Chapter 6: Mendelian Genetics in Populations I ...
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
Chapter 6: Mendelian Genetics in Populations I- Selection and Mutation as Mechanisms of Evolution 5.4| Measuring Genetic Variation in Natural Populations How Much Genetic Diversity Exists in a Typical Population • Early efforts to study allelic diversity in populations were based on allozyme electrophoresis • Isolating proteins from a large sample of individuals, separating the proteins in an electrophoresis gel, and then staining the gel to visualize the proteins produced by a particular gene • If alleles in a population were different enough that their proteins products had different sizes or charges, then proteins would migrate differently in the gel and would show up as different bands • Demonstrated that most natural populations have substantial genetic varation • Not as accurate • Recent studies have shown that in most populations, many alleles are present at every gene in the genome. Genetic variation is extensive • Genetic diversity is maintained by natural variation
6.1| Mendelian Genetics in Populations: The Hardy-Weinberg Equilibrium Principle • •
Population genetics begins with a model of what happens to allele and genotype frequencies in an idealized population Once we know how Mendelian genes behave in the idealized population, we will be able to explore how they behave in real populations
A Stimulation • Gene pool: the set of all copies of all alleles in a population that could potentially be contributed by the members of one generation to the members of the next generation • Starting with the eggs and sperm that constitute the gene pool, our model traces alleles through zygotes and adults and into the next generation’s gene pool • When the alleles frequencies from the start are different from the end of the generation, then the population has evolved • Genetic Drift: change in frequencies of alleles in a population resulting from sampling error in drawing gametes from the gene pool to make zygotes and from chance variation in the survival and/or reproductive success of individuals; results in nonadaptative evolution A Numerical Calculation • Punnett squares can be used to predict genotypes of offspring by making crosses between two heterozygotes • Can also calculate genotype frequencies among the zygotes by multiplying allele frequencies
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
The Hardy Weinberg equilibrium principle yields two fundamental conclusions 1. The allele frequencies in a population will not change, generation after generation 2. If the allele frequencies in a population are given by p and q, then genotype frequencies will be given by p2, 2pq, q2 Hardy Weinberg Assumptions 1. There is no selection. • All members have survival at equal rates and contribute equal numbers of gametes to the gene pool (equal reproductive success) • When violated: the frequencies may change from one generation to the next 2. There is no mutations • No copies of existing alleles were converted by mutation, no new alleles created • When violated: some alleles with higher mutations rates, allele frequencies may change from one generation to the next 3. There is no migration • No individuals moved into or out of the model population' • When violated: individuals carrying some alleles move into or out of the population at higher rates than individual carrying other alleles, allele frequencies may change from on e generation to the next 4. There are no chance events • No genetic drift, and the model population is indefinitely large • When violated: if some individuals contribute more alleles to the next generation than others, allele frequencies may change from one generation to the next 5. Mating is random • When violated: genotype frequencies may change. Shifts in genotype frequency and in combination of the other 4 assumptions, can influence the evolution of populations
6.2| Selection • • •
Selection happens when individuals with particular phenotypes survive to reproductive age at higher rates than other phenotypes Or when individuals with particular phenotypes produce more offspring during reproduction than individuals with other phenotypes Selection can lead to evolution when phenotypes that exhibit difference in reproductive success are heritable
Adding Selection to the Hardy-Weinberg Analysis: Changes in Allele Frequencies • Selection can cause allele frequencies to change across generations • Violation of the no-selection assumption has resulted in violation of conclusion 1 of the Hardy-Weingberg analysis • The numerical examples shows that when individuals with some genotypes survive at higher rates than individuals with other genotypes, allele frequencies can change from one generation to the next • Natural selection causes change in allele frequencies, causes evolution • Fig 6.12
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
