Genes and Evolution 2025
Lecture 1:
1. Evolution
2. Phenotypic Variation
3. Genetic Variation
4. Mutation
The genome contains an organism's the
complete set of instructions for
development, survival and reproduction
CATCATCATCAT
The genome contains an organism's the
complete set of instructions for
development, survival and reproduction
Genetic variation encodes
the differences
among organisms
A single allele in IGF1 (insulin growth factor 1)
determines small body size in dogs
Sutter et al (2007) Science
small CCGCAAGAGGGTCCTATGCT
dogs CCGCAAGAGGGTCCTATGCT
big CCGCAGGAGGGTCCTATGCT
dogs CCGCAGGAGGGTCCTATGCT
CATCATCATCAT
Genetics enables us to quantify, test and measure the basis of evolution
(and rule out incorrect hypotheses)
To distinguish between
alternative explanations:
• Formulate expectations
• Quantify genetic variation
• Measure, calculate & test
Species are not static, but change through time
What processes underlie this change through time?
Species are not static, but change through time
What processes underlie this change through time?
Two possibilities:
1. Transformational change (things morph through time, e.g. Lamarckism)
Ancestral giraffes stretched their necks
Their offspring inherited stretched necks
Species are not static, but change through time
What processes underlie this change through time?
Two possibilities:
1. Transformational change (things morph through time, e.g. Lamarckism)
Ancestral giraffes stretched their necks
Their offspring inherited stretched necks
2. Variational change (descent with modification, e.g. Darwinism)
Ancestral giraffes varied in neck length
Long-necked giraffes survived and passed
on genes to offspring
Darwinian Evolution – i. species evolve via descent with modification over long evolutionary
time scales
f
m F
q
p
b
o
c
XIV
a14
14
14
14
14
14
14 14
14
XIII
XII
XI
f10
a10
a9
f9
k8
a8
a7
l7
k7
f6
a6
d5
a5
d4
a4
l8
m9
IX
m8
VIII
m7
VII
m6
VI
k5
m5
V
m4
i3
s2
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X
k6
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a2
l7
m10 E10 F10
IV
m3
III
m2
II
m1
A B
I
C
D
E F
“... we have only to suppose the steps in the
process of modification to be more
numerous or greater in amount, to convert
these three forms into well-defined species”
Darwin, (1859) Origin of Species, 2nd Edition. p.120
G H
ICharles
K L Darwin
a14
q14
p14
Darwinian Evolution – ii. natural selection favors beneficial traits
generations
f
m F passed on to subsequent
o
c
XIV
14
b14
14
14 14
14
XIII
XII
XI
f10
a10
a9
f9
k8
a8
a7
l7
k7
f6
a6
d5
a5
d4
a4
l8
m9
IX
m8
VIII
m7
VII
m6
VI
k5
m5
V
m4
i3
s2
a1
X
k6
i4
a3
a2
l7
m10 E10 F10
IV
m3
III
m2
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A B
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C
Alfred R Wallace
D
E F
“... we have only to suppose the steps in the
process of modification to be more
numerous or greater in amount, to convert
these three forms into well-defined species”
Darwin, (1859) Origin of Species, 2nd Edition. p.120
G H
ICharles
K L Darwin
“…this new, improved, …race might …give rise to new
varieties, exhibiting several diverging modifications, any of
which, tending to increase the facilities for preserving
existence, must, by the same general law, in their turn
become predominant. ”
Wallace (1858) On the Tendency of Varieties to depart indefinitely
from the Original Type. (2009). Alfred Russel Wallace Classic
Writings. Paper 1.
Evidence for “modification with descent”
Herron & Freeman - chapter 2 (also discussed later in course)
Evidence for “evolution by natural selection”
(we discuss in detail this week)
‘typica’ – lower fitness at polluted sites
‘carbonaria’ – high fitness at polluted sites
Biston betularia, Peppered moth. Wikimedia, CC.
The mechanisms of evolutionary change
The mere recognition of a pattern does not constitute a scientific study
If we claim to understand the evolution of a trait or of the diversity of species, we must
not only explain what happened but also the mechanisms responsible
Studying the mechanisms of evolutionary change requires the
inclusion of genetics and heredity
Darwin didn’t know the mechanism of “descent with modification”
At the time, “Blending inheritance"
was assumed. (ie. characters of both
parents were mixed in offspring)
Spikiness & color mixed in offspring
Darwin didn’t know the mechanism of “descent with modification”
At the time, “Blending inheritance"
was assumed. (ie. characters of both
parents were mixed in offspring)
But around the same time,
Mendel was busy studying
peas
Gregor Mendel, 1822-1884
Spikiness & color mixed in offspring
Mendel showed that traits (characters)
are inherited independently of one another
At the time, “Blending inheritance"
was assumed. (ie. characters of both
parents were mixed in offspring)
But around the same time,
Mendel was busy studying
peas
Gregor Mendel, 1822-1884
Mendel’s laws of inheritance:
1. Law of segregation (diploid alleles separate in gametes)
Spikiness & color mixed in offspring
2. Law of independent assortment (alleles of different genes separate
independently of one another)
3. Law of dominance (when two alleles at a locus are present, the
dominant allele can mask the effects of the weaker allele)
Mendel’s work laid the foundation for modern genetics
Gregor Mendel,
1822-1884
He chose seven traits to study:
They all happened to be controlled by single/few genes with alleles of large effect. (notable
segregation of phenotypes in progeny)
The genes all happened to be unlinked (on different chromosome) - clear patterns of trait
independence in progeny
But, others showed that many traits are continuous (not discrete),
and influenced by the environment…
How to reconcile evolutionary mechanism that fits both
”Mendelian” discrete traits with independent assortment
and continuous traits with quantitative variation?
