Lectures by Kathleen FitzpatrickSimon Fraser University

Copyright © 2012 Pearson Education Inc. Mark F. Sanders John L. Bowman

G E N E T I CA N I N T E G R A T E D A P P R O A C H

A N A LY S I S Chapter 22Population Genetics and

Evolution

Alleles

• Punnet squares will track alleles to an individuals

• How about populations?

Populations and Gene Pools

• A population is a group of interbreeding organisms

• A gene pool is the collection of genes and alleles found in the members of a population

• The pattern of mating between individuals determines how alleles are dispersed into genotypes, and their frequencies in successive generations

http://www.bjupress.com

The Hardy-Weinberg Equilibrium Describes the Relationship of Allele and

Genotype Frequencies in Populations• Godfrey Hardy showed that with random mating and the absence

of evolutionary change, allele frequencies result in a stable equilibrium frequency

• Wilhelm Weinberg independently came to a similar conclusion; the result is the Hardy-Weinberg (H-W) equilibrium, named after both of them

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The Hardy-Weinberg Equilibrium

• The simplest predictions of H-W equilibrium involve two alleles of an autosomal gene, A1 and A2

• The frequencies for these are given as f(A1) p and f(A2) q, with equal frequencies in males and females

• Since there are only two alleles of the gene, p q 1.0

• For the two alleles, there are three possible genotypes: A1A1, A1A2, and A2A2

Genotype Frequencies

• The genotype frequencies can be computed using the binomial expansion (p q)2

• The two p q terms represent male and female contributions to mating

• The summation of the genotype frequencies is p2 2pq q2 1.0, where

– p2 frequency of A1A1

– 2pq frequency of A1A2

– q2 frequency of A2A2

What is the genotype probability?• In a hypothetical population, the allele A1

occurs 40% of the time and the A2 allele occurs 60% of the time. What is the probability of each of the genotypes in the first generation?

What is allele frequency of the NEXT generation following the first?

Allele frequencies do not change from one generation to the next!Allele frequencies do not change from one generation to the next!

The Hardy – Weinberg equilibrium for two autosomal alleles

Random Mating

• Random mating for one generation produces genotype frequencies that can be predicted from allele frequencies

• For any frequency of p and q, an expected equilibrium distribution of genotypes can be derived

• With random mating and no evolutionary change, these frequencies will remain constant from one generation to the next

http://disneynumber1fan.deviantart.com/art/Random-Mating-OPEN-350760430

If the genotypes are not the same, we must x2 to account for reciprocal matings

One generation of random mating will produce a population in HW equilibrium

One generation of random mating will produce a population in HW equilibrium

Determining Autosomal Allele Frequencies in Populations

• Documentation of allele frequency changes over time is a hallmark of population evolution

• Three equally valid methods can be used to determine allele frequencies of autosomal genes in populations• The Genotype Proportion Method• The Allele-Counting Method• The Square Root Method

The Genotype Proportion Method• Can be used to determine allele frequencies whether or not a population is in equilibrium• It requires that the genotypes of all members is known

• Major limitation

• Each homozygote frequency is added to half the heterozygote frequency to determine p and q

• B1B1 = 0.64, B1B2 = 0.32, B2B2 = 0.04

• What is ƒ(B1)?

The Allele Counting Method

• The allele counting method can also be used whether or not a population is in H-W equilibrium

• It requires that the genotypes of all members is identifiable based on phenotype, and so is feasible in cases where alleles are codominant

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Blood group M MN NNumber 406 744 332 = 1482

What is the frequency of M and N?What is the frequency of M and N?

The Square Root Method• The square root method can only be used if a population is in H-W

equilibrium• One allele must be recessive (a disease allele)• q is calculated as the square root of the frequency of the

homozygous recessive class, and then p is simply calculated as 1.0 q

• In the US, cystic fibrosis occurs in 1 in 2,000 newborn infants. What is the frequency of the disease allele?

How many people are carriers?

The Hardy-Weinberg Equilibrium for More Than Two Alleles

• H-W equilibrium values can be determined for more than two alleles, e.g., in the case of three alleles, such as the ABO blood type alleles

• The allele frequencies are p, q, and r

• In this case, p q r 1.0 and the allele frequencies are calculated by the trinomial expansion: (p q r)2

• The six possible genotypes are predicted by p2 2pq q2 2pr r2 2qr 1.0

Testing the Hardy-Weinberg Prediction

• The assumptions of H-W equilibrium are unattainable in real populations

• How do we determine if observed genotype frequencies in populations are significantly different from those predicted by H-W equilibrium?

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Practice Problems!

