Download Lecture PDF - Carol Eunmi LEE

Carol Eunmi Lee
10/18/16
Natural Selection
Natural
An Adaptive Mechanism
Selection
Evolutionary Mechanisms
Darwin
Evolution acts through
changes in allele frequency
at each generation
Genetic Drift
Non-adaptive
Migration
According to Darwin, this
happens via
Mutations
Natural Selection
Adaptive
Natural Selection
(HeconsideredSelectiononly,andnot
otherevolutionarymechanisms,suchas
mutations,geneticdrift,etc.)
Sources of Genetic Variation
Mutation generates
genetic variation
Natural Selection
Natural Selection acts on
genetic or epigenetic
variation in a population
Epigenetic modification
changes expression of
genes
Genetic Drift can reduce
genetic variation
Without genetic or
epigenetic variation,
Natural Selection cannot
occur
Title goes here
OUTLINE
(1) General Description of Natural Selection
(2) Distinguishing between Phenotypic
Plasticity (Acclimation) vs. Natural Selection
(Adaptation)
(3) Modes of Natural Selection
(4) Natural Selection Violating Hardy-Weinberg
Equilibrium
1
Carol Eunmi Lee
10/18/16
Darwin’s contribution:
Natural Selection
Population Speciation as a result of Natural Selection
■
Toomanyoffspringproduced
■
Limitedresourcesandcompetition
Differentialfitness (survivalandreproduction) of
differentheritable (genetically-basedinherited)
phenotypes(NOTplasticphenotypes) becausesome
arebettersuitedtotheenvironmentthanothers
■
Variationinapopulation
NaturalSelectionleadstoà ADAPTATION
■
Betteradaptedindividualssurvive
■
Survivorsleavemoreoffspring
■
Thus,averagecharacterofpopulationisaltered
NOTrandom,butdeterministic
8
Natural Selection
Darwin
■
SO… The important point is
that Natural Selection is all
about who lives and who
dies (and reproduces)
“Population speciation”
The important factor is: FITNESS
9
Darwin
Darwin
mutation
Title goes here
Selection
favors
2
Carol Eunmi Lee
10/18/16
Selection on pathogens imposed
AZT
by Drugs (refer to Lecture 1)
Darwin
■
Greater
Fitness
■
■
AZT(Azidothymidine)isathymidine
mimicwhichstopsreversetranscription
Mutationsinthereversetranscriptase
geneofHIVarisessuchthattheenzyme
canrecognizeAZT
ThedrugsimposeSelectiononthevirus.
Geneticvariation(generatedby
mutations)allowsthevirustorespond
toselectionandevolvedrugresistance
Evolution of HIV resistance in Human Populations
■
■
■
■
■
Frequency shift in CCR5- D32 allele
CCR5-Δ32 (or CCR5-D32 or CCR5 delta 32) is a mutant
allele of the receptor CCR5, where the deletion of a 32 base
pair segment makes the receptor nonfunctional
Fr
The allele has a negative effect upon T cell function, but
appears to protect against smallpox and HIV
HIV has no receptor to bind to and cannot enter the cell
This allele is found in 14% of Europeans
HIV can impose selective pressure for CCR5-Δ32, increasing
the frequency of this allele in human populations (Sullivan et
al. 2001)
Amy D. Sullivan et al. 2001. The coreceptor
mutation CCR5Δ32 influences the dynamics
of HIV epidemics and is selected for by HIV.
Proc Natl Acad Sci USA. 98: 10214–10219.