Each curve shows the change in allele frequency over time under a particular selection intensity Adding Selection to the Hardy-Weinberg Analysis: The Calculation of Genotype Frequencies • Selection can change genotype frequencies so that they cannot be calculated by multiplying the allele frequencies • Natural selection can also drive genotype frequencies away from the values predicted under the Hardy-Weinberg equilibrium principle • In this experiment, there was a strong natural selection for homozygotes • Genotype frequencies have changed among the adult survivors • Violation of the no-selection assumption has resulted in violation of conclusion 2 • The discovery that genotype frequencies in a population are not in HW equilibrium may be a clue that natural selection is at work o
6.3| Patterns of Selection: Testing Predictions of Population Genetic Theory Selection on Recessive and Dominant Alleles • Fig 5.16 • The curves predict that evolution will be rapid at first but will slow as the experiment proceeds • Dominance and allele frequency interact to determine the rate of evolution • When a recessive allele is common (and a dominant allele is rare) evolution by natural selection is rapid • When the recessive allele is rare, and the dominant allele is common, evolution by natural selection is slow • A) The decline in frequency of a lethal recessive allele. As the allele becomes rare, the rate of evolution slows dramatically • B) The increase of the corresponding dominant allele. • Natural selection is most potent as a mechanisms when it is acting on common recessive alleles and rare dominant alleles • When a recessive allele is rare, most copies are hidden in heterozygotes and protected from selection Selection on Heterozygotes and Homozygotes Selection favouring Heterozygotes • Heterozygote superiority or overdominance: heterozygotes have higher fitness than either homozygote. At equilibrium, the selective advantage enjoyed by the lethal allele when it is in heterozygotes exactly balances the obvious disadvantage it suffers when it is in homozygotes. • Research on fruit flies shows that natural selection can act to maintain two alleles at a stable equilibrium. One way this can happen is when heterozygotes have superior fitness • In previous examples, selection has favoured one allele over the other • We would expect that the favoured allele will reach a frequency of 100% and the disfavoured allele would disappear • By keeping a population at an equilibrium in which both alleles are, heterozygote superiority can maintain genetic diversity indefinitely • Fig 6.18 o One allele is viable and the other allele is lethal
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
Red. Evolved toward an equilibrium in which both alleles are maintained. This is due to heterozygote superior fitness to either homozygote o Blue. Represents the hypothesis that the V allele will rise in frequency- rapidly at first, then more slowly Selection favouring Homozygotes • It is possible for heterozygotes to have inferior fitness • Underdominance: one kind of homozygote that has higher fitness than the other • P=0.25 pq=0 q=0.25 • One possible reason is heterozygotes are inviable • When heterozygotes have inferior fitness, one allele tends to go to fixation while the other allele is lost • However, different populations may lose different alleles • Heterozygote inferiority leads to loss of genetic diversity within populations • By driving alleles to fixation, heterozygote inferiority may help maintain genetic diversity among populations o
6.4| Mutation Adding Mutation to the HW Analysis: Mutation as an Evolutionary Mechanism • Second on the list of assumptions, no mutations • Back mutations that restore function are much less common than loss-of-function mutations • Mutation is a very weak mechanism of evolution, has virtually no effect • However, over very long periods of time, mutation can eventually produce appreciable changes in allele frequency • HW analysis shows that mutation is a weak mechanisms of evolution since it is a less efficient mechanism of allele frequency change Mutation and Selection • In combination with selection, mutation becomes a crucial piece of evolutionary process • Research with bacteria shows that while mutation itself is only a weak mechanism of evolution, it nonetheless supplies the raw material on which natural selection acts • Without mutation, evolution would eventually grind to a halt • Mutation is the ultimate source of genetic variation Mutation-Selection Balance • Most mutations are deleterious, and selection acts to eliminate such mutations from populations • At the same time selection removes deleterious alleles from a population, mutation constantly supplies new copies • In some cases, this balance between mutation and selection may explain the persistence of deleterious alleles in populations Are the alleles that cause Cystic Fibrosis maintained by a balance between Mutation and Selection? • In some cases, the frequency of a deleterious allele may be too high to explain by mutation-selection balance
BIOL 359 Evolution • •
Lecture 6 Population Genetics part I
Janice Wong
This may be a clue that heterozygotes have superior fitness Cystic fibrosis disease alleles are maintained in human populations because heterozygotes have superior fitness during typhoid fever epidemics
9.4| Modes of Selection and the Maintenance of Genetic Variation • •
