Natural Selection

Natural

Selection

Natural Selection

An Adaptive Mechanism

Evolutionary Mechanisms

Genetic Drift MigrationMutationsNatural Selection

Non-adaptive

Adaptive

Evolution acts through changes in allele frequency at each generation

According to Darwin, this happens via Natural Selection

(He considered Selection only, and not other evolutionary mechanisms, such as mutations, genetic drift, etc.)

Darwin

Natural Selection

Without genetic or epigenetic variation, Natural

Selection cannot occur

Mutation generates genetic variation

Epigenetic modification changes expression of

genes

Genetic Drift can reduce genetic variation

Sources of Genetic Variation

Natural Selection acts on genetic or epigenetic

variation in a population

OUTLINE

(1) General Description of Natural Selection(2) Modes of Natural Selection(3) Selection Violating Hardy-Weinberg

Equilibrium

Darwin’s contribution:

Population Speciation as a result of Natural Selection

Too many offspring produced Limited resources and competition Variation in a population Better adapted individuals survive Survivors leave more offspring Thus, average character of population is altered

Natural SelectionThe differential survival and/or reproduction of classes of entities that differ in one or more characteristics

The only evolutionary force that is ADAPTIVE

NOT random, but deterministic

Darwin

Population speciation

Darwin Population speciation

mutation


Selection favors


GreaterFitness

Selection on pathogens imposed by Drugs (refer to Lecture 1)

AZT (Azidothymidine) is a thymidine mimic which stops reverse transcription

Mutations in the reverse transcriptase gene of HIV arises such that the enzyme can recognize AZT

The drugs impose Selection on the virus. Genetic variation (generated by mutations) allows the virus to respond to selection and evolve drug resistance

AZT

Selection imposed by Transmission Rate on Virulence of HIV

Need to keep host alive long enough to get passed on to the next host (Tradeoff between fast population growth and keeping the host alive)

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)

High Transmission Rate

If the virus is likely to move to a new host the faster growing (and more virulent) strain is likely to overtake the slower strains and “win”

It’s ok to kill the host, since the chances of jumping to a new host is high

Natural selection will favor the more virulent strain

Low Transmission Rate

If the virus is not likely to move to a new host the slower growing (and less virulent) strain is likely to “win”

It’s not ok to kill the host, since the chances of jumping to a new host is low. If the virus kills the host, it will kill itself

Natural selection will favor the less virulent strain

Evolution of HIV resistance in Human Populations

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.

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

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)

FrFrequency shift in CCR5- D32 allele

Modes of Selection

Selection on discrete vs continuous characters When phenotypes fall into discrete classes (like

Mendel’s yellow vs green peas), we can think of selection acting directly on genotypes Such discrete traits are usually coded by one or a

few genes (loci)

However, when phenotypes fall into a continuum (continuous traits such as those Darwin examined, beak shape, body size), you will see changes in the distributions of traits (next slide) –such traits are called “quantitative traits,” coded by many loci

DIFFERENT MODES OF SELECTION(Herron & Freeman Section 9.6)

Directional Selection on a continuous trait

Directional Selection on a discrete trait

Directional Selection: Selection changes frequency of alleles in one direction

die

shift in distribution

Directional Selection: Selection changes frequency of alleles in one direction

AA Aa aaGeneration 1 0.80 0.15 0.05Generation 2 0.60 0.30 0.10 . . . . . . . . . . . .Generation X 0.04 0.16 0.75

Mock Example



How will selection act if A is dominant and selection favors red?

AA Aa aa

How will selection act if A is not dominant, but Aa intermediate?

AA Aa aa

Under which situation will the “a” allele be preserved in the population longer?


How will selection act if A is dominant and selection favors red?

AA Aa aa

Selection will act on AA and Aa in the same manner

How will selection act if A is not dominant, but Aa intermediate?

AA Aa aa

Selection will act more strongly on AA

Under which situation will the “a” allele be preserved in the population longer?

