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Lab 02 – Selection and mutation Introduction Mathematical models and computer simulations are important tools in biology. Such approaches range from simple (like the ones you will be using to explore evolution, here) to complex. Here, we would like you to use computer simulations how mutation, migration and selection affect allele frequencies, and hence the evolution of a population. Please download Allele A1 from this site: http://faculty.washington.edu/herronjc/SoftwareFolder/AlleleA1.html AlleleA1 allows you to view the allele and genotype frequencies at the end of a simulation. It also models one population at a time - if you need to see the results of several simulations, you will need to press “run” several times, use “auto” graph lines and “reset” or “clear” to return to starting conditions. Using tab will move you between the input boxes. You can change the y axis to show alleles and genotype frequencies. You can also change the scale on the x axis. Use the program to answer the questions below. In Windows, you can use a few tricks to copy the image from your simulations to a document file: 1. Click on the active window 2. Press ALT + PrtScrn (alt printscreen) 3. Place cursor in document 4. press CTRL + V. This is the approach used to copy the images above. (I don’t have an apple mac, but here are online instructions you can try http://still-scripts.com/mac-os-x/how-to-create-or-take-a-screen-shot-or-screen-caputrewith-your-apple-computer/) Questions 1. Hardy-Weinberg Equilibrium 1. After investigating the simulation program to see how it works, enter the default settings given in the image to the right. 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. 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? (2pts) Yes – an allele is maintained at a constant frequency when no evolutionary force acts on it. 2. Relative fitness There are three boxes that let you set the fitness values for the three genotypes. The fitness values allow 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. a. Predict what will happen if you set the fitness values of A1A1, A1A2, and A2A2 to 1, 0.8, and 0.2, respectively. Then run the simulation with several runs. Was your prediction correct? Please explain. (2pts) I personally was surprised at how fast selection acts. The population is at maximum genetic diversity at an allele frequency of 0.5. Therefore, all genotypes are present and there is a high opportunity for selection b. Now set the initial frequency of allele A1 to 0.01, and the fitness values to 1, 1, and 0.99. What happens when you run the simulation? Why? Now try fitness values of 1, 1, and 0.95. Can you explain the difference? (3pts) Despite a relatively small difference in fitness, the second scenario (green: 1,1,0) increases faster. This is because the frequency of heterozygotes increases faster in the population. Since both heterozygotes and A1A1 homozygotes are favored, there is more opportunity for selection. 3. Selection on recessive and dominant alleles. Restore all parameters to their default values, then set the initial frequency of allele A1 to 0.01. a. Predict what will happen when you try fitness values of 1, 1, and 0.9, then check your prediction. Now predict what will happen when you try fitness values of 1, 0.9 and 0.9, and check your prediction. Were your predictions correct? Please fully explain the results (you can run the two different scenarios on the graphs). (4pts) blue = 1, 1, 0.9, purple = 1.0, 0.9, 0.9 In the purple scenario, both A1A2 and A2A2 are equally unfit. A1 can only form heterozygotes when it is at low frequency. Therefore, there is little opportunity for selection. In contrast in the blue scenario both A1A1 and A1A2 are equally fit. As soon as A1A2 appear, they are selected for, increase in frequency, and then more homozygotes appear. b. In Question 3a, when was allele A1 dominant (with respect to fitness) and when was it recessive? (2pts) In scenario 1, A1 was dominant In scenario 2, A1 was recessive, because the heterozygote had the same phenotype as the homozygote A2A2 c. Which of the following will increase in frequency more rapidly when favored by selection: a rare recessive allele, or a rare dominant allele? Why? (Try running various combinations of initial frequencies and fitness values in AlleleA1) (2pts) A rare dominant allele. As soon as it starts forming heterozygotes, it will be favored by selection. d. Which rises to a frequency of 1.0 more rapidly under selection: a common recessive allele, or a common dominant allele? Why? (3pts) green = dominant, blue = recessive A common recessive allele. If A1 is dominant, it will always dominate A2. Therefore, at high frequencies of A1, A2 will always appear as a heterozygote – and “hide out” in this form. It is difficult to remove it from the