Population Genetics Notes

POPULATION GENETICS

• Micro-evolutionary change in populations.

GENETIC VARIATION IN POPULATIONS

• Mutation is the ultimate source of genetic variation.
• Mutation alone cannot account for differences in genetic disease incidence among ethnic groups (Jorde, Carey, and Bamshad, 2010).
• Example: Sickle cell anemia is more common in people of African descent compared to Northern Europeans.

BASIC CONCEPTS OF PROBABILITY

• Probability is important for explaining and analyzing genetic variation in populations.
• Probability is defined as the proportion of times a specific outcome occurs in a series of events.
• Probabilities range between 0 and 1, inclusive.
• If an event is certain, probability = 1.
• If an event is impossible, probability = 0.

PROBABILITY IN GAMETE FORMATION

• Normal meiosis results in transmission of one copy of each chromosome pair to each egg or sperm cell.
• Alleles on chromosomes are transmitted similarly.
• Probability of transmitting a given member of a pair is $1/2$ (0.5).
• The probabilities of all events in a given situation must add up to 1.

MULTIPLICATION RULE

• If two trials are independent, the probability of obtaining a given outcome in both trials is the product of the probabilities of each outcome.
• The probability of a parent transmitting one of two alleles at a locus is independent from one reproductive event to the next.

ADDITION RULE

• To find the probability of either one outcome or another, add the respective probabilities together.

UNDERSTANDING TERMS

• Populations: Local groups of organisms belonging to the same species.
• A population consists of all individuals of the same species that live in the same place at the same time.
• Gene pool: The set of genetic information carried by the members of a sexually reproducing population.
• Allele frequency: The frequency with which alleles of a given gene are present in a population.

TERMS CONTINUED

• Hardy-Weinberg Law: Allele and genotype frequencies remain constant from generation to generation when the population meets certain assumptions.
• Genetic drift: Random fluctuations of allele frequencies from generation to generation in small populations.
• Founder effects: Allele frequencies established by chance in a population started by a small number of individuals.

TERMS CONTINUED

• Fitness: Measure of the relative survival and reproductive success of a given individual or genotype in a particular environment.
• Natural selection: Differential reproduction shown by some members of a population that is the result of differences in fitness.

Genetic Variation in Populations

• Genetic variation can be measured by observing the number, frequency, and kinds of alleles in a population.
• An allele is one of two or more alternate forms of a gene.

POPULATION GENETICS

• Study of genetic variability within a population and the forces that act on it.
• At genetic equilibrium, a population is not evolving.

GENE POOL

• Each population has a gene pool, which includes all alleles for all loci present in the population.
• Each individual has a different subset of alleles in the gene pool.

FREQUENCIES

• Frequencies of genotypes, phenotypes, and alleles are expressed as decimal fractions.
• Genotype frequency: Proportion of a particular genotype in a population. The sum of all genotype frequencies is one (1).
• Phenotype frequency: Proportion of a particular phenotype in a population.
• If each genotype corresponds to a specific phenotype, then the genotype and phenotype frequencies are the same.

GENOTYPE AND PHENOTYPE FREQUENCIES

• Hypothetical population of 1000 individuals (complete dominance):
  • Genotype frequencies:
    • TT: 460 (0.46)
    • Tt: 430 (0.43)
    • tt: 110 (0.11)
  • Phenotype frequencies:
    • Dominant: 890 (0.89)
    • Recessive: 110 (0.11)

ALLELE FREQUENCIES

• Allele frequency: Proportion of a specific allele in a particular population.
• In a population of 1000 diploid individuals, there are 2000 alleles.
• Example:
  • Allele A: 1200 (0.6)
  • Allele a: 800 (0.4)

THE HARDY – WEINBERG PRINCIPLE

• Mathematical prediction that allele frequencies do not change from generation to generation in a large population in the absence of microevolutionary forces.
• If $(p)$ represents the frequency of the dominant allele $(A)$ and $(q)$ the frequency of the recessive allele $(a)$, their relationship can be summarized with a simple binomial equation:
• $p + q = 1$ (allele frequencies)
• Genotype frequencies can be estimated using the equation: $(p^2 + 2pq + q^2 = 1)$

GENETIC EQUILIBRIUM

• Hardy-Weinberg principle tells us what to expect when a sexually reproducing population is not evolving.
• Relative proportions of alleles and genotypes in successive generations will remain the same provided that 5 conditions are met.