Selection imposed by Transmission Rate
on Virulence of HIV
■
■
■
Need to keep host alive long enough to get passed
on to the next host
(Evolutionary tradeoff between fast population growth
and keeping the host alive)
Selection on Virulence
■
High Transmission Rate: will select for High Virulence
High Transmission rate : High Virulence
(Can grow fast and jump to the next host; ok if host dies;
genetic strain that grows faster will win)
Low Transmission Rate : Low Virulence
(More virulent strains would die with the host and get
selected out; less virulent strain will win)
18
Title goes here
3
Carol Eunmi Lee
10/18/16
High Transmission Rate
Selection on Virulence
■
Low Transmission Rate: will select for Low Virulence
Ifthevirusislikelytomovetoanewhost,thefaster
growing(andmorevirulent)strainislikelytoovertake
theslowerstrainsand“win”
■
It’soktokillthehost,sincethechancesofjumpingto
anewhostishigh
■
■
NaturalselectionwillfavortheMOREvirulentstrain
19
Low Transmission Rate
Ifthevirusisnotlikelytomovetoanewhostthe
slowergrowing(andlessvirulent)strainislikelyto
“win”
20
Evolution of Virulence
■
■
It’snotoktokillthehost,sincethechancesofjumping
toanewhostislow.Iftheviruskillsthehost,itwillkill
itself
■
■
NaturalselectionwillfavortheLESSvirulentstrain
The direction of selection
could change as the
environment changes
21
22
Conceptual Confusions
Selection vs. Plasticity
Title goes here
Trait variation is often assumed to be
due to Adaptation, when the differences
might be due to Phenotypic Plasticity or
nonadaptive genetic causes
4
Carol Eunmi Lee
10/18/16
Not All Phenotypic Variation is due to
Adaptation
Phenotypicchangeandvariationcouldhaveother
causes:
– PhenotypicPlasticity:Changesthatarenotdueto
geneticchanges,butduetochangesingene
expression
Nature vs. Nurture
• Bothenvironmentandgeneticsaffectmany
traits,butneedtoexperimentallyorstatistically
separatethesefactors
• How?
– ChangesthatareGenetic,butNOTadaptive:
• GeneticDrift: randomchance
•LinkageandGeneticHitchhiking:
Geneticchangesthatoccur
becausethegenewasrightnexttoanothergeneonachromosomethat
wasunderselection
• Constraint:physicalorstructural(liketheSpandrels)
Adaptation
Requires Natural Selection
Requires polymorphism in a population
• Example:Common-gardenexperiment
• Havingappropriatecontrols
• Statisticallyassessingtheeffectofenvironment
How can you tell if a trait evolved as a
result of Adaptation (and due to
Natural Selection)?
(1)Thetraitmustbeheritable
(2)Thedifferencesbetweenpopulationsare
geneticallybaseddifferencesratherthaninducible
differences(plasticity)
MUST have an effect on Fitness
Is a frequency (%) change in a population
(3)Thetraithasfitness consequences(promotes
survival,performance,andnumberofoffspring)
There must be a Selective Force
(Ifatraitevolvedduetogeneticdrift,linkageor
pleiotropy,thechangeisgenetic,butmayconfer
nofitnessadvantage)
PhenotypicPlasticity
Definition
Acclimation (≠ Adaptation)
• Differencesinphenotypethatagenotypeexhibits
acrossarangeofenvironments,becauseofchanges
ingeneexpression
• Changesingeneexpressioncouldbecauseby
environmentalcuesinstigatingsignaltransduction...
changesingeneexpressioncouldalsobecausedby
epigeneticmodifications
• Sometraitswithaplasticcomponent:intelligence,
height,temperaturetolerance,salinitytolerance,
musclemass…
Title goes here
1) Result of Phenotypic Plasticity
2) Not heritable (Not inherited)
3) Short term or developmental response
within a single generation
4) Arises through differential gene expression
or other regulatory mechanism rather than
natural selection
5
Carol Eunmi Lee
10/18/16
Allele A1 Demo
Allele A1 Demo
Genetic Drift can interfere with Natural
Selection
■
■
■
With Selection, what matters is the
RELATIVE fitness of different
genotypes
Recessive deleterious alleles are harder to
remove by negative selection because their
phenotype is hidden in the heterozygous state
■
For instance, putting 1.0 and 0.9 is
the same as putting 1000 and 900
for fitness values of genotypes
However, dominant beneficial alleles are more
difficult drive to fixation by positive selection,
because they are dragging recessive alleles
along in the heterozygous state
■
31
32
Allele A1 Demo
■
■
However, dominant beneficial alleles are more
difficult drive to fixation by positive selection,
because they are dragging recessive alleles
along in the heterozygous state
• Positive Selection: Selection
favoring an allele or a heritable
trait
Although, if recessive beneficial alleles are
very rare they will take longer to fix because
most will be in the heterozygous (rather than
homozygous state)
• Negative Selection: Selection
disfavoring an allele or a heritable
trait
33
SelectiononDominantvsRecessiveAlleles
■
■
■
Herron & Freeman
Selection against recessive allele
Set fitness of genotypes to:
WAA = 1, WAa = 1, Waa = 1 – s
(s = selection coefficient)
Selection against dominant allele
Set fitness of genotypes to:
WAA = 1 - s, WAa = 1 - s, Waa = 1
(AA and Aa have same phenotype)
Title goes here
34
SelectiononDominantvsRecessiveAlleles
■
■
■
What Happens?
