Genes and Evolution
Molecular clocks and phylogenies
Systematics A definition of taxonomy
Phylogenies Characters and traits
Homology and homoplasty
Simple Phylogenies
Molecular evolution
Substitutions
Synonymous and nonsynonymous
Selection and neutral theory
Molecular phylogenies
Molecular clocks
Adam Price
Defining Systematics and Taxonomy
Systematics- the study of the diversity of organisms
Taxonomy- the science of classification of organisms
taxis = Greek to arrange, classify
Why?
Explains evolutionary relationships
Intrinsically interested
Underpins an understanding of biology- e.g. ecology, conservation
Important in applications to human life
Phylogeny- the history of descent of a group of organisms from
a common ancestor
from Greek- phylon = tribe, race genesis = source
Conventionally represented by a phylogeneic tree
Monkey
Gorilla
Chimpanzee
Human
Ferns
Conifers
Peas
Rice
Phylogenic trees
Phylogentic trees are based on comparison of traits
individuals with common traits are placed together
Character = a feature of the organisms (e.g. flower colour, height)
Trait = one form of a character (blue flower colour, short height)
Traits inherited from a common ancestor are termed
homologous
Traits that differs from the ancestor are termed derived
Phylogenies are trees that best explain the distribution of
homologous and derived traits in the organisms studied (the
focal group).
Scoring traits to make a simple phylogeny
Taxon
Hagfish
Perch
Salamander
Lizard
Crocodile
Pigeon
Mouse
Chimpanzee
Jaws
Lungs
+
+
+
+
+
+
+
+
+
+
+
+
+
Claws or
nails
+
+
+
+
+
Derived trait
Feathers
Fur
+
-
+
+
Mammary
glands
+
+
Four-chambered
heart
+
+
+
+
A simple phylogeny
Hagfish
Perch
Jaws
Salamander
Lungs
Lizard
Claws or
nails
Crocodile
Feathers
Four-chambered
heart
Pigeon
Mouse
Fur, mammary
glands
Chimpanzee
Relative evolutionary time
Ancient events
Recent events
Phylogenetic trees
Outgroup
Paraphyletic
Polyphyletic
Monophyletic
Monophyletic taxa include all descendants of a common ancestor
Paraphyletic taxa include some, but not all, descendants of a common ancestor
Polyphyletic taxa includes members with more than one recent common ancestor
Outgroup a lineage closely related to the focal group
The problem of homoplastic traits
traits that appear similar but are not related through ancestry
Convergent evolution- independent evolution of similar traits due
to similar selection pressure (e.g. wings in birds and bats)
Parallel evolution- independent evolution of common traits in
organisms sharing distant relatives (e.g. patterns of butterfly
wings).
Evolutionary reversals- the loss of a derived trait (e.g. limbs of
snakes, teeth of frogs).
Traits used in phylogenetics
Morphology and developmental
the importance of fossils
Molecular
Protein sequences
Genetic markers
DNA sequences
The advantages of molecular traits
1/ They directly reflect the underlying process of evolution- changes
in the hereditary material
2/ There are a vast number of potential traits
3/ They can detect difference between very closely related organism
(even those that show no phenotypic difference)
4/ They are not effected by the environment (unlike some
morphological traits)
5/ Since mutations generally occur as random events with specific
probabilities, the number of mutations can be used to calibrate
evolutionary time (molecular clocks)
Disadvantages ?
Transitions and Transversions in nucleotide
substitutions
Transitions replace a purine base with the other purine base, or a
pyrimidine base with the other pyrimidine base
Pyrimidines
Purines
TC CT
AG G A
Transversions replace a purine with a
pyrimidine or vice versa
A
G Transition
Transversion
TA TG CA C G
AT A C GT G C
C
Transition mutations are about 2 x more common than
transversions
T Transition
Mutation in Coding vs Noncoding DNA
A substantial part of the DNA of eukaryotes is noncoding- introns,
repetitive sequences, pseudogenes
Mutations in noncoding DNA do not generally effect phenotype
and therefore are not subjected to selection
Some mutations in coding regions do not change amino acid
sequence because of the degenerate codon system
Some mutations in coding regions change amino acid sequence to
a similar type of amino acid, therefore having little or no effect on
protein function
Substitutions in Coding regions
Synonymous vs nonsynonymous substitutions
Synonymous substitutions are those that do not change the amino
acid that is specified by the gene
CUU ----> CUC = Leucine -----> Leucine
Nonsynonymous substitutions are those that change the amino
acid chain specified
There are various degrees of nonsynonymous mutations depending
on there effect on protein function. When the mutation changes the
amino acid to a similar type then function may be little effected.