The Evolutionary “Modern Synthesis”
Action of numerous genetic and environmental factors gives
continuous distribution in traits
Natural selection can lead to changes in allelic frequencies
Small populations subject to stochasticity “genetic drift”
Species are reproductively isolated groups of organisms
Key contributors:
Ronald Fisher
Sewall Wright
JBS Haldane
Theodosius Dobzhansky
Ernst Mayr
…and many others
Theory of adaptive evolution by natural selection
after the Modern Synthesis
The reformulation of Darwin’s postulates:
1. Individuals vary as a result of mutations
2. Individuals pass on their alleles to their offspring
3. In every generation, some individuals are more successful at surviving and reproducing than others
4. The most successful individuals are (not a random subset of the population, but) those with alleles
and allelic combinations that best adapt them to their environment
The outcome is that alleles associated with higher fitness
increase in frequency over generations ➔ adaptive evolution
What is evolution?
Genetic variation is the raw material for evolution
It can be quantified and studied to identify evolutionary patterns and to test
hypotheses on evolution and evolutionary processes
Evolution is the changes in allele frequencies over time
By natural selection: individuals carrying particular alleles do better
Random and other processes may also lead to evolution
We can use DNA to study evolution,
and evolution to study how DNA functions
The information we extract from DNA connects variation in individual genomes to:
phenotypes
population-level processes, and
the generation of biodiversity
It allows us to reach back in time and test hypotheses on individuals, traits, populations, species!
In ecology and evolution DNA is used to:
• identify species, families (paternity),
populations, diets
• track organisms through time & space
• reconstruct evolution of adaptations,
ancestors, phylogenies, species origins and
extinctions, body plans
In genetics and developmental biology
evolution is used to:
• identify functional parts of the genome
• connect genotype to phenotype
• dissect how molecular processes and
pathways work.
Mutations are essential for evolution, but not all mutations are good or bad
Mutation creates differences (variants) among individuals
Mutations can be lost or inherited by offspring
DNA is copied and passed from
generation to generation
(including DNA variants)
50% of a parent’s genome
is passed on to offspring
Mutations are essential for evolution, but not all mutations are good or bad
Mutation creates differences (variants) among individuals
Mutations can be lost or inherited by offspring
DNA is copied and passed from
generation to generation
(including DNA variants)
50% of a parent’s genome
is passed on to offspring
Mutations arise continuously,
but most are somatic (not germline),
and DNA repair mechanism are very
good.
Few are passed on to next
generation through the germline
(gametes)
Mutations arise continually, but the genome is big and mutation rates are very low
How many mutational differences between any two humans?
4-6M differences out of 3billion positions
0.01%
Natural selection acts on individual variation,
but evolutionary consequences occur in populations
Individuals
Populations
Individuals differ
(both in phenotype & genotype)
Populations can differ
(in phenotypic and genetic composition)
Natural selection acts on the individual
phenotype
Populations are not the target
of natural selection
Individuals do not evolve
Evolution can be observed at the level of
populations.
Any changes to their phenotype are NOT passed on to
their offspring
(It is a change in the frequency of an allele in the
population over time)
Changes in the frequencies of genetic variation over time = Evolution
Frequencies may change:
through natural selection when a DNA sequence
variant is either beneficial or deleterious
(differential survival, reproductive output)
Through random processes, such as chance
events (“drift”)
due to migration
non-random mating
or mutation of a new allele
Changes in the frequencies of genetic variation over time = Evolution
Frequencies may change:
A C
G
through natural selection when a DNA sequence
variant is either beneficial or deleterious
(differential survival, reproductive output)
several
generations
10s to >>10000s
Through random processes, such as chance
events (“drift”)
due to migration
non-random mating
or mutation of a new allele
Frequency of variant in
geneX in an ancestral
population
Mutation
New T allele arises
Natural Selection
favors C allele
Drift
random changes
GA
C
A C
G
TC
A
G
Not all evolution is adaptive or occurs by natural selection !
