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Chapter 6

The ways of change: drift and selection Population genetics

Study of the distribution of alleles in

populations and causes of allele frequency

changes

Key Concepts

Diploid individuals carry two alleles at every

locus

Homozygous: alleles are the same

Heterozygous: alleles are different

Evolution: change in allele frequencies from

one generation to the next

Hardy-Weinberg equilibrium

Population allele frequencies do not change

if:

Population is infinitely large

Genotypes do not differ in fitness

There is no mutation

Mating is random

There is no migration

Predictions from Hardy-Weinberg

Allele frequencies predict genotype frequencies

p2 + 2pq + q2 = 1

Key Concepts

Hardy-Weinberg theorem proves that allele

frequencies do not change in the absence of

drift, selection, mutation, and migration

Mechanisms of evolution are forces that

change allele frequencies

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Populations evolve through a variety

of mechanisms Key Concept

Hardy-Weinberg serves as the fundamental

null model in population genetics

Genetic Drift

Peter Buri started 107 cultures with 8 males and 8

females all heterozygous for bw75 red eye and for bw

white eye

bw / bw75 heterozygous orange parents

All H-W assumptions met except large population size

19 generations – each generation started with:

Randomly selected: 8 males and 8 females

Many populations had alleles that went to

Extinction

Fixation Other populations ranged between two extremes

What happened?

Genetic drift causes evolution in finite

populations

Genetic drift causes

evolution in finite

populations

Genetic drift results from random

sampling error

Sampling error is higher with smaller sample

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Drift reduces genetic

variation in a population

Alleles are lost at a faster

rate in small populations

Alternative allele is fixed

Key Concepts

Genetic drift causes allele frequencies to

change in populations

Alleles are lost more rapidly in small

populations

Evolutionary biologists have debated the

importance of natural selection and

genetic drift

R.A. Fisher

Natural Selection

and

Statistics

Sewel Wright

Genetic Drift

Important

Motoo Kimura

also emphasized

Genetic Drift

Bottlenecks reduce genetic variation Northern Elephant Seals – killed for tusks (ivory)

and then for museums!

A bottleneck causes genetic drift

Rare alleles are most likely to be lost

during a bottleneck Founder Effect Mutiny on the Bounty –Pitcairn Islands

Founder effects cause genetic drift

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High incidence of migraine headaches

attributed to founder effects on Norfolk Island

in Pitcairn Islands

Genotypes, Phenotypes and

Selection

Alleles are selectively neutral if they have no

effect on the fitness of their bearers. This

phenomenon often occurs when genetic

variation at a locus does not effect the

phenotype of an individual.

Selection acts on whole phenotypes of

individuals.

Key Concept

Even brief bottlenecks can lead to a drastic

reduction in genetic diversity that can persist

for generations

Key Concept

Alleles are selectivity neutral if they have no

effects on the fitness of their bearers. This

phenomenon often occurs when genetic

variation at a locus does not affect the

phenotype of an individual.

Selectively neutral

S = selection coefficient used to express how

much genotypes differ in fitness

Selection acts on whole phenotypes of

individuals So must affect fitness

The concept of fitness

Fitness: the reproductive success of an individual with a particular phenotype

Components of fitness:

Survival to reproductive age

Mating success

Fecundity

Relative fitness: fitness of a genotype standardized by comparison to other genotypes

Selection Changes Allele Frequencies

Average excess fitness: difference between

average fitness of individuals with allele vs.

average fitness of those without

Use this to predict how the frequency of the

allele will change from one generation to the

next

Change in frequency

due to selection p is

frequency of A1 allele

Average fitness of the

population p is frequency of A1

allele

Average excess of fitness

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Natural selection more powerful in

large populations

Drift weaker in large populations

Selection weaker in small populations

Small advantages in fitness can lead to large

changes over the long term

Pleiotropy may constrain evolution

Pleiotropy: mutation in a single gene affects

many phenotypic traits

Can be antagonistic

Net effect on fitness determines outcome of

selection

Pesticide resistance and pleiotropy

• Ester1 - mosquitoes resistant to insecticide, but more vulnerable to

spider predation. Ester1 higher fitness on coast; away from coast much

lower fitness (no insecticide)

• Ester+4 less protection from mosquitoes at coast, but more common

than Ester1.. Higher fitness inland because less cost of predation. BUT

higher costs due to overproduction of esterases.