• Friendly Reminder! Even numbered problems at the end of the Chapter have answers in the back of the book

• Do problems 10, 18, 19, 20, 21• Will get answers for 19 & 21 in review session

24ANIMATION: Population Genetics-1

25ANIMATION: Population Genetics-2

26ANIMATION: Population Genetics-3

27ANIMATION: Population Genetics-4

Calculating Genotype Frequencies for X-Linked Genes Using the Hardy-

Weinberg Equilibrium

• The pattern of transmission of X-linked genes differs from that of autosomal genes because males are hemizygous

• Males inherit their X chromsome from the their mothers and transmit their X chromosome exclusively to their daughters.

Determining Frequencies for X-Linked Alleles

• For X-linked genes with two alleles, A1 and A2, females have three possible genotypes: A1A1, A1A2, and A2A2

• Males are hemizygous and so have only two possible genotypes, A1Y or A2Y

• Therefore, p and q can be easily estimated as p f(A1Y) and q f(A2Y)

• Female genotypes should be seen in the frequencies: p2, 2pq, and q2

Example: Red-Green Color Blindness

• Red-green color blindness is an X-linked recessive trait that affects about 9 percent of human males

• What is the expected frequencies of homozygous normal, heterozygous, and color-blind females?

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Hardy-Weinberg Equilibrium for X-Linked Genes

• Allele frequencies in males and females are stable as long as random mating takes place.

• For X-linked genes, a single generation of random mating does not achieve equilibrium; several generations are required

• Due to sex-dependent differences in transmission of X-linked genes, the male frequencies will be the same as the female frequencies in the previous generation Males transmit their X alleles

exclusively to their daughters!

Practice Problem

• Question 24

22.3 Natural Selection Operates Through Differential Reproductive

Fitness Within a Population• H-W equilibrium is maintained when there is no evolutionary change in a

population

• However, allele frequencies do change when evolution occurs

• The evolutionary impact can be calculated as long as the effect on allele frequency can be estimated

Differential Reproductive Fitness and Relative Fitness• Natural selection favors certain phenotypes

• Anatomical• Physiological• Behavioral traits

• Leads to increased reproductive success of individuals with certain phenotypes: differential reproductive fitness

• Quantified using relative fitness (w), and organisms with the highest reproductive success are assigned a value of w 1.0

• Individuals that reproduce less successfully have their relative fitness decreased by a proportion called the selection coefficient (s) w = 1 - s

Directional Natural Selection

• In directional natural selection, one phenotype has a higher relative fitness than other phenotypes• acts to increase the frequency of the favored allele over the

others

1. What is the selection coefficient for the heterozygotes?

2. How many survivors of each genotype in the next generation?

3. What are the allele frequencies in the next generation of survivors?

1. What is the selection coefficient for the heterozygotes?

2. How many survivors of each genotype in the next generation?

3. What are the allele frequencies in the next generation of survivors?

40

1. Survivors of each genotype:

B1B1 (1.0)(360) 360

B1B2 (0.80)(480) 384

B2B2 (0.40)(160) 64

2. Allele frequencies next generation:

f(B1) [(2)(360) (384)]/1616 0.683

f(B2) [(2)(64) (384)]/1616 0.317

808 of the original 1,000 organisms remain after natural selection!

808 of the original 1,000 organisms remain after natural selection!

Directional Natural Selection Over Time• Directional natural selection will increase the frequency of certain

alleles with variable intensity, depending on the strength of selection• Greater selection strength the greater the difference in relative fitness

frequencies

• Progression toward fixation, i.e., where f(B1) 1.0 is more rapid with strong selection and very slow when selection is weaker

• The strongest selection occurs when one genotype has w 0.0• What does this mean?

Startƒ(B1)= 0.01ƒ(B2)= .99

Startƒ(B1)= 0.01ƒ(B2)= .99

Natural selection is strongest when the natural selection differences between the genotypes is larger!

Natural selection is strongest when the natural selection differences between the genotypes is larger!

Allele frequency change is slow when allele frequencies are low and faster when alleles numbers are higher

Allele frequency change is slow when allele frequencies are low and faster when alleles numbers are higher

Directional Natural Selection; Progression to Fixation

• Directional natural selection against organisms with the recessive phenotype will cause the frequency of the dominant allele to increase and the recessive to decrease

• Eventually the recessive allele may be completely eliminated

• However, this can be a slow process, as heterozygous individuals will still carry the recessive allele

25% of the population will be removed this generation!

25% of the population will be removed this generation!

Population starts with 50% B and 50% b

Big change in allele frequencies

Still going to make bb!