GENETIC EQUILIBRIUM CONDITIONS

• 1. Random mating
• 2. No net mutations
• 3. Large population size
• 4. No migration
• 5. No natural selection

FACTORS RESPONSIBLE FOR EVOLUTIONARY CHANGE

• There are five factors responsible for evolutionary change.
• 1. Nonrandom mating
• 2. Mutation
• 3. Genetic drift
• 4. Gene flow
• 5. Natural selection

EVOLUTION- DEPARTURE FROM GENETIC EQUILIBRIUM

• Microevolution: Small-scale evolutionary change caused by changes in allele or genotype frequencies within a population over a few generations.
• Macroevolution: Large-scale evolutionary events over long time spans. Results in phenotypic changes significant enough to warrant placement in taxonomic groups at the species level and higher.
• The focus of population genetics is microevolution.

EVOLUTION AND NATURAL SELECTION

• Natural selection results from differential survival and reproduction, but individuals do not evolve during their lifetimes.
• Evolutionary change, including modifications in structure, physiology, ecology, and behavior, is inherited from one generation to the next.

EVOLUTION/ MICROEVOLUTION

• Evolution: Accumulation of inherited changes within populations over time.
• Biological evolution occurs in populations, not individuals.
• Microevolution: Change in allele or genotype frequencies within a population over successive generations (minor changes).

MACROEVOLUTION

• Large-scale phenotypic changes in populations that warrant placement in taxonomic groups at the species level and higher.
• Major evolutionary events usually viewed over very long time periods, such as formation of different species from common ancestors, using evidence from DNA analysis of fossils, etc.

AN EARLY THEORY OF BIOLOGICAL EVOLUTION

• Jean Baptiste de Lamarck was the first scientist to propose that organisms undergo change over time as a result of some natural phenomenon rather than divine intervention.
• Lamarck thought that organisms were endowed with a natural force that drove them towards greater complexity over time.
• He thought organisms could pass traits acquired in their lifetimes to their offspring.
• This is a transformational theory of evolution and not generally accepted by the scientific community today.

DARWIN AND EVOLUTION BY NATURAL SELECTION

• Darwin proposed a variational theory of evolution.
• He made 3 inferences from 5 observations for this theory.
• Observations 1, 2 & 3:
  • 1. All species have enormous reproductive potential.
  • 2. Yet their numbers remain constant.
  • 3. Natural resources are limited.
• Inference 1:
  • There is a struggle for existence which leads to competition for resources.

DARWIN’S THEORY CONTINUED

• Observations 4 & 5:
  • 4. Variation exists between organisms of a species.
  • 5. Variation (genetic) is heritable.
• Inferences 2 & 3:
  • 2. Variations which favor survival confer selective advantage.
  • 3. Environmental factors which become limiting, exert selection pressure on a population.

MICROEVOLUTIONARY PROCESSES

• 1. Nonrandom mating
• 2. Mutation
• 3. Genetic drift
• 4. Gene flow
• 5. Natural selection

NONRANDOM MATING CHANGES GENOTYPE FREQUENCIES

• 1. Inbreeding:
  • Inbreeding depression: Inbred individuals have lower fitness than those not inbred (less chance of successful reproduction).
  • Fitness: Relative ability of a given genotype to make a genetic contribution to subsequent generations.
• 2. Assortative mating: Individuals select mates by their phenotypes.

ASSORTATIVE MATING

• Like inbreeding, assortative mating usually increases homozygosity at the expense of heterozygosity but does not change the overall allele frequencies in the population.
• However, assortative mating changes genotype frequencies only at the loci involved in mate choice, whereas inbreeding affects genotype frequencies in the entire genome.

MUTATION AND EVOLUTION

• Variation is introduced into a population through mutation.
• Mutations do not determine the direction of evolutionary change.
• Mutation by itself causes only small deviations in allele frequencies from those predicted by the Hardy-Weinberg principle.

MUTATION – SELECTION BALANCE

• The balance that occurs where new mutations introduce harmful alleles, whereas natural selection removes them.
• This process predicts that gene frequencies should be lower for diseases caused by dominant alleles, in which most alleles are exposed to natural selection, than in recessive diseases, where most alleles are found in heterozygotes in a population and are thus protected from natural selection.

GENETIC DRIFT

• Shift in allele and genotype frequencies away from the frequencies observed in previous generations.
• Genetic drift results from random evolutionary changes in small breeding populations.
• Causes of genetic drift include the founder effect and population bottlenecks.

GENETIC DRIFT

• Random events, or chance, tend to cause changes (in allele frequencies) of relatively greater magnitude in small populations.
• An allele may be eliminated from the population purely by chance, regardless of whether it is beneficial, harmful, or of no significance.

POPULATION BOTTLENECKS

• Occur when a population goes through a rapid and marked decrease in numbers.
• Genetic drift can occur in the small population of survivors.
• Example: Cheetah population reduced suddenly at the end of the last ice age 10,000 years ago.

BOTTLENECKS CONTINUED

• Reduction in the population reduces the gene pool; therefore, the variety of alleles that natural factors can select from are reduced.
• It also increases the chance that harmful recessive alleles may be inherited from both parents.