• Antagonistic Pleiotropy

Pesticide resistance and pleiotropy

Antagonistic Pleiotropy

Effects of mutation have opposite effects on

fitness

Ester1 has benefit along the coast but

Inland, benefit declines because there are

fewer mosquitoes, and cost increases due to

increased chance of predation by spiders

Key Concept

Hardy-Weinberg serves as the fundamental

null model in population genetics

Condition that we try to falsify

Test populations to see if they are in H-W equil.

These are the null model frequencies

Ex: Hemoglobin (Box 6.3)

Cavalli-Sforza - Nigeria

Hg A and S (based on difference in β-globin)

Results: More SA and AA and fewer SS than

H-W would predict

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Why are there so many hemoglobin

A alleles in the population?

Heterozygote Advantage

S = sickle cell disease hemoglobin

SS = sickle cell disease

Low fitness

A = normal hemoglobin

AA = Susceptible to malaria

Low fitness

AS

Protected from malaria

Protected from sickle cell disease

Survive and reproduce – higher fitness

Testing the Null Model

Cavalli-Sforza, 2007

Heterozygote advantage and sickle-

cell anemia Founder effect

Amish of Lancaster, PA

Ellis-van Creveld Syndrome:

mutation causes dwarfism

and polydactylism

General population at levels

less than 0.1%,

Lancaster Amish the allele’s

level is approximately 7%.

Absence of upper

incisors and conical

lower incisors

Ellis-van Creveld

Inherited disorder of bone growth:

Very short stature (dwarfism).

Short forearms and lower legs

Narrow chest with short ribs.

Extra fingers and toes (polydactyly),

Malformed fingernails and toenails

Dental abnormalities.

More than half of affected individuals are born

with a heart defect, which can cause serious

or life-threatening health problems.

Founder effect

Nonrandom Mating

sibling matings - Inbreeding

reduces variation

Fig Wasps

Naked Mole rats

Human Eyebrow Mites

(Demodex folliculorum)

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Experimental evolution

provides important

insights about selection

• Richard Lenski started 1988

• Started culture with 1 E. coli cell

• Started 12 cloned populations

• Grow in 10 mL cultures with

small amount of glucose

Natural selection in action

Alleles that lower fitness experience Negative Selection

Alleles that increase fitness experience Positive Selection

Results

All cultures adapted to low glucose availability

Accumulated adaptations that made them

more efficient at growing under the

experimental conditions

Rate of increase in fitness has slowed but still

condinues to rise after 60K generations

Comparison of wild and adapted

strains

Transfer segments of DNA from one cell of

generation 10K into ancestral cultures of the

same line

Then mixed each line of engineered bacteria

with unmanipulated ancestral bacteria

Results:

Saw increased fitness with one particular

engineered line DNA segment

Help synthesize cell membrane

Transferred one nucleotide into ancestral

bacteria and increased fitness by 5%

Comparison of wild and adapted

strains

Tested generation 500 for mutation – not

present

Tested generation 1000 and found that

mutation was present in 45% of population

Generation 1500 97% of bacteria had it

This rapid spread is typical of a mutation that

enhances fitness

Mutation may allow cell to make thinner

membranes while reproducing faster

Found epistatic genes (interact with other

alleles)