Evolution by natural selection is a non-random process
Populations become better adapted to their environment
Random and other processes may also lead to changes in allele frequencies ( = evolution)
Mutation
Chance events (genetic drift)
Migration
Non-random mating
Different processes operate simultaneously, but they may differ in strength and importance
A window back in time: by studying present day DNA variation,
we can reconstruct the past (ancestral coalescence)
Full geneology
DNA is copied and passed from
generation to generation
(including DNA variants)
Ancestry of
extant lineages
Ancestry of
sampled lineages
Coalescent tree of
sampled lineages
The shape of genealogy reflects population history
Different evolutionary and demographic
processes lead to different patterns of change in
allele frequency
Stable population
Expanding population Shrinking population
Evolution = change over time (generations)
Five key processes influencing evolution
Mutation
Migration & Gene Flow
Non-random mating
Drift & Bottlenecks
(small population size)
Adaptation & Selection
HWE
(null model)
Five Fingers of Evolution, Paul Anderson
https://www.youtube.com/watch?v=5NdMnlt2keE
Fundamental principles of evolutionary change
Individuals differ from one another
Today
Genetic variation arises by random mutation and recombination
Today
The proportions of alleles and genotypes within a population change over time
Tuesday
Such changes in the proportions of genotypes may occur either by nonrandom,
consistent differences among genotypes in survival or reproduction rates (natural
selection) or by random fluctuations (genetic drift)
Wednesday, Thursday,
Friday
As a result of different histories of genetic drift, gene flow and natural selection,
populations of a species may diverge
New taxa arise from prolonged, gradual evolution & all species form a great tree of
life (phylogeny)
The molecular basis of traits and adaptation affect their evolution (multiple loci,
genomes)
Week 2: Monday,
Wednesday
Week 2: Thursday &
Friday
Week2: Tuesday
& Week 3: Monday
Pause
ii. Phenotypic Variation
Both genes and the environment influence an organisms’ phenotype
Phenotype - an observable characteristic of an organism
may be external (e.g. morphology, behaviour) or internal (e.g. physiology)
Phenotypic Variation
Both genes and the environment influence an organisms’ phenotype
Phenotype - an observable characteristic of an organism
may be external (e.g. morphology, behaviour) or internal (e.g. physiology)
P
~
G
Phenotype
~
genotype
(trait)
(allelic variant)
+
+
E
environment
+
+
(conditions during life)
(G x E)
gene x environment
(interactions)
What does this formula mean?
P
~
G
Phenotype
~
genotype
(trait)
+
+
An individuals
Genotype
+
environment
(allelic variant)
Variation in phenotype
E
12.0
6.0
16.5
1.8
GG
GC
GG
CC
+
gene x environment
(conditions during life)
+
the environment
an individual has
experienced
“is dependent on,
can be predicted by, or
can be explained by”
Ind1
Ind2
Ind3
Ind4
(G x E)
10℃
10℃
25℃
25℃
(interactions)
+
an interaction term that
modifies the environmental
effect in some genotypes
Bigger
Smaller
Bigger
Smaller
What does this formula mean?
phenotypic
variation
explained heritable
by
variation
P
~
G
Phenotype
~
genotype
(trait)
(allelic variant)
+
+
not heritable
variation
+
heritable
variation
+
E
+
(G x E)
environment
+
(conditions during life)
gene x environment
(interactions)
P
~
G
Phenotype
~
genotype
(trait)
Variation in phenotype
Ind1
Ind2
Ind3
Ind4
12.0
6.0
16.5
1.8
(allelic variant)
An individuals
Genotype
GG 2
GC 1
GG 2
CC 0
Phenotypic score
The genetic basis of a phenotype is often modelled
using a simple regression
eg Genome Wide Association Studies (GWAS)
Recode the genotype
as number of G alleles
0,1 or 2
A linear regression
P ~ β0 + β1*genotype + ε
0
1
2
CC
GC
GG
How many copies of G allele?
P
~
G
Phenotype
~
genotype
(trait)
Variation in phenotype
Ind1
Ind2
Ind3
Ind4
12.0
6.0
16.5
1.8
(allelic variant)
An individuals
genotype
GG
GC
GG
CC
Phenotypic score
But there are some assumptions to keep in mind
(e.g. additivity)
A linear regression assumes
the allelic effect is additive
(phenotype of GC
heterozygotes is midway
A linear regression between phenotype of CC & GG
homozygotes)
P ~ β0 + β1*genotype + ε
0
1
2
CC
GC
GG
How many copies of G allele?
~
G
Phenotype
~
genotype
(trait)
(allelic variant)
Phenotypic score
P
G allele is
dominant over C
The mode of inheritance may not be additive.
A heterozygote may resemble one of the homozygote classes
(ie. the allele may be dominant or recessive)
0
1
2
CC
GC
GG
How many copies of G allele?
P
~
G
Phenotype
~
genotype
(trait)
(allelic variant)
Phenotypic score
The mode of inheritance may not be additive.
A heterozygote may resemble one of the homozygote classes
(ie. the allele may be dominant or recessive)
G allele is
recessive to C
0
1
2
CC
GC
GG
How many copies of G allele?
How much of trait variation has a genetic component?
(using parent-offspring regression to estimate heritability)
Offspring trait value
Heritability (h2):
the amount of the variation in a trait that can be attributed to genetic variation
Parents’ trait mean
How much of trait variation has a genetic component?
