This simulation assignment takes about
three hours. The activities are broken down into
five exercises, each of which can be done independently.
Please submit the answers to the questions for all
five exercises
in the text file derived from the original
workbook
(WB).
@ Graded Questions You should be able to answer these questions based on the data you collected in your workbook. These questions will be graded by your instructor. Your score will be available on the Home screen when your instructor publishes scores for this module. Click ‘Submit’ for each question to turn in your answers. WARNING: To deter cheating, different students get different versions of some graded questions. Thank you for respecting your school's honor code! Q1. If the frequency of the HbS allele is 0.8 in a population, what is the frequency of the HbA allele (assuming this is a two-allele system)? Q2. In the case study in this lab, which genotype is represented by "2pq" in the Hardy-Weinberg equation? HAamnavrnntiec HRA Sickle Cell Alleles assignment instruction In the sickle cell allele exercises, you will simulate the population genetics of the sickle cell gene in relation to the occurrence of malaria in several parts of Africa. To complete these exercises, you will use SimBio simulation software and an accompanying workbook, which you will access online. The workbook that comes with the software provides the theoretical background for the activities and the questions that you will complete and submit to the Tutor for grading. Time requirement: This simulation exercise takes about three hours. The activities are broken down into five exercises, each of which can be done independently. Please submit the answers to the questions for all five exercises in the text file derived from the original workbook (WB). Note: In some instances, you may need to include tables or diagrams in your answers. In addition, submit the answers to the ten graded questions online. You will find these questions as a separate item from the exercises in the software package. There are 10 graded questions and a written portion (WB), and both need to be provided. SEI [01 LA [4 Assignments for: Principles of Biology Il (2022/2023) BIOL207 AA FLEE (TT EY [p17] 12/31/25, 9:00am MST Lab exercises are here you fill out the questions in WB from this. © Sickle-Cell Alleles (WB) [SEES] : There are few questions here rr Graded Questions—————— the app and submitted via app. .. SimBio Virtual Labs® EvoBeaker®: Sickle-Cell Alleles NOTE TO STUDENTS: This workbook accompanies the SimBio Virtual Labs® Sickle-Cell Alleles laboratory. Only registered subscribers are authorized to use this material. Laboratory subscriptions may not be shared or transferred. Student’s Name: _________________________________ Signature: __________________________________ Date: __________________________________ This and other SimBio Virtual Labs® are accessible through SimBio’s SimUText System®. This workbook or any portion thereof may not be reproduced or used in any manner without the express written permission from the copyright holder. Students purchasing this workbook new from authorized vendors are licensed to use the associated laboratory software; however, the accompanying software license is non-transferable. © 2022, SimBio. All Rights Reserved. 1 SimBio Virtual Labs®: EvoBeaker® Sickle-Cell Alleles A WARNING FROM SIMBIO ABOUT CHEATING You should know that, among other things, we periodically tinker with the underlying models in our simulations so that the results they produce (i.e. the “right answers”) change, and we let instructors know how to recognize cheating. We hope you do not succumb to the temptation but, instead, go ahead and dive in. We’ve tried to make it a truly interesting experience and a fun way to learn. Introduction Malaria is one of the world’s most serious diseases, infecting upwards of 300 million people and killing one and a half million people each year. It is most common in Africa but occurs in warmer climates worldwide. People are infected when bitten by mosquitoes carrying certain kinds of protozoa. The malarial protozoa are released as the mosquito’s mouth parts pierce the skin of the unlucky victim. The protozoa then swim through the victim’s blood until reaching the liver. There they reproduce and emerge to infect the host’s red blood cells, after which another mosquito can suck them back up and start the cycle over again. Just about anything that would protect people from malaria would be beneficial for those who live in the malaria-prone areas of the world. And indeed, some people carry an allele of a gene that provides just such a defense. Surprisingly, this anti-malaria allele was tracked down through studies of a seemingly completely unrelated disease: sickle-cell anemia. Sickle-cell anemia is every bit as nasty as malaria. Individuals with this disease have red blood cells that curve into a sickle shape instead of remaining in the circular doughnut shape of normal red blood cells. The sickle-shaped cells tend to get stuck in small blood vessels, blocking blood flow, and halting the supply of oxygen to downstream cells. Unlike malaria, sickle-cell anemia is a genetic disease. Individuals inherit alleles that cause the disease from their parents. Sickle-cell anemia is associated with a gene that encodes part of the hemoglobin molecule (called the Hb gene). Hemoglobin is the protein in red blood cells that carries oxygen. The SimBio Virtual Labs® | Sickle-Cell Alleles © 2022, SimBio. All Rights Reserved. 2 allele for the normal hemoglobin protein is called HbA and the allele for sickle cell anemia is called HbS. People who inherit the HbS allele from both parents (i.e., have the “homozygous” genotype HbS/HbS) have a form of hemoglobin that makes their red blood cells highly prone to becoming sickle-shaped. People who inherit one sickle-cell and one normal hemoglobin allele (i.e., have the “heterozygous” genotype HbS/HbA) can experience health effects but often the effects are so minor that these people do not realize they carry the HbS allele. Although people with sickle-cell anemia typically die from the disease before they are old enough to reproduce, it is relatively common in some parts of the world. Why doesn’t natural selection eliminate the disease gene? The answer is that although the sickle-cell allele can cripple your red blood cells, it can also protect you against malaria. Having one copy of HbS (the sickle-cell allele) protects you from becoming sick from malaria. Heterozygous (HbS/HbA) red blood cells that become infected with the malaria protozoa will sickle. The body’s immune system recognizes that something is wrong with the sickled cells and disposes of them. So anyone who is heterozygous for the sickle-cell hemoglobin allele is protected from both malaria and sickle-cell anemia. In genetics lingo, this is an example of a case of “heterozygote advantage.” SimBio Virtual Labs® | Sickle-Cell Alleles © 2022, SimBio. All Rights Reserved. 