Selection on a population may take any of a variety of forms Directional and stabilizing selection are common, disruptive selection is rare
Directional Selection • Fitness consistently increase (or decreases) with the value of a trait • Directional selection on a continuous trait can change the average value of the trait in the population • Reduces variation in a population Stabilizing Selection • Individual with intermediate values of a trait have highest fitness • Stabilizing selection on a continuous trait does not alter the average value of the trait in the pop. • Trims off the tails of the trait's distribution, thereby reducing variation Disruptive Selection • Individuals with extreme values of a trait have the highest fitness • Disruptive selection on a continuous trait does not alter the average value of the trait in the pop • Trims off the top of the traits distribution, thereby increasing the variance Example of stabilizing selection • A fly called Eurosta solidaginis injects an egg into a bud. After hatching the fly larva digs into the stem and induces the plant to form a protective gall. • May fall victim to two kinds of predators • Female Parastoid wasps kill fly larvae inside small galls at higher rate than they kill large inside large galls • A bird may spot the gall and break it open. Birds tend to favour smaller galls • Together, selection by wasps and selection by birds add up to stabilizing selection on gall size Example of disruptive selection • Studied an African finch called the black-bellied seedcracker • These birds exhibit two distinct beak sizes- large and small • The survivors were birds with bills that were either relative large or relative small • Birds with beaks of intermediate size did not survive to adulthood How is genetic variation for fitness maintained? 1. Most populations are not in evolutionary equilibrium with respect to directional and/or stabilizing selection. In any population, there is a steady slow supply of new favourable mutations creating genetic variation for fitness related traits
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
2. There is a balance between deleterious mutations and selection. There is a steady supply of new deleterious mutations. Selection will keep any given deleterious allele at low frequency, allowing substantial genetic variation to persist at the equilibrium between mutation and selection 3. Disruptive selection may be more common than is generally recognized. Other patterns that maintain genetic variation include frequency-dependent selection, in which rare phenotypes and genotypes have higher fitness than common ones.
Lecture 6 Population Genetics part I
Janice Wong
Chapter 6: Mendelian Genetics in Populations I- Selection and Mutation as Mechanisms of Evolution 5.4| Measuring Genetic Variation in Natural Populations How Much Genetic Diversity Exists in a Typical Population • Early efforts to study allelic diversity in populations were based on allozyme electrophoresis • Isolating proteins from a large sample of individuals, separating the proteins in an electrophoresis gel, and then staining the gel to visualize the proteins produced by a particular gene • If alleles in a population were different enough that their proteins products had different sizes or charges, then proteins would migrate differently in the gel and would show up as different bands • Demonstrated that most natural populations have substantial genetic varation • Not as accurate • Recent studies have shown that in most populations, many alleles are present at every gene in the genome. Genetic variation is extensive • Genetic diversity is maintained by natural variation
6.1| Mendelian Genetics in Populations: The Hardy-Weinberg Equilibrium Principle • •
Population genetics begins with a model of what happens to allele and genotype frequencies in an idealized population Once we know how Mendelian genes behave in the idealized population, we will be able to explore how they behave in real populations
A Stimulation • Gene pool: the set of all copies of all alleles in a population that could potentially be contributed by the members of one generation to the members of the next generation • Starting with the eggs and sperm that constitute the gene pool, our model traces alleles through zygotes and adults and into the next generation’s gene pool • When the alleles frequencies from the start are different from the end of the generation, then the population has evolved • Genetic Drift: change in frequencies of alleles in a population resulting from sampling error in drawing gametes from the gene pool to make zygotes and from chance variation in the survival and/or reproductive success of individuals; results in nonadaptative evolution A Numerical Calculation • Punnett squares can be used to predict genotypes of offspring by making crosses between two heterozygotes • Can also calculate genotype frequencies among the zygotes by multiplying allele frequencies
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