(using parent-offspring regression to estimate heritability)
Offspring trait value
Heritability (h2):
the amount of the variation in a trait that can be attributed to genetic variation
h2=0.90
(again only considers additivity of alleles).
We refer to this as the “narrow-sense
Heritability”.
“Broad-sense heritability” refers to trait
variance explained by all of these:
additivity
+ dominance
+ epistasis
Parents’ trait mean
G: An individuals’ phenotype may be controlled by few or many genes
that vary within a species (polymorphisms)
Red / green color blindness
(protonopia / deuteronopia)
OPN1LW/OPN1MW genes
Height
many loci across the genome,
each of small effect size
Coloration in Geese
single locus, two allelic variants
Sexual dimorphism in wing
pattern mimicry in butterflies
few loci of large effect size
A small experiment:
measuring phenotypic variation in Genes & Evolution students!
Can you taste Phenylthiocarbamide (PTC?)
A.
Yes, awful!
B.
Yes, somewhat
C.
Yes, tastes good
D. No, I don’t taste anything
(just soggy paper)
What is Phenylthiocarbamide (PTC)?
A synthetic chemical used specifically to study variation in human taste
Phenylthiocarbamide
The ability to taste PTC depends on the alleles you carry at the TAS2R38
taste receptor gene (chromosome 7).
Genotypes at TAS2R38 explain 75% variation in PTC sensitivity
There are two frequent haplotypes (alleles), and 3 rare ones
“classical” taster allele (PAV) and non-taster allele (AVI) carry DNA
mutations in 3 codons causing differences inTAS2R38 protein structure.
TAS2R38: A gene encoding a bitter
taste receptor
Humans populations have genetic variation in the ability to taste PTC
• Polymorphism is (mostly) due to
variation at a single locus
Woodings 2006 Genetics
Can you taste Phenylthiocarbamide (PTC?)
Phenotypic Variation
Both genes and the environment influence an organisms’ phenotype
not heritable
phenotypic variation
phenotypic
variation
P
~
G
Phenotype
~
genotype
(trait)
heritable
variation
explained heritable
by
variation
(allelic variant)
+
+
E
environment
+
+
(conditions during life)
(G x E)
gene x environment
(interactions)
E: Environment may also influence an individual’s phenotype
(”Phenotypic plasticity”: the ability of a single genotype to produce different phenotypes under different
environmental conditions
Sunburn in humans
(extent of sunburn depends on
amount of sun exposure)
Calluses and blisters
(extent of callus/blister depends on
degree of mechanical stress)
E: Environment may also influence an individual’s phenotype
(”Phenotypic plasticity”: the ability of a single genotype to produce different phenotypes under different
environmental conditions
Wingless vs winged aphids
in response to crowding on host plant
(same genotypes grow wings when crowded)
Helmets vs no-helmets in daphnia (water fleas)
in response predator cues
(same genotypes, grow helmets in presence of
predators
Phenotypic Variation
Both genes and the environment influence an organisms’ phenotype
phenotypic
variation
P
~
G
Phenotype
~
genotype
(trait)
(allelic variant)
heritable
variation
not heritable
variation
explained heritable
by
variation
+
+
E
environment
+
+
(conditions during life)
(G x E)
gene x environment
(interactions)
G x E: Gene by environment interactions
The effect of genotype on an organism’s phenotype depends on the environment
(or equivalently, the effect of the environment on an organisms phenotype depends on the genotype)
Mean number of bristles
This is common! One classic example:
Reaction norm:
the pattern of phenotypic plasticity
exhibited by a genotype
Temperature
Genes + Env (no interaction)
G1
G2
E1
E1
E2
E2
G1=Genotype 1; G2=genotype 2; E1=Environment1; E2=Environment2
G1
Phenotype / Trait
G1
G2
Genes only
Phenotype / Trait
Environment only
Phenotype / Trait
“main effects”
(no interactions here)
G x E Reaction Norms can have many different shapes
G2
E1
E2
Genes + Env (no interaction)
G1
G2
E1
E1
E2
E2
G1=Genotype 1; G2=genotype 2; E1=Environment1; E2=Environment2
G1
G2
E1
E2
Phenotype / Trait
Genes x Env
E1
E2
Genes x Env
G1
G2
E1
G2
E2
Phenotype / Trait
Genes x Env
G1
Phenotype / Trait
Phenotype / Trait
G1
G2
Genes only
Phenotype / Trait
Environment only
Phenotype / Trait
GxE interactions
(reaction norms)
“main effects”
(no interactions here)
G x E Reaction Norms can have many different shapes
G1
G2
E1
E2
Plasticity variation with a genetic basis (ie G x E) can evolve!
Phenotypic plasticity can be adaptive
- Use cues to estimate (future) environmental condition
- React or anticipate: adjust phenotype accordingly to increase fitness
Plasticity variation with a genetic basis (ie G x E) can evolve!