population. Question 4. Selection in captive populations. Pacific oysters are introduced from Japan into the Pacific Northwest, where they are extensively cultured in aquaculture. Figure 1. Pacific oyster families were raised in a hatchery, allowed to settle on cultch and then outplanted in the marine environment. After a year, the offspring were sampled and genotyped. The results report the relative proportions of offspring genotypes at a locus scored in individual Pacific oyster families (112), for which there is a significant departure (p<0.05) from classical Mendelian segregation ratios. The far-right bar labeled “Exp.,” which shows expected genotypes and their Mendelian proportions. a. Examine Figure 4, and please explain the results. (3pts) The AA genotype is at lower frequency than expected in each of the families. Therefore, there must be selection against this genotype. b. B is dominant over A. A has a very high frequency in the population, 0.1. Assume that hatchery conditions allow all larvae to survive. What is the frequency of AA individuals in the population at this stage? If the hatchery had a population of 1000 individuals, how many would be AA? (2pts) Under Hardy-Weinberg: AA = p2 = 0.12=0.01 therefore, 10 individuals in 1000 will be AA c. Hatchery managers decide that AA individuals are reducing productivity in their culture operations and thus reducing their profit margin. If all AA individuals were removed from the larval population, what would be the fitness values of the three genotypes? Please explain. (3pts) AA = 0 AB = 1 BB = 1 The hatchery is allowing the heterozygotes to survive, therefore, they are carriers of the A allele. d. Use Allele A1 to predict the long-term effect of active removal on the frequency of the A allele. Please explain your results. Is removal a viable strategy over a 20 year period, given that oysters typically reach market size in 30 months and reproduce every three years? (3pts) It is highly unlikely that this allele will be lost over this time frame – the allele is “hiding out” in the heterozygote. e. What else could be done to eliminate the A allele? Would this be a viable approach? Use a simulation to illustrate your conclusions. (3pts) You could also remove the heterozygotes, if you were able to detect the allele. However, you might be reducing the genetic diversity at other loci and cause inbreeding. 5. Selection on homozygotes and heterozygotes The marine copepod Tisbe reticulata (a small free swimming marine crustacean) was raised under crowded conditions. T. reticulata has one gene with two alleles, V and M. Heterozygotes VM have greater survival and more offspring than both homozygotes. a. The allele V has a population frequency of 0.1. What do you predict will be the frequency of the allele after 500 generations? Perform a simulation and show whether your prediction is correct. (2pts) Neither allele is preferred in the population over the long term b. Please explain you results. Toggle between allele and genotype frequencies. (3pts) If the genotype A1A2 is the most fit, then it is maintained at a maximum at an allele frequency of 0.5. In this extreme scenario, the two homozygotes are selected against as soon as they appear. 6. Mutation as a mechanism of evolution There are 2 boxes in AlleleA1'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. Predict what will happen. 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? (3pts) The frequency of A1 declines over time (green). In a real case scenario (blue), mutation would not be a significant force on its own. 7. Mutation-selection balance Re-examine the case of allele A in oyster populations. Let’s assume that it is caused by a recessive loss-of-function mutation. a. Using AlleleA1, return all parameters to their default values. Let A2 represent the normal allele B, and let A1 represent the loss-of-function allele A. Estimate that the fitness of affected individuals is about 0.1. Set the fitness values to 0.1, 1, and 1. What is the frequency of the knockout allele A after 500 generations? Why? (2pts) The frequency is 0.00222. The allele is being carried in the heterozygote. b. The actual frequency of knockout alleles for A in populations is about 0.01. One hypothesis for the maintenance of this frequency is that new knockout alleles are continuously created by mutation. With fitness values of 0.1, 1, and 1, how high does the mutation rate from A2 to A1 need to be to achieve an equilibrium frequency of 0.01 for allele A? (2pts) mutation rate = 0.0001 c. The actual mutation rate in gene has been measured. It is high-- about 0.00011. Do you think a balance between mutation and selection is an adequate explanation for the persistence of knockout alleles at a frequency of 0.01? Pease explain. (2pts) Yes – the simulation shows that the allele is being maintained in the population at this level