The Hardy Weinberg equilibrium principle yields two fundamental conclusions 1. The allele frequencies in a population will not change, generation after generation 2. If the allele frequencies in a population are given by p and q, then genotype frequencies will be given by p2, 2pq, q2 Hardy Weinberg Assumptions 1. There is no selection. • All members have survival at equal rates and contribute equal numbers of gametes to the gene pool (equal reproductive success) • When violated: the frequencies may change from one generation to the next 2. There is no mutations • No copies of existing alleles were converted by mutation, no new alleles created • When violated: some alleles with higher mutations rates, allele frequencies may change from one generation to the next 3. There is no migration • No individuals moved into or out of the model population' • When violated: individuals carrying some alleles move into or out of the population at higher rates than individual carrying other alleles, allele frequencies may change from on e generation to the next 4. There are no chance events • No genetic drift, and the model population is indefinitely large • When violated: if some individuals contribute more alleles to the next generation than others, allele frequencies may change from one generation to the next 5. Mating is random • When violated: genotype frequencies may change. Shifts in genotype frequency and in combination of the other 4 assumptions, can influence the evolution of populations
6.2| Selection • • •
Selection happens when individuals with particular phenotypes survive to reproductive age at higher rates than other phenotypes Or when individuals with particular phenotypes produce more offspring during reproduction than individuals with other phenotypes Selection can lead to evolution when phenotypes that exhibit difference in reproductive success are heritable
Adding Selection to the Hardy-Weinberg Analysis: Changes in Allele Frequencies • Selection can cause allele frequencies to change across generations • Violation of the no-selection assumption has resulted in violation of conclusion 1 of the Hardy-Weingberg analysis • The numerical examples shows that when individuals with some genotypes survive at higher rates than individuals with other genotypes, allele frequencies can change from one generation to the next • Natural selection causes change in allele frequencies, causes evolution • Fig 6.12
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
Each curve shows the change in allele frequency over time under a particular selection intensity Adding Selection to the Hardy-Weinberg Analysis: The Calculation of Genotype Frequencies • Selection can change genotype frequencies so that they cannot be calculated by multiplying the allele frequencies • Natural selection can also drive genotype frequencies away from the values predicted under the Hardy-Weinberg equilibrium principle • In this experiment, there was a strong natural selection for homozygotes • Genotype frequencies have changed among the adult survivors • Violation of the no-selection assumption has resulted in violation of conclusion 2 • The discovery that genotype frequencies in a population are not in HW equilibrium may be a clue that natural selection is at work o
6.3| Patterns of Selection: Testing Predictions of Population Genetic Theory Selection on Recessive and Dominant Alleles • Fig 5.16 • The curves predict that evolution will be rapid at first but will slow as the experiment proceeds • Dominance and allele frequency interact to determine the rate of evolution • When a recessive allele is common (and a dominant allele is rare) evolution by natural selection is rapid • When the recessive allele is rare, and the dominant allele is common, evolution by natural selection is slow • A) The decline in frequency of a lethal recessive allele. As the allele becomes rare, the rate of evolution slows dramatically • B) The increase of the corresponding dominant allele. • Natural selection is most potent as a mechanisms when it is acting on common recessive alleles and rare dominant alleles • When a recessive allele is rare, most copies are hidden in heterozygotes and protected from selection Selection on Heterozygotes and Homozygotes Selection favouring Heterozygotes • Heterozygote superiority or overdominance: heterozygotes have higher fitness than either homozygote. At equilibrium, the selective advantage enjoyed by the lethal allele when it is in heterozygotes exactly balances the obvious disadvantage it suffers when it is in homozygotes. • Research on fruit flies shows that natural selection can act to maintain two alleles at a stable equilibrium. One way this can happen is when heterozygotes have superior fitness • In previous examples, selection has favoured one allele over the other • We would expect that the favoured allele will reach a frequency of 100% and the disfavoured allele would disappear • By keeping a population at an equilibrium in which both alleles are, heterozygote superiority can maintain genetic diversity indefinitely • Fig 6.18 o One allele is viable and the other allele is lethal
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