Phenotypic plasticity can be adaptive
- Use cues to estimate (future) environmental condition
- React or anticipate: adjust phenotype accordingly to increase fitness
When do you expect the degree of plasticity to become target of
selection (i.e. a change in the reaction norm)?
When cues and/or environmental conditions and/or optimal phenotype
change, e.g. egg-laying date under changing climate
What role does plasticity play in evolution?
Two competing schools of thought:
What role does plasticity play in evolution?
Two competing schools of thought:
1. Plasticity “buffers” or “constrains” adaptive evolution
(it dampens response to selection by obscuring the beneficial heritable genotype)
‘Plasticity “hides” the true phenotypic “read-out” of a genotype’
Phenotype / Trait
(Blue-ness)
Genes x Env
G1 (bb)
G2 (BB)
E1
E2
What role does plasticity play in evolution?
Two competing schools of thought:
1. Plasticity “buffers” or “constrains” adaptive evolution
(it dampens response to selection by obscuring the beneficial heritable genotype)
‘Plasticity “hides” the true phenotypic “read-out” of a genotype’
2. Plasticity facilitates adaptive evolution
(when the environment changes, one part ot the plastic response may be favored
enabling the population to persist and further variation be selected).
Phenotype / Trait
(Blue-ness)
Genes x Env
G1 (bb)
G2 (BB)
E1
E2
Only some parts of plasticity’s role in evolution are controversial
In theory selection may favor any trait,
when the variation in that trait has a heritable genetic basis
Some evidence from Dutch birds…
But rates of adaptation / selection may still be
constrained / inefficient
Science, 2005
Pause
Part 3
iii.
Genetic
Variation
Genetic Variation!
How much genetic variation is there?
among individuals?
among populations?
among species?
How much genetic variation in natural populations?
What type? How is it maintained?
Three schools of thought in population genetics:
Classical
Populations are uniform
Only one optimal wildtype
genotype
Natural selection is mostly
“purifying” (removes / purges rare
deleterious mutations)
Fisher, Muller
How much genetic variation in natural populations?
What type? How is it maintained?
Three schools of thought in population genetics:
Classical
Balancing (selectionist)
Populations are uniform
Polymorhpisms are common
Only one optimal wildtype
genotype
Balancing selection maintains
heterozygosity
Natural selection is mostly
“purifying” (removes / purges rare
deleterious mutations)
Selection is more important then
drift in determining allele
frequencies in a population
Fisher, Muller
Dobzhansky
How much genetic variation in natural populations?
What type? How is it maintained?
Three schools of thought in population genetics:
Classical
Balancing (selectionist)
Neutral
Populations are uniform
Polymorhpisms are common
Most alleles are neutral in fitness
effects
Only one optimal wildtype
genotype
Balancing selection maintains
heterozygosity
Polymorphisms maintained by
mutation + drift
Natural selection is mostly
“purifying” (removes / purges rare
deleterious mutations)
Selection is more important then
drift in determining allele
frequencies in a population
Drift is more important than
selection in determining allele
frequencies
Fisher, Muller
Dobzhansky
Kimura, Lewontin
How much genetic variation in natural populations?
What type? How is it maintained?
Three schools of thought in population genetics:
Classical
Balancing (selectionist)
“Nearly” Neutral
Populations are uniform
Polymorhpisms are common
Too few polymorphisms! Most
alleles are “nearly” neutral or
slightly deleterious in fitness
effects
Only one optimal wildtype
genotype
Balancing selection maintains
heterozygosity
Polymorphisms maintained by
mutation + drift + weak purifying
selection removing slightly
deleterious mutations
Natural selection is mostly
“purifying” (removes / purges rare
deleterious mutations)
Selection is more important than
drift in determining allele
frequencies in a population
Drift is important but purifying
selection may matter, especially in
large populations.
Fisher, Muller
Dobzhansky
Kimura, Lewontin, Ohta
Experiments suggest that on average mutations are slightly deleterious…
Evolve a virus over many generations, let it accumulate new mutations.
Compare the effect of new mutations on fitness relative to ancestral strain fitness
Many neutral
Quite a few lethal!
A number deleterious
Few mutations
are beneficial
Fitness relative to ancestor
But mutations also lead to adaptation
(the rare beneficial mutations spread through the population)
Fitness at the end of
the experiment
is higher than the
original ancestor
How do we measure and quantify genetic variation?
