Name __________________________________________
Date ___________
Period ________
AP Biology
Using Computer Simulations to Explore Population Genetics
Learning Objectives
 Use a data set that reflects a change in the genetic makeup of a population over time and to apply mathematical
methods and conceptual understandings to investigate the cause(s) and effect(s) of this change
 Apply mathematical methods to data from a simulated population to predict what will happen to the population
in the future
 Evaluate evidence that describes evolutionary changes in the genetic makeup of a population over time
 Evaluate data sets that illustrate evolution as an ongoing process
Background
In 1908, G.H. Hardy and W. Weinburg independently suggested a mathematical approach to study evolution. In this
approach, evolution is viewed as changes in the frequency of alleles in a population of organisms. The Hardy-Weinburg
theorem can be sued to predict the frequencies that one would expect of different genotypes in a population. Of what
value is such a prediction? It provides a meter stick by which changes in a population – changes in allele frequency, and
thereby evolution – can be measured. If there is a change, then one can further investigate: “What force(s) (change) is
acting on this population to cause this change over time?”
Pre-lab Questions
1. What is the Hardy-Weinberg theorem?
2.
What does each of the variables represent?
3.
What conditions are necessary for a population to be in Hardy-Weinberg equilibrium?
Introduction
The purpose of this activity is to help you explore how selection and mutation cause evolution. You will use a
web-based simulation of an evolving population to test your hypotheses, and to answer a variety questions concerning
changes in the frequencies of alleles. To access the simulation, go to:
http://www.radford.edu/~rsheehy/Gen_flash/popgen/. You may need to update your version of FlashPlayer to make it
run.
This application simulates evolution at a single locus in an ideal population. The locus has 2 alleles: A1 and A2.
The user can change the initial frequency of A1. The application also allows the user to enter parameters controlling
selection (fitness), mutation, migration, drift, and inbreeding (bottleneck). The application then plots a graph showing the
frequency of allele A1 over time. Each generation's frequency is calculated from the previous generation's frequency,
according to the Hardy-Weinberg Equilibrium.
This simulator is easy to use. Small boxes in at the top of the screen (Figure 1) allow you to enter and change the
parameters for the simulation. There are buttons that allow you to run the simulation, clear the graph, reset all parameters
to their default values, and ask questions. To print your graphs, create a screenshot, and save the file to your computer.
Take a few moments to fiddle with the settings of the application. If you have questions about any of the bits and pieces,
click on the “?”.
Figure 1: Screenshot of Population Genetics Simulator Application
Simulations
Case 1: Hardy-Weinberg Equilibrium
After fiddling with the simulation program to see how it works, restore all parameters to their default settings. Click
“Finite Population” in the top left corner. The default settings encompass initial frequencies of 0.5 for both alleles, and the
assumptions of no selection, no mutation, no migration, no genetic drift, and random mating. Run the simulation to verify
that under these conditions the allele frequencies do not change. Try different values for the starting frequency of allele
A1.
4. Does your experimentation verify that any starting frequencies are in equilibrium so long as there is no selection,
no mutation, no migration, and no drift?
5.
What does this mean about the population?
Case 2: Selection Against Homozygous recessive
There are three boxes that let you set the fitness for the three genotypes. The fitness allows you to play with the effects of
selection (that is, differences between the genotypes in survival or reproduction). Setting the values to 1, 0.8, and 0.2, for
example, is equivalent to specifying that for every 100 individuals of genotype A1A1 that survive to reproduce, 80
individuals of genotype A1A2 survive, and 20 individuals of genotype A2A2 survive.
6. Predict what will happen if you set the fitness of A1A1, A1A2, and A2A2 to 1, 1, and 0.0, respectively. Start with
population size of 100, go for 10 generations. Then run the simulation. Sketch your results in the spaces below.
Was your prediction correct? Explain.
Prediction:
Result:
Explanation:
7.
How do the new p and q frequencies compare to the starting (parental) frequencies?
8.
Since the homozygous recessives are strongly selected against, would you expect the recessive (A2) allele to be
completely removed from the population? In other words, in a large population would it be possible to
completely eliminate a deleterious (or even lethal) recessive allele? Explain.
9.
Now set the initial frequency of allele A1 to 0.01, and the fitness to 1, 1, and 0.99. What happens when you run the
simulation? Why? Now try fitness of 1, 1, and 0.95. Sketch your results in the spaces below. Can you explain the
difference?
Fitness of 1, 1, and 0.99
Fitness of 1, 1, and 0.95:
Explanation:
Case 3: Heterozygote Advantage
From Case 2, it is easy to see what happens to the lethal recessive allele in a population. However, data from human
populations sometimes show an unexpected high frequency of a deleterious allele in some populations. Sometime there
is a slight advantage to being heterozygous for a trait rather than homozygous dominant. So the situation is now more
complicated; homozygous recessives are still strongly selected against and do not survive to reproduce, but additionally,
homozygous dominants have a lower reproductive rate than heterozygotes. We will incorporate this information into the
simulation.
10. Predict what will happen if you set the fitness of A1A1, A1A2, and A2A2 to .5, 1, and 0 respectively. Start with
population size of 100, go for 100 generations. Then run the simulation. Sketch your results in the spaces below.