Laboratory Experiment on Directional Selection

• Cavener and Clegg examined four subpopulations of Drosophila for 50 generations to test the effects of directional selection in increasing the frequency of the allele AdhF (Adh–alcohol dehydrogenase)

• The original population had AdhF allele frequency of 0.38

• Two subpopulations were reared on ethanol-rich food, and two on food without ethanol

Natural Selection Favoring Heterozygotes

• Balanced polymorphism: allele frequencies are maintained by selection against either homozygote

• E.g., individuals who are heterozygous for the sickle cell anemia allele, AS, resistant to malaria, such that heterozygotes in regions where malaria is prevalent are favored over either homozygote

Malaria: Plasmodium that infects RBCs

Example: Model for Natural Selection Favoring Heterozygotes

• Malaria Example:• Suppose relative fitness of Cc individuals is 1.0, of CC is

0.80, and of cc is 0.20• In generation 0, the allele frequencies are both 0.50

• What are the allele frequencies after a single generation?

• What will the genotype frequencies be after reproduction?

The recessive allele will decrease in frequency relative to the dominant, but will not be eliminated

Total: 0.75

50ANIMATION: Population Genetics-5

22.5 Migration• Migration refers to the movement of organisms between

populations and thus genes flowing between populations

• Migration is also known as gene flow and the new population is called an admixed population

Effects of Gene Flow• Gene flow has two principal effects on population:

• In the short run, gene flow can change allele frequencies in the admixed population

• In the long run, gene flow acts to equalize frequencies of alleles between populations that remain in genetic contact• Can slow genetic divergence and block speciation

Island Model of Migration

• The admixed population has an immediate evolutionary change in allele frequencies, but will not be in H-W equilibrium at first; this requires one generation of random mating

Immediate effect

Single generation mating brings alleles into HW equilibrium

22.6 Genetic Drift Causes Allele Frequency Change by Sampling Error

• Genetic drift refers to chance fluctuations of allele frequencies that result due to sampling error• Genetic drift occurs in all populations but is especially

prominent in small populations

http://evolution.berkeley.edu/evosite/evo101/IIID1Samplingerror.shtml

50/50 start50/50 start Draw6:4

Draw7:3

Draw4:6

Population random fluctuating around tan/green

By chance an allele can be fixed or eliminated

The number of generations is takes to do this can vary

Genetic Drift

The Founder Effect

• Establishment of a new population by a small number of founding organisms can produce a difference in allele frequencies, and is called the founder effect

• The allele frequencies of the new population may differ from the original population as a result of sampling error

The Founder Effect and Genetic Disorders

• 1700s: the Old Order Amish in Pennsylvania were established by a founding population of about 200

• They exhibit high frequencies of autosomal and X-linked recessive disorders that are rare in the populations of origin (European) and the nearby non-Amish populations

• Ex. Ellis-van Crevald Syndrome:

• Autosomal reccessive

• Short stature, short forearms, extra digits on hands and feet

Genetic Bottlenecks

• In genetic bottlenecks, a relatively large population is reduced to a very small number by a catastrophic event unrelated to natural selection

• Survivors of the bottleneck likely have a low level of genetic diversity and usually carry alleles in very different frequency than the original population

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22.7 Nonrandom Mating Alters Genotype Frequencies

• Nonrandom mating upsets H-W equilibrium• Nonrandom mating patterns:

• Inbreeding, mating between related individuals• positive assortative and negative assortative mating with

respect to specific phenotypes mating together

Inbreeding• Inbreeding, also called consanguinous

mating, is mating between gentically related individuals• Consanguinous = ‘with blood’

• Mates will share a greater proportion of alleles with one another than random members of a population

• Consequence of inbreeding:• an increase in the frequency of homozygous

genotypes• decrease in the frequency of heterozygous

genotypes

Self-Fertilization

• Inbreeding, for self-fertilizing plants and some self-fertilizing animals, is a normal reproductive process

• Assuming that the starting parent is heterozygous, subsequent self-fertilization leads to a decrease in heterozygous frequency by one-half in each generation

• The allele frequencies remain the same; but genotype frequencies change each generation

http://facstaff.uww.edu/tipperyn/reprodbio/index.htm

Allele frequencies remain at ƒ(A1) = ƒ(A2) = 0.50

Inbreeding in Mammalian Populations

• First-cousin mating is relatively common in some human societies and is common in mammals in general (10% worldwide)• Uncommon in US

• First cousin matings results in in infants with homozygous recessive conditions at a higher frequency than expected in the general population

• If a recessive allele is more frequent in a population, chances of a recessive homozygote in a first-cousin mating is only a few times more likely than in random mating

Charles Darwin Emma Darwin

Inbreeding Depression

• The genetic consequences of inbreeding for populations is an increase in the frequency of homozygous genotypes

• Inbreeding depression is the reduction of fitness of inbred organisms due to the reduced level of heterozygosity

• Among plants that reproduce by self-fertilization, inbreeding depression is low, whereas among mammals, it can be severe

Assortative Mating• When mates of similar phenotype

choose one another, it is known as positive assortative mating; mates of dissimilar phenotype undergo negative assortative mating