P = percentage polymorphic sites/loci/genes
# Does not tell us the number of alleles or their
frequencies (might be very rare or very common)
Population/Species 2
Population/Species 1
H = percentage of sites that are heterozygous
# Gives an indication of mutation frequency and
abundance across genome in an individual
Ind1 ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGAACATGGAACTTTATATATATATAGACTTGTCAAT
ACTGGTCTCTCT--CTGGGACGTGGTGAACATAGAACATGGAACTTTATATATATA--GACTTGTCAAT
ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGATCATGGAACTTTATATA------GACTTGTCAAT
Ind2 ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGAACATGGAACTTTATATATA----GACTTGCCAAT
P = 5/70
H = 0.6
Ind2 ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGATCATGGAACTTTATATATATATAGACTTGCCAAT
ACTGGTCTCTCTTTCTGGGACGTGGTGAACATAGAACATGGAACTTTATATA------GACTTGCCAAT
ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGATCATGGAACTTTATATATATATAGACTTGCCAAT
Ind3 ACTGGTCTCTCT--CTGGGACGTGCTGAACATAGATCATGGAACTTTATATATATATAGACTTGCCAAT
ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGATCATGGAACTTTATATATATATAGACTTGCCAAT
Ind4 ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGATCATGGAACTTTATATATATATAGACTTGTCAAT
ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGATCATGGAACTTTATATATATATAGACTTGCCAAT
Ind5 ACTGGTCTCTCTTTCTGGGACGTGCTGAACATAGATCATGGAACTTTATATATATATAGACTTGCCAAT
P = 2/70
H = 0.13
Genetic variation in typical natural populations
Estimates from allozyme electrophoresis for typical
natural populations:
P : 0.33 – 0.50
H : 0.04 – 0.15
Q: Why would more plant species have a very low
heterozygosity ?
Allozyme Heterozygosity Figure 5.25
Variant sites per
genome (millions)
Genetic variation in human populations decreases with distance from Africa
Cheetahs have exceptionally low levels of genetic diversity
Acinonyx jubatus raineyi :
P = 0.04; H = 0.01
Acinonyx jubatus jubatus :
P = 0.02; H = 0.0004
Populations derive from a
very small number of
founders (bottleneck)
The amount of genetic variation in a
species differs
πS = synonymous nucleotide diversity
(amount of ”neutral” differences between
pair of chromosomes sampled)
Romiguier et al Nature (2014)
The amount of genetic variation in a
species differs
πS = synonymous nucleotide diversity
(amount of ”neutral” differences between
pair of chromosomes sampled)
Life history strategies influencing population size are best predictors of
genetic variation.
Drift is a major force determining genetic diversity
(more on Thursday!)
Romiguier et al Nature (2014)
Neutralist – selectionist controversy
How much of genetic variation within a population is adaptive?
The dispute is not on whether some mutations are neutral and others may be
under balancing selection
It is about the relative importance of one type over the other type of selection
The substantial levels of protein variation shows us that much genetic variation
exists in natural populations
The remaining and unanswered question is how much of the genetic variation
that exists in natural populations is adaptive
Big open question with rapidly changing environment!
Pause
iv. Mutation: What is heritable genetic variation?
iv. Mutation: What is heritable genetic variation?
For majority of cases,
genetic material is transmitted across generations in the form of DNA inside gametes
Heritable genetic variation = differences in the nucleotide sequence of DNA that are passed
on to subsequent generations
ATAGATCATGG
ATAGACCATGG
Allele 1
Allele 2
Variation at the DNA sequence level can have functional effects
that influence cell fate / function
DNA
transcription
RNA
translation
Protein
Concepts of Genetics, Figure 1.7
Genetic variation can occur anywhere in the genome
(mutations are random without regard to whether they’ll be harmful or beneficial)
But they may be distributed non-randomly across the genome
due to mutation mechanism (e.g. crossing over occurs non-randomly)
or due to selection (e.g. purifying selection removes individuals with deleterious
mutations so less genetic variation in gene rich regions)
Coding
Stop
‘On’ in limb
‘Off’ in brain
Coding
5’ Untranslated region Start
3’ UTR
Protein Coding Exons
Splice variant
Differences at a given location in the genome are called “alleles”
Homologous chromosomes
ATAGATCATGG
ATAGACCATGG
the “T” allele
the “C” allele
Differences at multiple linked alleles are referred to as “haplotypes”
Homologous chromosomes
ATAGATCATGG
ATAGACCATGG
Haplotype 1
Haplotype 2
The term “genotype” is used to refer to the two alleles carried by an individual at a
single locus: e.g. “T/C heterozygote or CC homozygote”
But it can also be used more broadly, refer to haplotypes or entire genome.
e.g. a genetic strain
The type of difference at a given location depends on the type of mutation
Single Nucleotide
Polymorphisms, “SNPs”
ATAGATCATGG
ATAGACCATGG
Copy Number Variation ATAGAATAGAA
ATAGACCATGG
(CNVs, duplications)
Insertions/deletions,
“indels”
ATAGA---TGG
ATAGACCATGG
Short Tandem Repeats
e.g. “mini/microsatellites”
Short Tandem Repeats
5-mer AGAGAGAGAGA
e.g. “mini/microsatellites” 3-mer AGAGAG—---A
2-copy
1-copy
ATAACTAGTGG
ATAGATCATGG
Different types of mutations are generated by different types of mechanisms
(with different likelihoods/probabilities/frequencies)
Mutagens e.g UV, chemical exposure
DNA double-stranded break
Copying errors during cell division / DNA repair
Replication slippage
Meiotic errors (unequal crossing over)
Chromosomal aneuploidies
Transposable elements (jumping genes)
Meiosis: independent assortment
Recombination! Crossing over creatings novel haplotypes
…
Mutations are random – the likelihood of a mutation occuring does not
depend on whether it has a beneficial effect
Overall, mutations rates are low (e.g. 10-8) and vary across taxa
We are all mutants!