Relationships among alleles at a locus

Additive: allele yields twice the phenotypic

effect when two copies present

Especially vulnerable to selection

Favorable alleles can go to fixation if additive

allele is present

Fitness order: Heterozygotes – homozygotes –

those without the allele

Deleterious alleles can go extinct

Fitness order:– homozygotes -those without the

allele – heterozygotes - homozygotes with the

allele

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Relationships among alleles at a

locus

Dominant and recessive alleles are not

additive

Dominance: dominant allele masks presence

of recessive allele in heterozygote

Dominant allele has same effect whether

present in one or two copies

Effects of selection on different types

of alleles

Mutation generates variation

Mutation rates for any given gene are low

But, considering genome size and population

size many new mutations arise each

generation

Estimate in humans: 8.5 billion new mutations

Source of variation for selection and drift to

act on

Mutation-selection balance

Equilibrium frequency reached through tug-

of-war between negative selection and new

mutation

Explains persistence of rare deleterious

mutations in populations

Balancing selection

Some forms of selection maintain diversity in

populations:

Negative frequency-dependent selection

Fitness is high when phenotype is rare

Fitness is low when phenotype is common

Heterozygote advantage

Negative frequency-dependent

selection

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Key Concepts

Selection occurs when genotypes differ in

fitness

Outcome of selection depends on frequency

of allele and effects on fitness

Population size influences power of drift and

selection

Drift more powerful in small population

Selection more powerful in large population

Key Concepts

Alleles may have pleiotropic effects

When fitness effects oppose each other

environment determines direction of selection

Laboratory evolution studies reveal how

alleles rise and spread through populations

Rare alleles almost always carried in a

heterozygous state

Recessive alleles invisible to selection

Selection cannot drive dominant to fixation

Key Concepts

Mutations are the source of new genetic

variation in populations

Can be many in a large population

Balancing selection maintains multiple alleles

in populations

Negative frequency-dependent

Heterozygote advantage

Inbreeding and the Hapsburg dynasty

Inbreeding coefficient

Probability that two alleles are identical by descent

Inbreeding depression results in reduced

fitness- inbreeding and selection

Rare deleterious alleles more likely to combine

in homozygotes

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Key Concepts

Alleles are identical by descent if they both

descended from a single mutational event

Inbreeding increases percentage of loci that

are homozygous for alleles identical by

descent

Genetic bottlenecks often go hand in hand

with inbreeding and selection

Recessive alleles exposed to selection

How Genetic Variation is Lost

Effects of Population size

Genetic Drift: fixation or loss of alleles

Population bottlenecks

causes

habitat destruction or fragmentation

introduced competitors or predators

disease

affects Mendelian (discontinuous) characters

more severely than quantitative (continuous)

characters

Genetic Drift

ex. Cheetahs Acinonyx jubatus

Large scale climate change about 10,000 years ago

Most populations of cheetahs went extinct in North America,

Europe, Asia, and much of Africa

Current animals are the result of inbreeding among the

surviving few animals (perhaps a single preganant female?)

Little genetic variability especially among immune system

genes

Genetic Drift

Habitat encroachment and poaching have

further reduce cheetah numbers,

consequently snuffing out even more genetic

variation and leaving cheetahs even more

vulnerable to extinction.

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10,000ya

Slides excerpted from:

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Cheating Cheetahs

2007 study, female cheetahs seem to be at least as

promiscuous as their male counterparts.

Females frequently mate with several different

males while they are fertile and are then likely to

bear a single litter of cubs fathered by multiple

males making many of the cubs within a single

litter only half-siblings.

This discovery has important implications for the

conservation of these endangered animals.

Though it conflicts with the idea that cheaters

never prosper, evolutionary theory suggests

that, in this case, cheating may be beneficial

Cheating Cheetahs

Three hypotheses for evolution of cheating

1. Even if several of her cubs were killed by a new

disease, succumbed to a novel environmental

stress, or just didn't have what it took to make a

living in the Serengeti, a female with a variable litter

could still hope that one of her cubs would have "the

right stuff" to survive.