Some amino acids of proteins are more important than othersactive sites for example.
CUU ----> AUU = Leucine -----> Isoleucine
Substitutions in Coding regions
Miss-sense substitutions
Miss-sense substitutions are those that prematurely terminate the
gene
UAU ----> UAG = Tyrosine -----> Stop
UUA ----> UAA = Leucine -----> Stop
Generally rare since nearly always involved change in protein activity
Codon usage
Second Letter
U
First Letter
C
A
G
U
UUU
UUC
UUA
UUG
CUU
CUC
CUA
CUG
AUU
AUC
AUA
AUG
GUU
GUC
GUA
GUG
PhenylalanineF
LeucineL
LeucineL
IsoleucineI
MethionineM
ValineV
C
UCU
UCC
UCA
UCG
CCU
CCC
CCA
CCG
ACU
ACC
ACA
ACG
GCU
GCC
GCA
GCG
SerineS
ProlineP
ThreonineT
AlanineA
A
UAU
UAC
UAA
UAG
CAU
CAC
CAA
CAG
AAU
AAC
AAA
AAG
GAU
GAC
GAA
GAG
TyrosineY
Stop
HistidineH
GlutamineQ
AsparagineN
LysineK
Aspatic
acidD
Glutamic
acidE
G
UGU
UGC
UGA
UGG
CGU
CGC
CGA
CGG
AGU
AGC
AGA
AGG
GGU
GGC
GGA
GGG
CystineC
Stop
TryptophanW
ArginineR
SerineS
ArginineR
GlycineG
to
ne
3
10
In
su
lin
m
yo
gl
ob
in
al
bu
in
m
te
in
ap
r
l
eu
ol
ip
ki
op
n
ro
1
te
in
in
Ate
1
rfe
ro
n
B1
re
la
xi
n
hi
s
Substitutions per site per
1000,000,000 years
Synonymous mutations are more commonly fixed in evolution
12
Synonymous mutations
Nonsynonymous mutations
8
6
4
2
0
Substitutions per site per
1000,000,000 years
7
6
5
4
3
2
1
0
8
9
10
Animal mtDNA
Pseudogenes
Introns
Fourfold degenerate sites
Twofold degenerate sites
Non-degenerate sites
Downstream regions
Upstream regions
Different types of sequence evolve at different rates
Comparing amino acid sequences
Sequence 1
Sequence 2
leu arg phe cys ser ser arg
Sequence 1
Sequence 2
leu arg phe cys ser ser arg
Sequence 1
Sequence 2
Sequence 3
Sequence 4
Sequence 5
Sequence 6
leu
leu
leu
leu
leu
leu
leu phe cys ser ser arg
leu gap phe cys ser ser arg
arg
gap
gap
arg
arg
arg
phe cys ser ser
phe cys ser phe
phe cys ser phe
ile cys ser ser
ile cys ala ser
phe cys ile ser
arg
arg
arg
arg
arg
arg
Comparing amino acid sequences
Sequence 1
Sequence 2
Sequence 3
Sequence 4
Sequence 5
Sequence 6
leu
leu
leu
leu
leu
leu
arg
gap
gap
arg
arg
arg
phe cys ser ser
phe cys ser phe
phe cys ser phe
ile cys ser ser
ile cys ala ser
phe cys ile ser
arg
arg
arg
arg
arg
arg
Sequence Number
1
1
Similarities
2
3
4
5
6
2
2
1
2
1
0
3
4
3
3
4
3
1
2
2
5
3
5
7
4
6
4
4
5
5
3
3
6
6
6
4
4
5
2
5
Differences
Cytochrome C- a highly conserved gene
Acidic side chains
Hydrophobic side
chains
Basic side chains
Human/chimp