Each human embryo has ~100 new mutations of which ~2 are deleterious
Different mutation rates of different mutation types
makes them useful for studying “recent” or “old” evolutionary change
Category
Approx Rate / Locus or bp
SNP (base substitution) ~10⁻⁸ per base / generation
Microsatellite (fast
motif, many repeats)
~10⁻⁴ to 10⁻² per locus / generation
Coding exons
(under constraint)
~ lower than genomic average (e.g. fewer
tolerated mutations)
Intergenic / nonfunctional / nonconstrained regions
~= or higher than baseline per base, depending
on mutational “hotspots”
Mutations rates can differ across environments
“Effect size” of mutations on phenotypes or fitness
can range from none to drastic
1bp substitution can give resistance to pesticides
Master control genes in development
Fine tuning regulatory changes to transcription
Pleiotropy: a single mutation may affect more than one
character trait
Meiosis and sexual reproduction are
important sources of multilocus genetic variation:
ATAGATGCATCAGGGTGG homolog 1
crossing over X
ATAGATGCACCAGGGTGG homolog 2
ATAGATGCATCAGGGTGG
ATAGATGCATCAGGGTGG
ATAGATGCATCAGGGTGG
parent1
ATAGATGCACCAGGGTGG gametes
fertilization
ATAGATGCACCAGGGTGG diploid offspring
ATAGATGCATCAGGGTGG with novel haplotypes
Take home summary of part iv. mutations
Mutation = alterations in DNA that are subsequently replicated
Different types” From point mutations / SNPs to alterations of segments of chromosomes to
structural re-arrangments
Type and location of mutation matters for its effect
Mutation rate low, but not insignificant
Necessary, but not sufficient, for evolution
Changes in phenotype: from none to drastic
Alters pre-existing biochemical or developmental pathways
Mutations are random not directed: The likelihood that a mutation will occur does not
depend on whether or not it would be advantageous.
90
Take home summary of part i. evolution
Evolution occurs via variational change (descent with modification).
Modern synthesis reconciles different fields of study of genetics, discrete, and continuous traits
building a quantifiable and testable framework to describe evolution in natural populations as as a
change in allele frequencies over time.
Evolution requires heritable variation passed on to subsequent generations.
Evolution is affected by a number of different forces: drift, non-random mating, mutation, migration,
natural selection.
By studying changes in allele frequencies over time, we can quantify the effects of these forces.
Natural selection acts on individual variation, but evolutionary consequences occur in populations
DNA can be used to reconstruct historical relationships (ancestry) using coalescence
Shapes of genealogies can be use to infer changes in demographic history
91
Take home summary of part ii. phenotypic variation
Phenotypic variation may be caused by genes, environment, gene x environment
interactions (or a combination of all three).
The genetic basis of a trait is commonly tested using linear models (regression)
Alternatively the amount of variation in a trait that can be explained by genes, heritability h2,
can be estimated from parent/offspring regression.
Additivity is a typical assumption, yet alleles can also act in a recessive/dominant fashion.
Plasticity described changes in phenotype in response to changes in the environment by a
single genotype. The lack of a heritable component to pure plasticity, makes its role in
evolution questionable.
But the strength/nature/extent of plasticity may vary among individuals and can have a
genetic basis -> gene x environment interactions.
Evidence of plasticity being heritable and responding to selection
But its role in constraining/buffering vs facilitating rates of adaptive evolution is still debated.
92
Take home summary of part iii. genetic variation
Genetic variation in a population can be measured by:
proportion of variable sites, or percentage heterozygous sites (and
diversity)
nucleotide
The amount of genetic variation varies across species, and can be affected by processes such
as population bottlenecks and drift. Variation in genetic variation across diverse taxa is
predicted by population size so drift may be an important force maintaining variation.
Most mutations appear neutral or slightly deleterious
Yet mutations can also be adaptive.
There is still some debate about the forces maintaining genetic diversity. Why is it not all
lost/purged from the population? “classical school”, vs “balancing selection” school vs.
neutral/nearly neutral school.
93
Some key terms you’ve heard today
(they’ll appear more throughout the course)
Variation change, descent with modification, natural selection
Mendelian genetics: segregation, independent assortment, dominance/additivity
Discrete vs continuous traits
The ”modern synthesis” of evolution
Different types of selection: Natural selection, purifying selection, balancing selection
Drift
Phenotypic variation. P ~ G + E + GxE
Heritability
Gene x environment effects, reaction norms
Phenotypic plasticity: plasticity constrains or facilitates rapid adaptation?