Red. Evolved toward an equilibrium in which both alleles are maintained. This is due to heterozygote superior fitness to either homozygote o Blue. Represents the hypothesis that the V allele will rise in frequency- rapidly at first, then more slowly Selection favouring Homozygotes • It is possible for heterozygotes to have inferior fitness • Underdominance: one kind of homozygote that has higher fitness than the other • P=0.25 pq=0 q=0.25 • One possible reason is heterozygotes are inviable • When heterozygotes have inferior fitness, one allele tends to go to fixation while the other allele is lost • However, different populations may lose different alleles • Heterozygote inferiority leads to loss of genetic diversity within populations • By driving alleles to fixation, heterozygote inferiority may help maintain genetic diversity among populations o
6.4| Mutation Adding Mutation to the HW Analysis: Mutation as an Evolutionary Mechanism • Second on the list of assumptions, no mutations • Back mutations that restore function are much less common than loss-of-function mutations • Mutation is a very weak mechanism of evolution, has virtually no effect • However, over very long periods of time, mutation can eventually produce appreciable changes in allele frequency • HW analysis shows that mutation is a weak mechanisms of evolution since it is a less efficient mechanism of allele frequency change Mutation and Selection • In combination with selection, mutation becomes a crucial piece of evolutionary process • Research with bacteria shows that while mutation itself is only a weak mechanism of evolution, it nonetheless supplies the raw material on which natural selection acts • Without mutation, evolution would eventually grind to a halt • Mutation is the ultimate source of genetic variation Mutation-Selection Balance • Most mutations are deleterious, and selection acts to eliminate such mutations from populations • At the same time selection removes deleterious alleles from a population, mutation constantly supplies new copies • In some cases, this balance between mutation and selection may explain the persistence of deleterious alleles in populations Are the alleles that cause Cystic Fibrosis maintained by a balance between Mutation and Selection? • In some cases, the frequency of a deleterious allele may be too high to explain by mutation-selection balance
BIOL 359 Evolution • •
Lecture 6 Population Genetics part I
Janice Wong
This may be a clue that heterozygotes have superior fitness Cystic fibrosis disease alleles are maintained in human populations because heterozygotes have superior fitness during typhoid fever epidemics
9.4| Modes of Selection and the Maintenance of Genetic Variation • •
Selection on a population may take any of a variety of forms Directional and stabilizing selection are common, disruptive selection is rare
Directional Selection • Fitness consistently increase (or decreases) with the value of a trait • Directional selection on a continuous trait can change the average value of the trait in the population • Reduces variation in a population Stabilizing Selection • Individual with intermediate values of a trait have highest fitness • Stabilizing selection on a continuous trait does not alter the average value of the trait in the pop. • Trims off the tails of the trait's distribution, thereby reducing variation Disruptive Selection • Individuals with extreme values of a trait have the highest fitness • Disruptive selection on a continuous trait does not alter the average value of the trait in the pop • Trims off the top of the traits distribution, thereby increasing the variance Example of stabilizing selection • A fly called Eurosta solidaginis injects an egg into a bud. After hatching the fly larva digs into the stem and induces the plant to form a protective gall. • May fall victim to two kinds of predators • Female Parastoid wasps kill fly larvae inside small galls at higher rate than they kill large inside large galls • A bird may spot the gall and break it open. Birds tend to favour smaller galls • Together, selection by wasps and selection by birds add up to stabilizing selection on gall size Example of disruptive selection • Studied an African finch called the black-bellied seedcracker • These birds exhibit two distinct beak sizes- large and small • The survivors were birds with bills that were either relative large or relative small • Birds with beaks of intermediate size did not survive to adulthood How is genetic variation for fitness maintained? 1. Most populations are not in evolutionary equilibrium with respect to directional and/or stabilizing selection. In any population, there is a steady slow supply of new favourable mutations creating genetic variation for fitness related traits
BIOL 359 Evolution
Lecture 6 Population Genetics part I
Janice Wong
2. There is a balance between deleterious mutations and selection. There is a steady supply of new deleterious mutations. Selection will keep any given deleterious allele at low frequency, allowing substantial genetic variation to persist at the equilibrium between mutation and selection 3. Disruptive selection may be more common than is generally recognized. Other patterns that maintain genetic variation include frequency-dependent selection, in which rare phenotypes and genotypes have higher fitness than common ones.