Was your prediction correct? Explain.
Prediction:
Result:
Explanation:
11. Explain how the changes in p and q frequencies in case 3 compare with the frequencies in Case 1 (H-W
equilibrium) and Case 2(selection)?
12. Do you think the recessive allele will be eliminated from the population in case 3? (Hint: Hit “continue” a few
times on the simulator and see where the lines go.)
13. What is the impact of heterozygote advantage to genetic variation in a population?
14. Give a real-life example of heterozygote advantage?
Case 4: Genetic Drift
Remember that even though natural selection is creating adaptive change, it is not the only force molding a population.
Equally important are the forces of random chance that can cause changes over time in a population even though they are
not adaptive. We will simulate this using the “Bottleneck” button on the simulator.
15. Imagine a population of shipwrecked colonists. The original population had equal p and q frequencies. After a
few generations, disease and famine decimated most of the population. Predict what will happen if you set the
fitness of A1A1, A1A2, and A2A2 to 1, 1, and 1 respectively. Start with population size of 100, go for 100
generations. Set the bottleneck to start at generation 10 and end at generation 20, with a bottleneck population
(BN) of 30 (only 30 colonists survived to reproduce). Then run the simulation. Sketch your results in the spaces
below. Was your prediction correct? Explain.
Prediction:
Result:
Explanation:
16. Give a Real-life example of a bottleneck.
17. Compare the initial allele frequencies with the final allele frequencies.
18. What do these results indicate about the importance of population size as an evolutionary force?
19. How is this issue significant in conservation biology and endangered species conservation?
Mutation as a mechanism of evolution
20. There are 2 boxes in the simulator’s window that let you play with the mutation rate. One controls the rate at
which copies of A1 turn into A2’s; a mutation rate of 0.001 means that each generation one out of every thousand
A1’s turns into an A2. The other box controls the mutation rate in the other direction. Note that the mutation rate
should be a number between 0 and 1 (why?). If you enter a number outside this range you will get weird
behavior. Return all parameters to their default values, then set the mutation rates to 0.0001 and 0. Were you
correct? For any real gene a mutation rate of 0.0001 would be extraordinarily high. How effective is mutation, by
itself, as a force of evolution?
Prediction:
Explanation:
Result:
Mutation-Selection Balance
Consider the case of cystic fibrosis. Cystic fibrosis is a recessive genetic disease caused by loss-of-function mutations in
the CFTR gene. Affected individuals suffer chronic respiratory infections that ultimately cause severe lung damage. Let
A2 be the normal allele (C) and A1 the mutant allele (c).
21. Until recently, very few cc individuals survived long enough to reproduce. Return all parameters to their default
values, then set the fitness to 0, 1, and 1. What is the frequency of the c allele after 500 generations? Why?
22. The actual frequency of the c allele is about 0.02 in European populations. One hypothesis for the maintenance of
this frequency is that new copies of the c allele are continuously created by mutation. With fitness of 0, 1, and 1,
how high does the mutation rate from A2 to A1 need to be to achieve an equilibrium frequency of 0.02 for allele
A1?
23. The actual rate of mutations creating new c alleles is about 0.00000067. Is a balance between mutation and
selection a plausible explanation the maintenance of the c allele at a frequency of 0.02? If not, develop an
alternative explanation and use AlleleA1 to demonstrate that it is plausible.
Problem Set
24. In fruit flies, Drosophila melanogaster, the allele for normal-length wing is dominant over the allele for vestigial
wings (vestigial wings are stubby little curls that cannot be used for flight). In a population of 1,000 individuals,
360 show the recessive phenotype. How many individuals would you expect to be homozygous dominant and
how many would be heterozygous for this trait?
25. The allele for unattached ear lobes is dominant over the allele for attached earlobes. In a population of 500
individuals, 25% show the recessive phenotype. How many individuals would you expect to be homozygous
dominant and how many would be heterozygous for this trait?
26. The allele for the hair pattern called “widow’s peak” is dominant over the allele for no “widow’s peak”. In a
population of 1,000 individuals, 510 show the dominant phenotype. How many individuals would you expect of
each of the three possible genotypes for this trait?
27. In certain African countries, 4% of the newborn babies have sickle-cell anemia, which is a recessive trait. Out of a
random population of 1,000 newborn babies, how many would you expect of the three possible genotypes for this
trait?
Literature Cited
Goddard, H. H. 1914. Feeble-mindedness: Its causes and consequences. The Macmillan Company, New York.
Mukai, T., and A. B. Burdick. 1959. Single gene heterosis associated with a second chromosome recessive lethal in
Drosophila melanogaster. Genetics 44: 211-232.
Wallace, B. 1963. The elimination of an autosomal lethal from an experimental population of Drosophila melanogaster.
American Naturalist 97: 65-66.
Wirth, B., T. Schmidt, et al. 1997. De novo rearrangements found in 2% of index patients with spinal muscular atrophy:
Mutational mechanisms, parental origin, mutation rate, and implications for genetic counseling. American Journal of
Human Genetics 61: 1102-1111.
Modified from Selection and Mutation as Mechanisms of Evolution by Jon C. Herron, University of Washington and
Population Genetics by Kim Foglia, 2008.