Rhesus monkey
Horse
Donkey
Cow
Dog
Rabbit
Gray whale
Grey kangaroo
G
G
G
G
G
G
G
G
G
D
D
D
D
D
D
D
D
D
V
V
V
V
V
V
V
V
V
E
E
E
E
E
E
E
E
E
K
K
K
K
K
K
K
K
K
G
G
G
G
G
G
G
G
G
K
K
K
K
K
K
K
K
K
K
K
K
K
K
K
K
K
K
I
I
I
I
I
I
I
I
I
F
F
F
F
F
F
F
F
F
I
I
V
V
V
V
V
V
V
M
M
Q
Q
Q
Q
Q
Q
Q
K
K
K
K
K
K
K
K
K
C
C
C
C
C
C
C
C
C
S
S
A
A
A
A
A
A
A
Q
Q
Q
Q
Q
Q
Q
Q
Q
C
C
C
C
C
C
C
C
C
H
H
H
H
H
H
H
H
H
T
T
T
T
T
T
T
T
T
V
V
V
V
V
V
V
V
V
E
E
E
E
E
E
E
E
E
K
K
K
K
K
K
K
K
K
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
K
K
K
K
K
K
K
K
K
H
H
H
H
H
H
H
H
H
K
K
K
K
K
K
K
K
K
T
T
T
T
T
T
T
T
T
G
G
G
G
G
G
G
G
G
P
P
P
P
P
P
P
P
P
N
N
N
N
N
N
N
N
N
L
L
L
L
L
L
L
L
L
G
G
G
G
G
G
G
G
G
L
L
L
L
L
L
L
L
L
F
F
F
F
F
F
F
F
F
G
G
G
G
G
G
G
G
G
R
R
R
R
R
R
R
R
R
K
K
K
K
K
K
K
K
K
T
T
T
T
T
T
T
T
T
G
G
G
G
G
G
G
G
G
Q
Q
Q
Q
Q
Q
Q
Q
Q
A
A
A
A
A
A
A
A
A
P
P
P
P
P
P
V
V
P
G
G
G
G
G
G
G
G
G
Y
Y
F
F
F
F
F
F
F
S
S
T
S
S
S
S
S
T
Y
Y
Y
Y
Y
Y
Y
Y
Y
Chicken
Pigeon
Duck
Turtle
Snake
Frog
Tuna
Dogfish
G
G
G
G
G
G
G
G
D
D
D
D
D
D
D
D
I
I
V
V
V
V
V
V
E
E
E
E
E
E
A
E
K
K
K
K
K
K
K
K
G
G
G
G
G
G
G
G
K
K
K
K
K
K
K
K
K
K
K
K
K
K
K
K
I
I
I
I
I
I
T
V
F
F
F
F
F
F
F
F
V
V
V
V
T
V
V
V
Q
Q
Q
Q
M
Q
Q
Q
K
K
K
K
K
K
K
K
C
C
C
C
C
C
C
C
S
S
S
A
S
A
A
A
Q
Q
Q
Q
Q
Q
Q
Q
C
C
C
C
C
C
C
C
H
H
H
H
H
H
H
H
T
T
T
T
T
T
T
T
V
V
V
V
V
C
V
V
E
E
E
E
E
E
E
E
K
K
K
K
K
K
N
N
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
G
K
K
K
K
K
K
K
K
H
H
H
H
H
H
H
H
K
K
K
K
K
K
K
K
T
T
T
T
T
V
V
T
G
G
G
G
G
G
G
G
P
P
P
P
P
P
P
P
N
N
N
N
N
N
N
N
L H G
L H G
L H G
L N G
L H G
L Y G
L W G
L S G
L
L
L
L
L
L
L
L
F
F
F
I
F
I
F
F
G
G
G
G
G
G
G
G
R
R
R
R
R
R
R
R
K
K
K
K
K
K
K
K
T
T
T
T
T
T
T
T
G
G
G
G
G
G
G
G
Q
Q
Q
Q
Q
Q
Q
Q
A
A
A
A
A
A
A
A
E
E
E
E
V
A
E
Q
G
G
G
G
G
G
G
G
F
F
F
F
Y
F
Y
F
S
S
S
S
S
S
S
S
Y
Y
Y
Y
Y
Y
Y
Y
Samia moth
G
Hornworm moth
G
Screw worm fly
G
Fruit fly
G
Bakers yeast
G
Candida k rusei (yeast) G
Neursopora (mold) G
Wheat
G
Sunflower
G
Mung bean
G
Rice
G
Sesame
G
N
N
D
D
S
S
D
N
D
D
N
D
A
A
V
V
A
A
S
P
P
S
P
V
E
D
E
E
K
K
K
D
T
K
K
K
N
N
K
K
K
K
K
A
T
S
A
S
G
G
G
G
G
G
G
G
G
G
G
G
K
K
K
K
A
A
A
A
A
E
E
E
K
K
K
K
T
T
N
K
K
K
K
K
I
I
I
L
L
L
L
I
I
I
I
I
F
F
F
F
F
F
F
F
F
F
F
F
V
V
V
V
K
K
K
K
K
K
K
K
Q
Q
Q
Q
T
T
T
T
T
T
T
T
R
R
R
R
R
R
R
K
K
K
K
K
C
C
C
C
C
C
C
C
C
C
C
C
A
A
A
A
E
A
A
A
A
A
A
A
Q
Q
Q
Q
L
E
E
Q
Q
Q
Q
Q
C
C
C
C
C
C
C
C
C
C
C
C
H
H
H
H
H
H
H
H
H
H
H
H
T
T
T
T
T
T
V
V
V
V
V
V
E
V
V
V
V
V
E
E
E
E
E
E
A
A
A
A
K
A
E
E
E
E
E
A
K
K
K
