Download Phylogenetics Molecular Phylogenetics

10/20/11
Phylogenetics
Molecular Phylogenetics
• 
• 
• 
Study evolutionary relationships using
DNA, protein
Superior to methods based on
phenotypic characters
Aim:
1.  Order of sequence/species divergences
2.  Time of divergence
3.  Describe sequence of events in lineage
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The time will come, I believe, though I shall not live to
see it, when we shall have fairly true genealogical trees
of each great kingdom of Nature.
Charles Darwin
Phylogenetic Trees
time
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NODE
Hypothetical
Taxonomic Unit
ROOT
BRANCH
Operational
Taxonomic
Unit (OTU)
time
Information
•  Branching order (topology)
–  Relative closeness of different taxa
•  Branch length
–  Amount of divergence
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Rooted and unrooted trees
C
A
D
B
C
A
D
B
E
E
UNROOTED
ROOTED
Rooted and unrooted trees
E
A
B
C
A
D
D
B
E
ROOTED
UNROOTED
C
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Rooted and unrooted trees
A
B
A
E
B
C
D
D
E
UNROOTED
ROOTED
ROOTED
UNROOTED
3 OTUs
B
A
C
4 OTUs
A
B
A
C
C
D
B
A
A
C
B
C
B
C
B
A
A
A
A
B
C
B
C
B
C
D
D
D
A
D
C
C
C
D
A
B
D
B
… 15 rooted trees of 4 OTUs
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Homology
Evolutionary relationship
Related by descent from a common ancestor
Basis of phylogenetics is to compare homologous
characteristics to examine how much they have
changed
- Least change = closest relationship
Homology vs. Analogy
Analogy = similarity due to
convergent evolution
Homologous forelimbs
Analogous wings
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Convergent evolution of analogous burrowing
characteristics
Australian mole
(marsupial)
North American mole
(placental mammal)
Divergence of species from a
common ancestor
Leopard
Domestic cat
Domestic cats did
not evolve from leopards
Common ancestor
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Grouping 2
Grouping 1
D
E
G
C
H
J
F
K
I
B
D
E
G
C
H
J
F
K
I
B
A
(a) Monophyletic. In this tree, grouping 1,
consisting of the seven species B– H, is a
monophyletic group, or clade. A monophyletic group is made up of an
ancestral species (species B in this case)
and all of its descendant species. Only
monophyletic groups qualify as
legitimate taxa derived from cladistics.
Grouping 3
D
E
G
C
H
J
F
K
I
B
A
(b) Paraphyletic. Grouping 2 does not
meet the cladistic criterion: It is
paraphyletic, which means that it
consists of an ancestor (A in this case)
and some, but not all, of that ancestor’s
descendants. (Grouping 2 includes the
descendants I, J, and K, but excludes
B–H, which also descended from A.)
A
(c) Polyphyletic. Grouping 3 also fails the
cladistic test. It is polyphyletic, which
means that it lacks the common ancestor
of (A) the species in the group. Furthermore, a valid taxon that includes the
extant species G, H, J, and K would
necessarily also contain D and E, which
are also descended from A.
Monophyletic & Paraphyletic
Birds
Crocodiles
Snakes and
lizards
REPTILES
Turtles and
tortoises
Mammals
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Monophyletic & Paraphyletic
•  Monophyletic
–  Natural clade; all of the taxa are derived from
a common ancestor
•  Paraphyletic
–  Taxonomic group whose most recent common
ancestor is shared by another taxon
Reconstruct phylogeny from
molecular data
ACTGTTACCGA
?