• Positive assortative mating differs from inbreeding in being focused on phenotype rather than “relatedness”

• In both cases, the effect is limited to the genes that influence the phenotype and its impact on the overall population is limited by the mating that is otherwise random

Assortative Mating in Humans

• Positive Assortative Mating:• Height• Skin color• IQ• Dwarfism

– Negative Assortative Mating:• Redheads

22.8 Species and Higher Taxonomic Groups Evolve by the Interplay of

Evolutionary Processes• Evolutionary change at the

species level and above is driven by reproductive isolation that can result from any conditions that prevent one population from mating with others• Morphological• Behavioral• Geographical

– Isolated populations adapt to their particular circumstances, leading to divergence and speciation

Ex. Fruit flies & food preference?

http://evolution.berkeley.edu/evolibrary/article/evo_44

Speciation

• Charles Darwin (1859, On the Origin of Species by Means of Natural Selection) laid out two guiding principles of speciation:• Hereditary variation exists in

all species and controls phenotypic variability, passed from parent to offspring

• Natural selection allows for increased survival and reproduction in individuals with favored phenotypic attributes

Processes of Speciation

• What speciation is NOT:• Simple, straight line of descent• Organized plan to evolve to the

‘most advanced species’

• Evolutionary history resembles a multibranched bush

NO:

YES!

Evolution of the genus Equus

The lineage of horses and their relatives the zebras and donkeys can be traced from the early Eocene (54 million years ago) to present, but there are numerous branches of the lineage that did not produce modern-day organisms

Construction of Evolutionary Trees• Equus tree reconstructed using

fossil evidence• Genetic reconstruction:• DNA isolated from Neandertal

bones in E. Europe.– Fragmentary, but provided a nearly

complete sequence determination of a Neandertal genome

– At present, 6 genomes have been found

– 2012: Neandertal DNA sequences present in genomes of human indigenous to Europe and Asia, but not Africa (not present)

– 2-4% of modern human DNA has Neaderthal origin

Reconstruction of the head of the Shanidar 1 fossil, a Neanderthal male who lived c. 70,000 years ago (John Gurche 2010

Patterns of Speciation

• The evolutionary tree of Equus illustrates two patterns of speciation:

• Anagenesis is the process by which an original species is transformed into a different species over many generations

• Cladogenesis is a pattern of branching in which an ancestral species gives rise to two or more new species

http://biology-forums.com/index.php?action=gallery;sa=view;id=710

Evolution of the genus Equus

The lineage of horses and their relatives the zebras and donkeys can be traced from the early Eocene (54 million years ago) to present, but there are numerous branches of the lineage that did not produce modern-day organisms

Reproductive Barriers and Speciation

• Anagenesis and cladogenesis share features: • Inherited genetic variation

controlling phenotype• Adaptation through natural

selection• Reproductive isolation

• Reproductive barriers that prevent exchange of genes between populations may be prezygotic or postzygotic

http://evolution.berkeley.edu/evosite/evo101/VSpeciation.shtml

Reproductive Barriers

• Prezygotic mechanisms of reproductive isolation prevent mating between members of different species or the formation of a zygote following interspecies mating

• Postzygotic mechanisms result in failure of a fertilized zygote to survive, or survival of but sterility of the individual produced Male donkey + female horse = Mule

63 chromosomes (62 donkey, 64 horse)STERILE

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Allopatric Speciation

• Allopatric speciation occurs when populations are separated by a physical barrier and thus develop in separate geographic locations or environments• Physical barrier between two segments of a population (glacier,

mountain range, canyon)• colonization of a new territory by some members of a

population

jobspapa.com

Diversification of Drosophila Species on Hawaiian Islands

• Hundreds of species of Drosophila inhabit the Hawaiian Islands, which were formed volcanically

• The most closely related species are found on adjacent islands, and the phylogenetic pattern of species origin corresponds to the emergence of islands

http://evolution.berkeley.edu/evosite/evo101/VBDefiningSpeciation.shtml

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Sympatric Speciation

• In sympatric speciation, population genetics or postzygotic mechanisms prevent gene flow between the two populations, that are not physically separated• Genetic mechanisms or postyzygotic

mechanisms that prevent successful interbreeding

• Some prezygotic mechanimsism: behavioral, seasonal, or other processes that limit opportunities for interbreeding

• For example, animals that develop nocturnal or diurnal patterns of activity are most likely to mate with others with the same pattern

Ex.: Male frog call no longer attracts the female

Sympatric Speciation; Polyploidy• A clear example of sympatric speciation occurs in plant species that diverge

through the development of polyploidy

• Mating between a polyploid species and a nonpolyploid one can result in reduced fertility of hybrid offspring

Questions?