Selection against recessive allele
In Allele A1, set fitness of genotypes to:
WAA = 1, WAa = 1, Waa = 1 – s
(s = selection coefficient)
Selection against dominant allele
Set fitness of genotypes to:
WAA = 1 - s, WAa = 1 - s, Waa = 1
(AA and Aa have same phenotype)
6
Carol Eunmi Lee
10/18/16
SelectiononDominantvsRecessiveAlleles
■
Selection against recessive allele:
◆
◆
Selection on Discrete vs
Continuous characters
■
As recessive allele becomes rare, rate of its
disappearance slows down
As homozygote recessive allele becomes
rare, most are in the heterozygous state and
are masked from selection
◆
◆
■
■
Selection against dominant allele:
◆
Whenphenotypesfallintodiscreteclasses,wecan
thinkofselectionactingdirectlyongenotypes
Dominant allele that is disfavored by selection
is removed quickly from the population
Suchdiscretetraitsareusuallycodedbyoneorafew
genes(loci)
Mendel’syellowvs.greenpeas
However,whenphenotypesfallintoacontinuum,
becausetheyareencodedbymanyloci,youwillsee
changesinthedistributionsoftraits(nextslide)
◆
◆
ContinuoustraitssuchasthoseDarwinexamined,beak
shape,bodysize,haircolor,etc.
suchtraitsarecalled“quantitativetraits”
38
Distribution of discrete versus continuous traits
Frequency
ina
population
Trait1
Trait2
DiscreteTraits:Traitsthatoccur
indiscretecategories;
Examples: Mendel’straits(green
andyellowpeas,wrinkledand
smoothpeas) (theseareencoded
bysingleloci)
Alsodiscretetraitsencodedby
multipleloci:fingernumber,
clutchsize
Modes of Selection
ContinuousTraits:Traitsthat
varyalongacontinuum;
(mosttraits)
Examples:bodysize,height,
IQ,bloodpressure,milk
yield,fatcontent,feather
color,beakshape,limb
length,haircolor,etc...
39
DIFFERENT MODES OF SELECTION
Directional Selection:
Directional Selection
Stabilizing Selection
Disruptive Selection
Selection favors an extreme
phenotype and causes a shift in allele
frequencies toward that direction
Balancing Selection
■
Genetic diversity is reduced at the
relevant loci
(knock out maladapted genotypes)
■
Examples:
■
■
■
41
Title goes here
Drug-resistance in tuberculosis and
HIV
Agriculture: artificial selection for
specific traits
Sexual selection for a trait (e.g. for
42
bright plumage, peacock tail)
7
Carol Eunmi Lee
■
10/18/16
Does sexual selection typically
act on more on males or females?
43
Sexual Directional Selection:
Pheasants
Selection favors an extreme
phenotype and causes a shift in allele
frequencies toward that direction
Unable to
Reproduce
44
■
Most of the males do not mate, so
their genotypes (and phenotypes) are
removed from the population à
genetic diversity reduced at the
relevant loci
■
The population shifts toward the
extreme trait (e.g. plumage, body size,
etc)
zero
30+
Largevarianceinmale
reproductivesuccess,
withmanyproducing
fewtonooffspring,and
afewmalesproducing
lotsofoffspring
45
Directional Selection on
pathogens imposed by Drugs
• In the presence of AZT, Natural
Selection favors mutants that
are resistant to AZT (blue, have
(refer to Lecture 1)
■
■
■
46
slow & careful enzyme)
AZT
AZT(Azidothymidine)isathymidine
mimicwhichstopsreversetranscription
Results in %change in
the population, toward
higher % of AZT
resistant mutants
Mutationsinthereversetranscriptase
geneofHIVarisessuchthattheenzyme
canrecognizeAZT
ThedrugsimposeSelectiononthevirus.