The first above, as the “a” allele is more effectively masked in the heterozygote state


Selection on Dominant vs Recessive Alleles Herron & Freeman

Selection against recessive alleleSet fitness of genotypes to:

WAA = 1, WAa = 1, Waa = 1 – s (s = selection coefficient)

Selection against dominant alleleSet fitness of genotypes to:

WAA = 1 - s, WAa = 1 - s, Waa = 1(AA and Aa have same phenotype)

Selection on Dominant vs Recessive Alleles What Happens?

Selection against recessive alleleIn Allele A1, set fitness of genotypes to:

WAA = 1, WAa = 1, Waa = 1 – s (s = selection coefficient)

Selection against dominant alleleSet fitness of genotypes to:

WAA = 1 - s, WAa = 1 - s, Waa = 1(AA and Aa have same phenotype)

Selection on Dominant vs Recessive Alleles

Selection against recessive allele: 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: Dominant allele that is disfavored by selection

is removed quickly from the population

Directional Selection:

Selection changes frequency of alleles in one direction

Genetic diversity is reduced (knock out maladapted genotypes)

Examples: Drug-resistance in tuberculosis and

HIV Agriculture: artificial selection for

specific traits Sexual selection for a trait (e.g. for

bright plumage)

Directional Selection

Rapid evolution under intense directional selection for large and numerous kernals

Selection by humans for a few regulatory genes (affecting transcription)

Reduced genetic diversity in domesticated corn

Directional Selection during Domestication

Morphological differences between teosinte and maize

Maize with tb1 knocked out

maizeteosinte

• Has branching

patterns like teosinte

Major morphological differences are due to directional selection on 5 genesGenes: • 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

Teosinte

Corn

F1 Hybrid

Genes selected for in Corn

Hardy Weinberg revisited

AA Aa aaGeneration 1 250 500 250Generation 2 750 200 50Generation 3 900 90 10

(1) Is this population remaining in HW Equilibrium from generation to generation?

(2) What might be going on?


AA Aa aaGeneration 1 250 500 250Generation 2 750 200 50Generation 3 900 90 10

(1) Is this population remaining in HW Equilibrium from generation to generation?

***check if (a) alleles frequencies change across generations and (b) whether the allele frequencies do not yield the predicted genotype frequencies


AA Aa aaGeneration 1 250 (freq = 250/1000) 500 250Generation 2 750 (freq = 750/1000) 200 50Generation 3 900 (freq = 900/1000) 90 10First convert # of individuals to frequency of genotypes

(1) Is this population remaining in HW Equilibrium from generation to generation? NOGen1 Freq of A (p) = 0.25 + (0.50/2) = 0.50

Freq of a (q) should be = 1 -0.50 = 0.50Gen2 Freq of A (p) = 0.75 + (0.20/2) = 0.85

Freq of a (q) = 1-0.85 = 0.05 + (0.20/2) = 0.15Gen3 - can do same calculations

**Allele and genotype frequencies are changing across generations: freq of A is increasing across the 3 generations

**Genotype frequencies deviated from expectations based on allele frequencies: freq of A is 0.5 in Gen1, so expect AA =0.25 at Gen2,

(2) What might be going on? Directional selection favoring A?


AA Aa aa0.44 0.56 0

(1) Is this population in HW Equilibrium?

(2) Are the HW expectations the same as the genotype frequencies above?

Hint: Calculate the genotype frequencies from the # above, and then calculate allele frequencies. Use the

allele frequencies to calculate HW expectations.


Hardy Weinberg revisitedAA Aa aa0.40 0.60 0

(1) Is this population in HW Equilibrium? NO

(2) Are the HW expectations the same as the genotype frequencies above? NO

Freq of A (p) = 0.40 + (0.60/2) = 0.70Freq of a (q) should be = 1 - 0.70 = 0.30

Based on HW expectations, freq of aa should = 0.3 x 0.3 = 0.09

aa is missing! Negative selection acting against aa?aa might be a homozygous recessive lethal

Stabilizing Selection (on discrete or continuous traits)

Selection acts against the extremes (favors intermediate trait) =purifying selection

The average trait value stays the same

Genetic diversity is reduced

This is going on all the time, as deleterious alleles are getting selected out of the population