ACTGTTACCGA
ACTGTTACCGA
ACTGTTACCGA
ACTGTTACCGA
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•  DNA sequences start evolving
independently after speciation or gene
duplication events
•  Recently diverged sequences are more
similar than those from older divergences
•  Sequences accumulate differences over
time
•  Possible to make statistical models for
accumulation of differences
DNA is a good tool for taxonomy
DNA sequences have many advantages over
classical types of taxonomic characters:
–  Character states can be scored unambiguously
–  Large numbers of characters can be scored for
each individual
–  Information on both the extent and the nature of
divergence between sequences is available
(nucleotide substitutions, insertion/deletions, or
genome rearrangements)
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Comparing molecular sequences
•  DNA – 4 bases: A, C, T, G
•  Any base can be substituted by another base with a
single event
•  Protein – 20 amino acids
•  Some amino acid substitutions require more events at
the DNA level
•  Ile  Thr : at least one DNA change
•  AUU  ACU
•  AUC  ACC
•  AUA  ACA
•  Ile  Cys: at least two DNA changes
•  AUU (Ile)  AGU (Ser)  UGU (Cys)
•  AUU (Ile)  UUU (Phe)  UGU (Cys)
Comparing molecular sequences
•  Multiple sequence alignment
•  Align corresponding positions of DNA or
protein sequence
CLUSTAL W(1.60) multiple sequence alignment
CAS1_BOVIN
CAS1_HUMAN
CAS1_MOUSE
CAS1_PIG
CAS1_RABIT
CAS1_RAT
CAS1_SHEEP
MKLLILTCLVAVALARPKHPIKHQGLP-------QEVLNEN-LLRFFVAPFPEVFGKEKV
MRLLILTCLVAVALARPKLPLRYPERLQNP---SESSE-------PIP----LESREEYM
MKLLILTCLVAAAFAMPRLHSRNAVSSQTQQQHSSSEE-------IFKQPKYLNLNQEFV
MKLLIFICLAAVALARPKPPLRHQEHLQNEPDSREELFKERKFLRFPEVPLLSQFRQEII
MKLLILTCLVATALARHKFHLGHLKLTQEQPESSEQEILKERKLLRFVQTVPLELREEYV
MKLLILTCLVAAALALPRAHRRNAVSSQTQQENSSSEEQE-----IVKQPKYLSLNEEFV
MKLLILTCLVAVALARPKHPIKHQGLS-------PEVLNEN-LLRFVVAPFPEVFRKENI
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Methods of Tree reconstruction
•  Distance
•  Maximum Parsimony
•  Maximum Likelihood
Genetic distance
•  Distance from one sequence to another
•  Hamming Distance
–  Count number of differences
•  Construct tree by grouping taxa with
smallest distance first
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Maximum Parsimony
•  Find topology requiring smallest number of
evolutionary changes
•  DNA or protein alignment
•  Sites may be informative or uninformative
•  Uninformative
–  conserved in all taxa
–  Only different in one taxon
•  Informative
–  Favours one topology over others
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Informative sites
a.
b.
c.
d.
A
A
A
A
A
G
G
G
a
c
a
b
d
c
G
C
A
A
A
C
T
G
G
G
A
A
T
T
T
T
T
T
C
C
C
C
C
C
b
c
a
b
d
d
A
T
A
T
Maximum Likelihood
•  Likelihood L of a tree is the probability of
observing the data given the tree
L = P(data|tree)
•  Find the tree with the highest Likelihood
value
•  Results depends on model of nucleotide
substitution
•  Computationally time-consuming
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Outgroup rooting of unrooted trees
•  Outgroup – related sequence that
definitely diverged earlier (paleontological
evidence)
•  Not too distantly related (tree method
becomes unreliable)
chicken
human
mouse
human
mouse
rat
rat
True tree and inferred tree
•  There is only one true tree
•  Represents branching order of species or
sequence divergences
•  Tree inference methods give an answer
•  May not be correct
•  e.g. parsimony method – may get several
equally parsimonious results
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Molecular clock
Molecular phylogenetics
1.  Solved outstanding questions
2.  Drastic revision of traditional view
3.  Pointed to new areas of research
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Molecular Phylogenetics: Case Studies
1. HUMANS AND APES
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Catarrhini taxonomic group: humans, Old World
(African) Monkeys, and apes.
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Apes: Gibbons (southeast Asia) and great apes
(orangutan [southeast Asia]; gorilla, chimpanzee and
bonobo [Africa]).
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Humans were given a separate taxonomic group: Homo
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However, this classification is anthropocentric. All
evidence (morphological and molecular) indicates that
humans belong in the same clade as the African great
apes.
Early molecular studies were
unable to resolve the
relationship of humans to
chimp and gorilla.
Possible phylogenies:
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The evidence
Phylogenetic tree based on the DNA sequence of a mitochondrial gene.
Many other analyses
based on other genes
produced the same tree
topology indicating that
humans and chimps are
more closely related than
either is to gorilla.
2. The relationship of whales
to other mammals
Morphologically, whales,
dolphins and porpoises
(Cetaceans) are quite distinct
from other mammals – made
classical phylogenetic analysis
difficult.
Traditionally, were classified as
close relatives of ungulates
(hoofed mammals), specifically
as relatives of the artiodactyls
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What do the molecular data
say?
DNA analysis of genes from
different mammals indicate
that not only are cetaceans
related to artiodactyls, they
are artiodactyls.
Cetartiodactyls
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3. Where did HIV
come from?
The genome of the HIV
virus is a record of its
evolutionary past.
Closely related viruses
are found in monkeys
(called Simian
Immunodeficiency
viruses [SIV], though
don’t make them sick)
• Have the viruses been around ever since the common
ancestor of humans and monkeys, and only recently became
a problem because of some change in behaviour? Or is there
another explanation for their origin?
Host species tree
If the virus was present in
humans since the common
ancestor with monkeys,
then we would expect that
the topology of the tree of
the viruses is the same as
that of the host.
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The tree of HIV and relatives shows:
1. There is more than one kind of HIV
(HIV-1 and HIV-2)
2. Within each kind of HIV, all the
viruses do not group together
3. The tree topology does not mirror the
known topology of primates.
4. The human viruses are very closely
related to monkey and ape viruses
The molecular data indicate that HIV
came from a zoonotic transmission
from other primates.
HIV1 came from chimp
HIV2 came from Sooty mangabeys.
This is plausible because people living
in the area that is the epicentre for
each of these infections regularly hunt
and eat these primates
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