Geneticvariation(generatedby
mutations)allowsthevirustorespond
toselectionandevolvedrugresistance
Title goes here
47
48
8
Carol Eunmi Lee
10/18/16
Directional Selection
Directional Selection on a continuous trait
49
Directional Selection during Domestication
■
■
■
Corn
Morphological differences between teosinte and
maize
Rapid evolution under
intense directional
selection for large and
numerous kernals
■
• Has
branching
patterns like
teosinte
Selection by humans for
a few regulatory genes
(affecting transcription)
Reduced genetic
diversity in domesticated
corn
Genes selected for in Corn
teosinte
maize
Hardy Weinberg revisited
F1 Hybrid
Teosinte
Major morphological
differences are due to
directional selection on 5
genes
Genes:
• Teosinte branched1 (tb1): single
mutation affects branching and
inflorescence
• Regulator of tb1
• tga glume (outer coating)
reduction on chromosome X
• teosinte – ~8-12 kernels
F1 hybrid 8 rows, corn 20+rows
Evidence for selection in 2-4%
of genes, ~1200 genes
Title goes here
Maize with tb1
knocked out
Generation 1
Generation 2
Generation 3
AA
Aa
aa
250
750
900
500
200
90
250
50
10
(1) Is this population remaining in HW Equilibrium
from generation to generation?
(2) What might be going on?
9
Carol Eunmi Lee
10/18/16
AA
Hardy Weinberg revisited
Generation 1
Generation 2
Generation 3
AA
Aa
aa
250
750
900
500
200
90
250
50
10
aa
0.40
0.60
0
Gen2
Freq of A (p) = 0.75 + (0.20/2) = 0.85
**Genotype frequencies deviated from expectations based on allele
frequencies: freq of A is 0.5 in Gen1, so expect AA =0.25 at Gen2,
55
(2) What might be going on? Directional selection favoring AA?
Hardy Weinberg revisited
AA
Aa
aa
0.40
0.60
0
(1) Is this population in HW Equilibrium? NO
(2) Are the HW expectations the same as the
genotype frequencies above? NO
(2) Are the HW expectations the same as the
genotype frequencies above?
Freq of A (p) = 0.40 + (0.60/2) = 0.70
Freq of a (q) should be = 1 - 0.70 = 0.30
Hint: Calculate the genotype frequencies from the #
above, and then calculate allele frequencies. Use the
allele frequencies to calculate HW expectations.
57
Stabilizing Selection
■
Selection favoring intermediate trait
values
■
The average trait value stays the
same
■
Genetic diversity is reduced at the
relevant loci
■
Examples:
Favors
Freq of A (p) = 0.25 + (0.50/2) = 0.50
Freq of a (q) should be = 1 -0.50 = 0.50
**Allele and genotype frequencies are changing across generations: freq of A
is increasing across the 3 generations
(1) Is this population in HW Equilibrium?
(3) What might be going on?
Gen1
Freq of a (q) = 1-0.85 = 0.05 + (0.20/2) = 0.15
Hardy Weinberg revisited
Aa
250
50
10
Gen3 - can do same calculations
***check if (a) alleles frequency changes across generations
and (b) where allele frequency yields predicted genotype
frequencies
AA
aa
(1) Is this population remaining in HW Equilibrium from generation to
generation? NO
(1) Is this population remaining in HW Equilibrium
from generation to generation?
(2) What might be going on?
Aa
Generation 1
250 (freq = 250/1000)
500
Generation 2
750 (freq = 750/1000)
200
Generation 3
900 (freq = 900/1000)
90
First convert # of individuals to frequency of genotypes
Based on HW expectations, freq of aa should = 0.3 x 0.3 = 0.09
aa is missing!
aa might be a homozygous recessive lethal
58
à Negative selection acting against aa?