3 Some Important Terms and Concepts Population Genetics The study of how the genes in populations change over time. Genes, Loci, Alleles, and Gene Pools: A Quick Review of Terms Genes are units of hereditary information composed of DNA (or sometimes RNA) sequences. Genes are found on chromosomes. The place along the chromosome where the gene is located is called the locus (plural=loci). Population geneticists often refer to genes as “loci”. Alleles are alternate versions of genes (they have different DNA sequences which may or may not code for different proteins). The total collection of genes in a population is called a gene pool. Population geneticists often focus on subsets of gene pools, such as all of the alleles at a particular locus. The Hardy-Weinberg Equation In 1908 an English mathematician (G.H. Hardy) and a German physician (W. Weinberg) independently developed a formula that can be used for estimating allele frequencies from genotype frequencies or to estimate genotype frequencies from allele frequencies (for sexually-reproducing organisms). The formula: p2 + 2pq + q2 = 1 commonly referred to as the Hardy-Weinberg equation, applies when there are two alleles of a gene. The frequency of one allele is designated p and the other is designated q. The first part of the equation (p2) gives the frequency of homozygotes of the first allele, the middle part (2pq) gives the frequency of heterozygotes, and the third part (q2) gives the frequency of homozygotes of the second allele (note: sometimes these are referred to as “Hardy-Weinberg proportions”). If you know any one of the three parts, you can deduce the other two because p + q = 1 (and thus p=1-q and q=1-p). For example, if you know the frequency of homozygotes for the first allele in a population (perhaps because all homozygotes for that allele have a distinctive trait), then you know p2. By taking the square root of that, you get p and by subtracting that value from 1 you get q. Once you know p and q, you can then plug those numbers into the Hardy-Weinberg equation to figure out the expected frequency of heterozygotes (2pq) and homozygotes for the second allele (q2). SimBio Virtual Labs® | Sickle-Cell Alleles © 2022, SimBio. All Rights Reserved. 4 The Hardy-Weinberg Theorem and Hardy-Weinberg Equilibrium The Hardy-Weinberg equation resulted from Hardy and Weinberg applying probability theory to basic Mendelian genetics. Theoreticians often apply certain “assumptions” in their models to simplify the underlying mathematics. Hardy and Weinberg assumed that populations are very large and that there is no immigration or emigration. They also assumed that individuals mate at random to produce the next generation. Given these conditions, and no mutations or selection, there will be no evolution, and populations will be at what is known as “Hardy-Weinberg equilibrium”. The frequency of any allele in a population will be the same as the frequency of that allele in the haploid gametes (the eggs and sperm) and all that will happen from one generation to the next is that the alleles will be randomly shuffled and sorted again into pairs. Given this scenario, the probability of the various combinations of alleles (genotypes) will depend entirely on the allele frequencies. One way to think about the Hardy-Weinberg theorem and Hardy-Weinberg equilibrium is to imagine a system in which alleles (e.g., A and a) are drawn in pairs from a pot. The pot contains the same allele frequencies as were present in the previous generation. This pot automatically replaces what is drawn from it so that the allele frequency composition remains constant. Applying probability theory, the chance of producing a genotype is the probability of drawing the first allele times the probability of drawing the second allele. If we substitute in p for the frequency of A and q for the frequency of a, the probability of A/A will be (p)(p) = p2. The probability of A/a will be (p)(q) and of a/A will be (q)(p) so the probability of a heterozygote (A/a or a/A) will be (p)(q)+ (q)(p) = 2pq. The probability of a/a will be (q)(q) = q2. The three probabilities must add up to 1 so p2 + 2pq + q2 = 1. This is how Hardy and Weinberg derived their famous equation. Deviations From Hardy-Weinberg Equilibrium: Natural Selection and Genetic Drift As described in the previous section, the Hardy-Weinberg theorem applies to large, random-mating populations that do not experience mutation, migration, natural selection, or random genetic drift. Given that many populations in the real world probably don’t conform to those rules, you might wonder about the utility of the Hardy-Weinberg theorem. The power of the Hardy-Weinberg theorem is that it allows us to quantify our expectations of what would happen in populations if evolution were not occurring, which allows us to compare those expectations to what we see in real populations. For example, if we suspect natural selection is acting on a particular allele or genotype in a population, we can determine allele and/or genotype frequencies in the population in one generation and then see how well the frequencies conform with the expectations of Hardy-Weinberg equilibrium in future generations. If the frequencies are not very different than the expected Hardy-Weinberg proportions, SimBio Virtual Labs® | Sickle-Cell Alleles © 2022, SimBio. All Rights Reserved. 5 that would be evidence that natural selection is not acting on that allele or that the selection pressure is too weak to detect with our data. Genetic drift: the changes in allele frequencies that are due to chance events. Genetic drift is another major factor that causes populations to evolve and thus deviate from Hardy-Weinberg equilibrium. While natural selection always has a positive effect by favoring the disproportionate propagation of beneficial alleles or genotypes, genetic drift can have a positive, neutral, or negative effect. Genetic drift is most pronounced when a population is small, because that is when chance events dominate. Going back to the “pot of alleles” example in the last section, imagine we need to create 1,000 populations of only 5 individuals each by drawing from the bottomless pot of alleles that was generated by the previous generation’s gametes. There will be a lot of variability in allele and genotype frequencies among those populations due to chance (like flipping a coin and getting 4 tails in a row). If any one of the small populations is used as the basis for a new bottomless pot of alleles, the next generation would likely be quite different than the previous one.