Heritable genetic variation
Allele, Genotype, Haplotype, chromosome homologs
Heterozygous, Homozygous
Recessive, additive, dominant alleles
Gene, locus, non-coding, intergenic, regulatory
Mutations types: e.g single nucleotide polymorphisms (SNPs), microsatellite repeat number
Mutation effect size and direction: strong/weak, beneficial/neutral/deleterious
Percentage of polymorphic sites, percentage of heterozygous sites, nucleotide diversity
Pleiotropy
Tomorrows topic: Hardy-Weinberg equilibrium
The use of population genetics to study evolution
Determine allele and genotype frequencies to detect the presence
and the mechanisms of evolutionary change
Hardy-Weinberg equilibrium (HWE): frequencies of alleles and genotypes remain
unchanged from generation to generation
Frequencies do not change on their own
Deviations from HWE can provide indication for evolutionary processes
Herron & Freeman (Chapter 6): Mendelian genetics in
populations (pages 193 - 205)
Crucial concepts & definitions you need to know for tomorrow!
Phenotype
Genotype, Homozygous, Heterozygous
Gene locus
Alleles
Chromosome homologues
Homozygous / heterozygous
Dominant / recessive
96
Further information for those interested…
Mendel’s three laws of inheritance
Gregor Mendel,
1822-1884
i. Law of segregation
(diploid alleles separate in gametes)
Gregor Mendel,
1822-1884
A
Aa
Mendel’s laws of inheritance:
1. Law of segregation (diploid alleles separate in gametes)
a
1n
2n
organism gametes
II. Law of independent assortment
(alleles of unlinked genes separate independently)
Gregor Mendel,
1822-1884
B
b
Mendel’s laws of inheritance:
1. Law of segregation (diploid alleles separate in gametes)
Bb
B
2. Law of independent assortment (alleles of different genes separate
independently of one another)
b
2n
organism
1n
gametes
III. Law of dominance
when two alleles, a dominant allele can mask recessive allele
Gregor Mendel,
1822-1884
Mendel’s laws of inheritance:
1. Law of segregation (diploid alleles separate in gametes)
2. Law of independent assortment (alleles of different genes separate
independently of one another)
3. Law of dominance (when two alleles at a locus are present, the dominant
allele can mask the effects of the weaker allele)
Tall allele is dominant over
recessive dwarf alllele
What role might plasticity play in evolution?
Two competing schools of thought:
1. Plasticity “buffers” or “constrains” adaptive evolution
(it dampens response to selection by obscuring the beneficial heritable genotype)
‘Plasticity “hides” the true phenotypic “read-out” of a genotype’
Example reasoning:
1. Blue individuals are fittest. Selection favors ”blueness”.
Phenotype / Trait
(Blue-ness)
Genes x Env
2. GxE interaction:
G2 (BB homozygote) is blue in all conditions
G1 (bb)
G1 (bb homozygote) is plastic: red in E1 and blue in E2
G2 (BB)
Blue genotype (G2) is fittest.
3. Selection acts at the phenotypic level, and can only distinguish between G2 and G1
in some circumstances (E1). In E2 they look phenotypically the same.
E1
E2
4. The rate at which the populations is fixed for the beneficial B allele is slowed down,
because bb alleles persist in some circumstances. Selection is inefficient.
What role might plasticity play in evolution?
Two competing schools of thought:
1. Plasticity “buffers” or “constrains” adaptive evolution
(it dampens response to selection by obscuring the beneficial heritable genotype)
‘Plasticity “hides” the true phenotypic “read-out” of a genotype’
2.
Plasticity facilitates adaptive evolution
(when the environment changes, one part ot the plastic response may be favored).
Example reasoning:
Phenotype / Trait
(Blue-ness)
Genes x Env
E1
1. The selection pressure changes and favors the red phenotype.
G1 (bb)
2.
Plasticity of G1 (bb) individuals means they are fitter in E1 than G2 (BB).
G2 (BB)
3.
The population can persist in E1.
E2
4. New or existing genetic variation is “exposed” to new selection presure, they
stabilize / reinforce the trait.
5. Selection can now favor red phenotypes that are produced even without
environmental trigger (plasticity). Ie. It becomes fixed or “assimilated”
Sexual reproduction is an important source of multilocus genetic variation:
Recombination - existing variation ”reshuffled” by meiosis
ATAGATGCATCAGGGTGG homolog 1
crossing over X
ATAGATGCACCAGGGTGG homolog 2
ATAGATGCATCAGGGTGG
ATAGATGCATCAGGGTGG
ATAGATGCATCAGGGTGG
parent1
ATAGATGCACCAGGGTGG gametes
fertilization
ATAGATGCACCAGGGTGG diploid offspring
ATAGATGCATCAGGGTGG with novel haplotypes
Three sources of genetic variation from sexual reproduction:
1. Independent assortment of chromosomes during meiosis
e.g. humans: max 223 possible chromosome combinations from one parent.
2. During meiosis, homologous chromosomes align, and at least 1 cross-over occurs.
Alleles previously on opposite chromosome homologs can become linked
Alleles linked on the same chromosome homolog can be unlinked
e.g. humans: >> 423 possible chromosome combinations from one parent.
3. During fertilization, the union of gametes brings together different combinations of alleles from meiosis in
both parents.