Biologists refer to this as "bet-hedging" — not

putting all your eggs (or in this case, cubs) in one

basket.

Cheating Cheetahs

2. Perhaps, multiple mating is really a strategy to avoid

expending extra energy fending off would-be

suitors. In other words, maybe females mate

multiple times not because it ensures genetic

variation in offspring, but because it's so much

easier than fighting off males right and left.

Web info from Berkeley evolution education site

http://evolution.berkeley.edu/evolibrary/news/07070

1cheetah

Cheating Cheetahs

3. Perhaps multiple mating evolved as a way to deter

infanticide. In some big cats (and in many other species),

males try to kill cubs that are not their own. However, if a

mother mates with many different males, it is more difficult

for a male to tell whether or not a cub is his own — and the

male would likely be deterred from killing the cub. This third

hypothesis suggests that multiple mating was favored by

natural selection because it discouraged infanticide against

a female's cubs, not because it increased the litter's genetic

variation.

This third hypothesis fits with the observation that wild

cheetah males seem to rarely (if ever) commit

infanticide, though it is common in lions and other big

cats.

Cheating Cheetahs

Gottelli, D., Wang, J., Bashir, S., and Durant, S. M.

(2007). Genetic analysis reveals promiscuity among

female cheetahs. Proceedings of the Royal Society B

274(1621):1993-2001.

http://dx.doi.org/10.1098/rspb.2007.0502

Menotti-Raymond, M., and O'Brien, S. J. (1993). Dating

the genetic bottleneck of the African cheetah.

Proceedings of the National Academy of Sciences

90(8):3172-3176.

http://www.pnas.org/content/90/8/3172.abstract

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Natural Selection

Individuals vary in the expression of their

phenotypes

This variation causes some individuals to

perform better than others

Natural Selection happens when there is

differential fitness

Modern definition: Natural Selection

The differential survival or reproduction, on the

average, of different phenotypes in a population

Will lead to changes in frequencies of those

phenotypes within a generation, that is,different

age classes will have different phenotype

frequencies.

Within a generation - Darwin thought of many

generations

Evolution happens between generations

Note: NS does not have to lead to evolution!

The concept of fitness

Fitness: the reproductive success of an individual with a particular phenotype Ability to get genes into future generations

Components of fitness: Survival to reproductive age

Mating success

Fecundity

Relative fitness: fitness of a genotype standardized by comparison to other genotypes

Measuring Fitness

Difficult, rarely possible to

Record lifetime reproductive success

Record how many of those offspring survive to

reproduce themselves

Other problems

Can’t follow organisms for long time

Complex relationship b/w genotype and phenotype

Fitness is product of entire phenotype

Proxies for fitness

Probability of surviving to reproductive age

Measure number of offspring in a season

Fitness

t and t+1 = generations

Fecundity = ability to produce gametes

Contribution to the next generation = fitness

If different phenotypes are due to different genotypes,

and have different fitnesses, then natural selection

will act and the phenotype and genotype frequencies

will change.

Zygote adult gametes zygotes

t t t t+1

Survival Fecundity Mating

Fitness

Absolute fitness of a genotype = average

reproductive rate of individuals with that genotype

Absolute Fitness = W

Subscripts = genotypes

A1A1 W11

A1A2 W12

A2A2 W22

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Fitness

Absolute fitnesses determine whether a population

will increase or decrease in size

If average absolute fitness of all individuals in the

population is >1 then population increases in size

If average absolute fitness is <1 then population

decreases in size

Fitness

Population geneticists use value W

W = all fitness components: survival, mating

success and fecundity

Describes relative contribution of individuals

with one genotype compared with the average

contribution of all individuals in the population

Relative Fitness

Average excess fitness: difference between

average fitness of individuals with allele vs.

those without Δp = p x (aA1/ϖ)

Contribution of alleles to fitness

Average excess fitness can be used to

predict how the frequency of the allele will

change from one generation to the next