BOTTLENECKS

• Genetic Drift-Bottleneck Effect Example Diagram is shown which includes: Parent population, Bottleneck (drastic reduction in population), Surviving individuals, and the Next generation.

THE FOUNDER EFFECT

• The type of genetic drift that occurs when a small number of individuals from a large population establish (found) a new colony is called the founder effect.
• Traits carried by one or a small number of early settlers often end up in a large fraction of their descendants.

GENETIC DRIFT & FOUNDER EFFECT

• An example of how allele frequencies can change with the founder effect is given: Initial frequencies may be $AA = 0.36$, $Aa = 0.48$, and $aa = 0.16$. After the founder effect, the frequencies might shift to $AA = 0.48$, $Aa = 0.43$, and $aa = 0.09$

FOUNDER EFFECT- HUMAN EXAMPLE 1

• The descendants of Corporal William Glass living on the Isle of Tristan da Cunha form a population that exhibits the founder effect.
• In this population, a deformity of the fifth finger, clinodactyly, is present at a higher than average frequency.
• Clinodactyly is an inherited trait passed on from Corporal Glass to his descendants.

FOUNDER EFFECT

• A few individuals from a population start a new population with a different allele frequency than the original population.
• Image of individuals moving from a mainland to populate an island.

HUMAN EXAMPLE 2 OF THE FOUNDER EFFECT

• Ellis-van-Creveld syndrome, a rare disorder that involves reduced stature, polydactyly, and congenital heart defects, is seen with greatly elevated frequency among the old order Amish population of Pennsylvania.
  • The Amish population was founded in the United States by about 50 couples. This small population size increased the potential for genetic drift, resulting in increased frequencies of certain disease-causing alleles.

GENE FLOW

• The migration of breeding individuals between populations causes a corresponding movement of alleles or gene flow, which has significant evolutionary consequences.
• Gene flow has occurred between most human populations.
• Very few isolated human populations are now left on the planet.
• Gene flow increases genetic variability within the recipient populations but decreases variability between the populations involved.

NATURAL SELECTION

• Differential reproduction of individuals within a population in response to environmental factors. Limiting factors may exert selection pressure.
• Variation in phenotypic expression exists among individuals in a population. Some phenotypes have a selective advantage in a particular environment. Individuals with the selective advantage survive to reproduce and pass on their advantageous traits to the next generation.
• Natural selection changes allele frequencies in a way that increases adaptation.
• Natural selection operates on an organism’s phenotype.

NATURAL SELECTION

• Mutation creates variation. Unfavorable mutations are selected against. Reproduction and mutation occur and favorable mutations are more likely to survive and reproduce.

POLYGENIC INHERITANCE AND NORMAL DISTRIBUTION

• When characters are under polygenic control, a range of phenotypes occurs, with most members of the population located in the median range and fewer at the extremities.
• This forms a normal distribution or standard bell curve.
• Deviations from this normal distribution can be observed when different selection pressures act on populations.

POLYGENIC INHERITANCE

• Illustration shown demonstrating skin pigmentation variance following a normal distribution.

NORMAL DISTRIBUTION CURVE

• Standard bell curve graph is shown.

MODES OF SELECTION

• Stabilizing selection.
• Directional selection.
• Disruptive selection

MODES OF SELECTION

• Illustrations demonstrating the effects of disruptive selection, stabilizing selection, and directional selection before and after selection.

MODES OF SELECTION

• Directional Natural Selection: Snuzzle coloration best adapted to conditions changes the average coloration in the population.
• Stabilizing Natural Selection: Light and dark snuzzles are eliminated maintaining the same average but increasing the number of individuals with intermediate coloration.
• Diversifying Natural Selection: Intermediate-colored snuzzles are selected against increasing the number of snuzzles with light and dark coloration.

MODES OF SELECTION CONTINUED

• Graphs illustrating directional, stabilizing, and disruptive selection on a normal distribution.

BALANCED POLYMORPHISM

• A special type of genetic polymorphism in which two or more alleles for a trait persist in a population over many generations as a result of natural selection.
• Genetic variation may be maintained by heterozygote advantage.
• Demonstrated in humans by the selective advantage of heterozygous carriers of the sickle cell allele.

POLYMORPHISM

• Polymorphism describes the existence of different forms in a population.

HETEROZYGOTE ADVANTAGE- EXAMPLE SICKLE CELL ANEMIA

• Heterozygote advantage in sickle cell anemia described.

THE SICKLE CELL ALLELE

• The allele that causes sickle cell is very harmful, but recessive to the normal hemoglobin allele.
• Selection pressure would be expected to remove this allele from the population.
• The allele persists due to heterozygote advantage.
• Heterozygotes have a survival advantage in regions of the world where Falciparum malaria is prevalent.