Example of Stabilizing Selection
Selection for an
optimal number of
eggs
Selection for an optimal number of
fingers
Selection for optimal body size
59
Selection for optimal number of offspring
Title goes here
10
Carol Eunmi Lee
10/18/16
Disruptive Selection
Disruptive Selection
■
Selection favors the extremes
■
Genetic diversity is increased (favor
novel beneficial alleles; knock out alleles
that code for intermediate traits)
■
Can lead to formation of new species
■
Examples:
■
■
■
■
Balancing Selection
■ Balancing
Niche Partitioning (Specialization on
different resources, food)
Differences in habitat use
Will discuss more in lecture on
Speciation
Sexual selection for different traits
(blue birds mate with blue, red birds
mate with red)—intermediate colors
selected against
(on discrete or continuous traits)
Balancing Selection
■
Selection is a generic term to refer to
any type of selection that acts to maintain genetic
variation in a population
■
There are different mechanisms: Fluctuating selection,
selection favoring heterozygote (overdominance),
frequency-dependent selection, etc.
■
Examples:
■
■
■
Selection for heterozygotes (sickle cell anemia, and
cystic fibrosis)
Selection for different traits in different environments
Selection for different traits at different times (fluctuating
selection)
Overdominance: Selection favoring the
heterozygote
Generation 1
Generation 2
Generation 3
Generation 1
Generation 2
Generation 3
■
■
■
Genetic diversity is maintained in a population in
this case because the heterozygote maintains both
alleles
■
Example: Sickle Cell anemia
An Example of one mechanism:
Generation 1
Generation 2
Generation 3
In this case, allele frequencies (of A and a) do not
change. However, the population did go out of HW
equilibrium because you can no longer predict
genotypic frequencies from allele frequencies
Title goes here
■
Overdominance: Selection favoring the heterozygote
aa
0.25
0.20
0.10
For example, for p = 0.5, the HW expected p2 = 0.25,
but in Generation 3, the observed p2 = 0.10
aa
0.25
0.20
0.10
64
Overdominance: Selection favoring the heterozygote
Aa
0.50
0.60
0.80
Aa
0.50
0.60
0.80
Balancing Selection
An Example of one mechanism:
AA
0.25
0.20
0.10
AA
0.25
0.20
0.10
63
Balancing Selection
■
An Example of one mechanism:
■
65
AA
0.25
0.20
0.10
Aa
0.50
0.60
0.80
aa
0.25
0.20
0.10
Why is this NOT stabilizing selection?
In Stabilizing Selection, genetic diversity decreases
as the population stabilizes on a particular trait
value (a multilocus quantitative trait, like body size,
height, clutch number, finger number, intermediate
66
color –typically of a multilocus nature)
11
Carol Eunmi Lee
10/18/16
Sickle cell anemia
Sickle cell anemia
example of balancing selection
■
■
■
Reducedabilityofredbloodcellstocarryoxygen
(mutationinHbSgene,makesdefectivehemoglobin
protein)
HAHA:homozygous,noeffectsofdisease(sicklecell
anemia)
■
HAHs:heterozygotes,suffermildeffects
■
HsHs:homozygous,usuallydiebeforereproduction
■
■
In the absence of malaria, which genotype would be
favored? Which mode of selection would be acting?
68
Sickle cell anemia
When Malaria is present HAHs advantage: red blood cells
with abnormal hemoglobin tend to sickle when infected by
parasite and are culled out
■
When Malaria is not present, AA advantage:
US African Americans: 91.26% H A H A ; 8.54% H A H s ; 0.2% H s H s
■
■
With malaria, balancing selection favors the heterozygote
■
Without malaria, directional selection favors HAHA
69
When Malaria is present HAHs advantage: red blood cells
with abnormal hemoglobin tend to sickle when infected by
parasite and are culled out
With malaria, balancing selection favors the heterozygote
because of increased malaria resistance, even though
oxygen carrying capacity is lowered
Example from Africa: 73.7% HAHA; 24.3% HAHs; 2% HsHs
■
In the presence of malaria, which genotype would be
favored? Which mode of selection would be acting?
