Minimizes total evolutionary change
Maximum likelihood
• Maximizes likelihood of observed data
Comparison of Methods
Neighbor-joining
Maximum parsimony
Maximum likelihood
Very fast
Slow
Very slow
Easily trapped in local
optima
Assumptions fail when Highly dependent on
evolution is rapid
assumed evolution model
Good for generating
tentative tree, or choosing
among multiple trees
Best option when
tractable (<30 taxa,
strong conservation)
Good for very small data
sets and for testing trees
built using other methods
Distance based tree Construction


Distance- A weighted tree that realizes the distances
between the objects.
Given a set of species (leaves in a supposed tree), and
distances between them – construct a phylogeny which
best “fits” the distances.
Distance Matrix


Given n species, we can compute the n x n
distance matrix Dij
Dij may be defined as the edit distance
between a gene in species i and species j,
where the gene of interest is sequenced for
all n species.
Distances in Trees
Edges may have weights reflecting:
◦ Number of mutations on evolutionary path from
one species to another
◦ Time estimate for evolution of one species into
another
 In a tree T, we often compute
dij(T) - the length of a path between leaves i and j

Distance in Trees: an Exampe
j
i
d1,4 = 12 + 13 + 14 + 17 + 12 = 68
Fitting Distance Matrix
Given n species, we can compute the n x
n distance matrix Dij
 Evolution of these genes is described by a
tree that we don’t know.
 We need an algorithm to construct a tree
that best fits the distance matrix Dij

Summary
Evolution and Phylogeny
 Concepts of Phylogenetics
 Application of Phylogenetics
 Category of phylogenetic inference algorithms



Next lecture:
Detailed algorithms for phylogenetic inference
Acknowledgement

Anonymous authors