K
G
G
G
G
G
G
N
G
G
G
G
G
G
G
G
G
G
G
L
A
A
A
A
A
K H
K H
K H
K H
P H
P H
T Q
H
H
H
H
H
K
K
K
K
K
K
K
K
K
K
K
K
V
V
V
V
V
V
I
Q
Q
Q
Q
Q
G
G
G
G
G
G
G
G
G
G
G
G
P
P
P
P
P
P
P
P
P
P
P
P
N
N
N
N
N
N
A
N
N
N
N
N
L
L
L
L
L
L
L
L
L
L
L
L
F
F
L
L
I
I
L
L
L
L
L
L
Y
F
F
I
F
F
F
F
F
F
F
F
G
G
G
G
G
G
G
G
G
G
G
G
R
R
R
R
R
R
R
R
R
R
R
R
K
K
K
K
H
H
K
Q
Q
Q
Q
Q
T
T
T
T
S
S
T
S
S
S
S
S
G
G
G
G
G
G
G
G
G
G
G
G
Q
Q
Q
Q
Q
Q
Q
S
T
T
T
T
A
A
A
A
A
A
A
T
T
T
T
T
P
P
A
A
P
P
D
A
A
A
P
P
G
G
G
G
G
G
G
G
G
G
G
G
F
F
F
F
Y
Y
Y
Y
Y
Y
Y
Y
S
S
A
A
S
S
A
S
S
S
S
S
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
Y
T
T
T
T
T
H
H
H
H
H
H
H
H
N
H
H
H
H
H
H
H
H
N
N
N
N
G
G
G
G
G
G
G
G
G
G
G
G
Amino acid substitutions
(per 100 residues) in cytochrome c
A molecular clock for Cytochrome c
60
Angiosperms vs animals
50
Insects vs vertebrates
40
Yeast vs mould
Mammals
vs reptiles
30
Birds vs
reptiles
20
Fish vs land vertebrates
Amphibians vs birds and mammals
10
Birds vs mammals
0
0
200
400
600
800
1000
1200
Time since divergence (millions of years)
The Neutral Theory of molecular evolution
Most mutations are either selectively neutral or nearly so.
Thus, the genetic variation within species results from random
genetic drift
Consider population of size N with a neutral mutation rate at a locus
of  mutations per gamete per generation
No. of new mutations =  x 2N
Probability of fixation by genetic drift = frequency, p = 1/2N
Number of new mutations per generation that are likely to become
fixed by genetic drift = no. of mutations x probability of fixation
=
Molecular clocks
The rate of fixation of neutral mutations is equal to the neutral
mutation rate
Thus, sequences diverge in evolution at a constant rate
Thus, the divergence between two sequences can be used to say
when the two organisms diverged from each other
But remember
•Not all mutations are neutral
•Not all loci change at the same rate
•Transitions are more common than transversions
•Rates are strictly based on generations (not years), and
reproductive rates vary between species
Therefore, all molecular clocks need calibrating
Calibration of -globin molecular clock
Divergence of humans from other species based on -globin
molecular clock calibrated on fossil evidence of divergence
600
Shark
from cows
500
Frog
400
Chicken
Alligator
300
200
Cow
Quoll
Million years
ago
Carp
100
Baboon
0
Species
Divergence based on molecular clock
Divergence based on fossil record