67
Sickle cell anemia
■
BUT... When Malaria is present HAHs advantage: red
blood cells with abnormal hemoglobin tend to sickle when
infected by parasite and are culled out
■
The homozygous wild type HAHA is disfavored because
resistance to malaria is low
The homozygous mutant HsHs is disfavored because it is
70
lethal
Hardy Weinberg problem
using actual data
■
■
■
71
Title goes here
1 in 5000 individuals have sickle cell
disease and are homozygous for the sickle
cell hemoglobin (HsHs)
What are the expected genotype
frequencies of the HAHA, HAHs, and HsHs
genotypes in the population?
What are the frequencies of HA and Hs
alleles?
72
12
Carol Eunmi Lee
10/18/16
■
Detecting Selection
■
■
RNA Codons
(1)
So, how does one detect Natural
Selection in a population?
Many types of tests
The challenge is distinguishing
natural selection from signatures of
Genetic Drift
Simplest Test: Ka/Ks Test
Nonsynonymous substitution rate
Synonymous substitution rate
In the case of amino
acids
§
Mutations in Position 1,
2 lead to Amino Acid
change
§
■
Ks is used here as the “control”, proxy for neutral evolution
■
Synonymous substitution rate
■
■
■
A greater rate of nonsynonymous substitutions (Ka) than
synonymous (Ks) is used as an indication of selection
(Ka/Ks >1)
Substitution rate: out of all the possible number of
mutations, how many fixed
Summary
Ka/Ks Test
Nonsynonymous substitution rate =
1
Need coding sequence (sequence that codes proteins)
■
(1)
Ka
Ks >
■
Mutations in Position 3
often don’t matter
§
=
Ka
>
Ks
1
(1)OftheevolutionaryforcesthatcandisruptHWEquilibrium,
NaturalSelectionistheonlyonethatisadaptive
In the absence of selection, you’d expect Ks = Ka, and for
Ka/Ks = 1
(2)Selectionoccursthroughdifferentialreproductionwhichis
NOTrandom
A greater rate of nonsynonymous substitutions (Ka) than
synonymous (Ks) is used as an indication of positive
selection (Ka/Ks >1)
(3)Naturalselectionrequiresgeneticvariationuponwhichitcan
act
If Ks > Ka, or Ka/Ks < 1, that would suggest purifying
selection, that selection might be preserving amino acid
composition
Title goes here
(4)Therearedifferentwaysinwhichselectioncanact(favoring
theextremes,orheterozygotes,orunidirectional)
13
Carol Eunmi Lee
10/18/16
The following are numbers of red, pink, and white flowers in a
population.
Concepts
Natural Selection
Fitness
Directional,
Stabilizing,
Disruptive Selection
Balancing Selection
Selection on dominant
vs recessive alleles
(A1A1)
Red
(A1A2)
Pink
(A2A2)
White
Generation 1:
400
200
400
Generation 2:
600
100
300
Generation 3:
500
0
500
1. Is the population above in Hardy-Weinberg Equilibrium?
(A) Yes
(B) No
(C) Yes in the first generation, but No in the third generation
(D) No in the first generation, but Yes in the third generation
2. What are the frequencies of alleles and
genotypes at Generation 3?
(A)A1: 0.50, A2: 0.50
A1A1: 0.25, A1A2: 0.50, A2A2: 0.25
(B)A1: 0.65, A2: 0.35
A1A1: 0.60, A1A2: 0.10, A2A2: 0.30
(C)
A1: 0.50, A2: 0.50
A1A1: 0.50, A1A2: 0, A2A2: 0.50
(D)
3. In the previous example (from question #1), what
might be going on?
(A) Genetic Drift
(B) Balancing Selection
(C) Recombination
(D) Directional Selection
(E) Disruptive Selection (but, rare for single locus
trait)
A1: 0.50, A2: 0.50
A1A1: 0.25, A1A2: 0, A2A2: 0.25
Answers:
4. What would Darwin say?
(A) Genetic drift is also an important evolutionary force
that occurs through random survival and reproduction
(B) Individuals pass alleles onto their offspring intact
(inheritance is particulate)
1B
2C
3E
4D
(C) Selection acts on genetic variation such as Mutations
(D) Selection acts on differential fitness of individuals
that vary in heritable traits in a population
(E) Evolution occurs at the level of the individual
Title goes here
14