SICKLE CELL ALLELE

• (a) GENOTYPES PHENOTYPES SURVIVAL IN MALARIAL REGIONS
• AA Normal for trait Low (death from malaria)
• Aa Sickle cell trait High ( survives both malaria and sickle cell anemia
• aa Sickle cell anemic very low (death from sickle cell anemia before reproductive age)

POPULATION GENETICS PROBLEM SOLVING

• USING THE HARDY WEINBERG PRINCIPLE TO CALCULATE GENOTYPE AND PHENOTYPE FREQUENCIES
• If complete dominance governs the inheritance of a trait, always begin Hardy-Weinberg calculations by determining the frequency of the homozygous recessive genotype.
• Pay attention to the type of frequency that the question is asking you to calculate. i.e. allele or genotype frequency.

POPULATION GENETICS PROBLEM SOLVING CONTINUED

• Co-dominant or incompletely dominant allele frequencies can be measured directly.
• Genotype MM MN NN Total
• Number of individuals 54 26 20 100
• Number of LM alleles 108 26 0 134
• Number of LN alleles 0 26 40 66
• Total 108 52 40 200
• Frequency of LM in population: 134/ 200 = 0.67 = 67%
• Frequency of LN in population: 66/ 200 = 0.33 = 33%

PROBLEM SOLVING CONTINUED

• To calculate the genotype frequency use the equation : $p^2+2pq+q^2 = 1$
• To calculate the allele frequency use the equation : $p+q = 1$
• Traits which are inherited in a co- dominant or incompletely dominant fashion allow all three possible genotype frequencies to be observed directly and compared with calculated frequencies.

POPULATION GENETICS QUESTIONS

• Question 1.
• A breeding population of fruit flies is kept at a laboratory. The frequency of the allele for long wings (L) in this population is 0.8 and the frequency for short wings (l) is 0. 2
• What are the expected proportions of the genotypes LL, Ll and ll? Assume Hardy-Weinberg equilibrium.
• (3 marks)

QUESTION 2

• In snapdragons, flower color inheritance shows incomplete dominance. Red flowers are RR, pink are RW and white are WW.
• A. In a study of 747 snapdragon flowers, 233 were red, 385 were pink and 129 were white.
• What are the frequencies of alleles R and W? (4 marks)
• B. In a sample of 1279 snapdragon flowers, 363 were red, 634 were pink and 282 were white.
• Is this population in Hardy-Weinberg equilibrium? Explain your answer. (5 marks)

QUESTION 3

• A characteristic in one population is determined by an autosomal recessive allele (d). The individuals with the recessive genotype (dd) occur at a frequency of 0.25 in this population.
• What are the frequencies of allele (D) and (d)? Assume Hardy- Weinberg equilibrium. (3 marks)

QUESTION 4

• The frequency of sickle cell anemia in Haiti is about 1 in 10,000 births.
• (a) What is the expected frequency of the sickle cell trait (heterozygotes) in this population if no micro- evolutionary forces are acting on it?
• (b) In a population of 1 million, how many persons would be heterozygote carriers?
• Show all steps of your working and express your answer as a decimal fraction. (6 marks)

QUESTION 5

• The peppered moth, Biston betularia, produces a black variety from time to time. The mutation causing this black variety results in a dominant allele, B. The black variety was first observed in 1848 in Manchester, but by 1895 it had increased to 95% of the population in the city
• a. What was the frequency of the dominant allele, B, in the 1895 population of the moth? Show your calculations. (3)
• b. Explain why there are always some light- colored forms of the moth present in urban populations after 1895? (2)
• c. Explain why, in rural populations, the black form of the moth remains very rare. (2)
• CCEA

QUESTION 6

• Bacterial populations that have been exposed to an antibiotic develop resistance to it over time.
• a) Explain the genetic basis of resistance. (4 marks)
• b) Is bacterial antibiotic resistance an example of stabilizing selection, directional selection or disruptive selection? Explain. (3 marks)

QUESTION 7

• Many phenotypic characters that are under polygenic control show a normal distribution of phenotypes. Illustrate how each of the three types of natural selection can change the distribution of phenotypes from the normal distribution pattern by doing the following:
• - Draw and annotate three (3) graphs, one to represent each of the following types of natural selection: stabilizing; directional; disruptive. (10 marks)
• Show the normal distribution curve on each of the graphs using one color.
• Use different colors to show how the distribution differs from the normal pattern for each type of selection.

QUESTION 8

• Explain the effect on genetic variation (within or between species populations) of each of the processes listed below. (10 marks)
• Explain whether the process decreases, increases, or has no effect on the genetic variation. How does the process affect Hardy-Weinberg equilibrium in the population?)
• - natural selection
• - mutation
• - non – random mating
• - gene flow
• - genetic drift