Examples: Selection against new harmful mutationsSelection for an optimal number of fingersSelection for optimal body size

die

Example of Stabilizing Selection

Selection for an optimal number of

eggs

Disruptive Selection (on discrete or continuous traits) Selection favors the extremes

Genetic diversity is increased (help maintain genetic variation; knock out alleles that code for intermediate traits)

Can lead to formation of new species Examples:

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

Disruptive Selection

Balancing Selection (on discrete or continuous traits)

Balancing 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)

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)

Balancing Selection An Example of one mechanism:

Overdominance: Selection favoring the heterozygote

AA Aa aaGeneration 1 0.25 0.50 0.25Generation 2 0.20 0.60 0.20Generation 3 0.10 0.80 0.10

Genetic diversity is maintained in a population in this case because the heterozygote maintains both alleles

Example: Sickle Cell anemia

Balancing Selection An Example of one mechanism:

Overdominance: Selection favoring the heterozygoteAA Aa aa

Generation 1 0.25 0.50 0.25Generation 2 0.20 0.60 0.20Generation 3 0.10 0.80 0.10

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

For example, p = 0.5, p2 = 0.25, but in Generation 3, the observe p2 = 0.10

Balancing Selection

An Example of one mechanism:



Genetic diversity is maintained in a population in this case because the heterozygote maintains both alleles

Example: Sickle Cell anemia

Balancing Selection

An Example of one mechanism:



Why is this NOT stabilizing selection? In Stabilizing Selection genetic diversity decreases as the population stabilizes on a particular trait value (a quantitative trait, like body size, height, intermediate color –of a multilocus nature)

Sickle cell anemiaexample of balancing selection

Reduced ability of red blood cells to carry oxygen (mutation in HbS gene, makes defective hemoglobin protein)

HAHA: homozygous, no effects of disease (sickle cell anemia)

HAHs: heterozygotes, suffer mild effects

HsHs: homozygous, usually die before reproduction

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

72% HAHA; 25% HAHs; and 2.2% HsHs (die young)

Malaria not present AA advantage99.999% HAHA; 0.001% HAHs; and 0% HsHs

With malaria, balancing selection for the heterozygote Without malaria, directional selection for HAHA

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

Codon Bias

In the case of amino acids

Mutations in Position 1, 2 lead to Amino Acid change

Mutations in Position 3 often don’t matter

(1) Simplest Test: Ka/Ks Test

Nonsynonymous substitution rate Ka

Synonymous substitution rate Ks

Need coding sequence (sequence that codes proteins)

Ks is used here as the “control”, proxy for neutral evolution

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

> 1

(1) Ka/Ks Test

Nonsynonymous substitution rate Ka

Synonymous substitution rate Ks

In the absence of selection, you’d expect Ks = Ka, and for Ka/Ks = 1

A greater rate of nonsynonymous substitutions (Ka) than synonymous (Ks) is used as an indication of positive selection (Ka/Ks >1)

If Ks > Ka, or Ka/Ks < 1, that would suggest purifying selection, that selection might be preserving amino acid composition

> 1

Summary

(1) Of the evolutionary forces that can disrupt HW Equilibrium, Natural Selection is the only one that is adaptive

(2) Selection occurs through differential reproduction which is NOT random

(3) Natural selection requires genetic variation upon which it can act

(4) There are different ways in which selection can act (favoring the extremes, or heterozygotes, or unidirectional)

Concepts

Natural SelectionFitnessDirectional,Stabilizing,Disruptive SelectionBalancing SelectionSelection on dominant

vs recessive alleles

The following are numbers of red, pink, and white flowers in a population.

(A1A1) (A1A2) (A2A2)Red Pink White

Generation 1: 400 200 400Generation 2: 600 100 300Generation 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) A1: 0.50, A2: 0.50

A1A1: 0.25, A1A2: 0, A2A2: 0.25

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

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) (C) Selection acts on genetic variation such as

Mutations(D) Selection acts on differential fitness of genetically

distinct offspring(E) Evolution occurs at the level of the individual

Answers:

1B2C3E4D

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Natural Selection