The virtual fly lab is an educational program provided by the Electronic Desktop Project at California State University, Los Angeles, with funding from the National Science Foundation. The program makes it possible to design fruit flies (Drosophila melanogaster) that carry a variety of diverse mutations, and then to simulate matings to determine how the mutant phenotypes are inherited.
Simulation of breeding experiments: The abbreviations used to describe the mutations are deliberately made ambiguous so that you will not know in advance whether you are dealing with recessive or dominant mutations, or whether they have any special properties such as sex linkage, epistasis, or homozygous lethality. In addition, a randomization algorithm adds the expected degree of experimental error that occurs in real life matings due to the laws of probability. Thus, the results that are obtained closely simulate the results of actual breeding experiments with the mutations in question.
Problem sets: Beginning with Problem Set #6, which is due on October 20, several of the problem sets during the semester will require you to do simulated crosses using the virtual fly lab and then interpret the results. Please read the material below before attempting to use the virtual fly lab.
Access to virtual fly lab: Several alternative URLs (Universal Resource Locator = internet address) can now be used to get to the home page of the Electronic Desktop Program, which includes the Virtual FlyLab. The easiest one to remember is http://vflylab.calstatela.edu. When the home page, which is labeled "Overview" comes up, click on "virtual flylab" on the left part way down the page (you may have to scroll down to see it).
Welcome page: When you arrive at the page that says "Welcome to the Virtual FlyLab, you will be ready to proceed. If the server you have originally selected is overloaded, you may be shunted back to the page that says "Overview". If so, click on Virtual FlyLab in the lower left part of the page again and you will be automatically transferred to one of the other servers.
Using the virtual fly lab: After reading the brief introduction provided on the "Welcome" page, click on the box labeled "Design a Cross Between Two Flies. This will take you to an extended page entitled "Design and mate flies". This page allows you to work with nine different categories of mutations. Because of software limitations, you can only work with one mutation at a time within each of the categories. However, you can combine mutations from several different categories in the same experimental matings.
Designing specific crosses: Please read the basic rules at the beginning of the Design and Mate Flies page before attempting any matings. You must always start by mating a fly that exhibits a mutant phenotype with a wild type fly to generate F1 hybrids. In all cases except homozygous lethal mutations and mutations on the single X chromosome of males, the mutant strains that you start with will be homozygous. The mutant phenotype can be placed either in the male or the female. To select a particular mutation, click on the circle ("radio button") ahead of its name. A dot inside the circle confirms your choice.
Additional mutations: If you wish to work with two or more mutations simultaneously, they must be selected from different categories. The mutations you select can all be placed in the same male or female parental fly (cis-) or they can be distributed between the two parental flies (trans-). Thus, for example if you are working with white eyes and yellow body, you can put both in the same male or female fly, or you can put one in each of the parents. Note that all categories of mutations in which you do not make a choice remain wild-type.
Mating: After you have designed the parental combinations you want, scroll down to find the box labeled "Mate Designed Flies" and click on it. The results of your mating will be displayed after a short delay. If the system is extremely slow, you may find it better to come back and work with it at a later time. If the Netscape browser does not receive a response in a certain amount of time, it will display a message telling you that the URL is not available (which actually means only that it failed to receive a response within its preset waiting time). .
Reading the results: The results of the cross are displayed both visually one phenotype at a time and in a summary table. Males and females are always displayed separately. Thus, for most crosses it is necessary to add together the male and female results to obtain the total picture. This can be a bit of a bother when you are not working with sex-linkage because it requires you to analyze twice as many pieces of data. For example, a total of 16 different combinations of sex and phenotype are displayed for an autosomal three-point cross. This means that four values must be added together to obtain each class of results (parental, double crossover, and the two single crossovers).
Phenotypic ratios: In addition to showing the raw data, the table also calculates phenotypic ratios. These ratios are all relative to the least frequent phenotype which is given the value of 1.000. When interpreting these ratios, particularly for complex crosses in which the the least frequent phenotypes may only be present in very small numbers, please keep in mind that the smallest numbers in the data set are subject to the greatest amount of random variability, which can cause the ratios that are calculated to be rather badly distorted in some cases. .
Sequential generations and back crosses: When the results of a cross are displayed, you can use any of the progeny to generate a new cross, or you can do a back cross to one of the parents, which can be a test cross if one of the parents is homozygous recessive. The original mutant parents that you select during the first step will always be homozygous for the mutations they carry, with two exceptions: males will be hemizygous for sex-linked loci, and dominant lethals will be heterozygous so you have a live fly to work with. However, the progeny, which are described only by phenotype, will have genotypes that are dependent on the nature of the crosses used to generate them. This makes it very important to remember (or write down) each step in a series of sequential crosses so that you will know exactly what your expectations are in the subsequent steps. Also, in cases where lethals are involved, please remember that dead flies are not counted (most lethals act in early developmental stages).
Problems with dominant wild-type progeny: F2 progeny that exhibit the dominant wild-type phenotype in a 3:1 ratio to the recessive phenotype will be a mixture of heterozygous and homozygous genotypes in a 2:1 ratio. If you select one of these dominant F2 progeny for use in a mating the program will select one fly with a dominant phenotype at random. Just as would be true in an actual experiment, you will not know whether that fly is homozygous or heterozygous. If you repeat the mating, the program will use the same fly again. To select a different fly from the pool of dominant phenotypes, you must repeat the original cross that generated the 3:1 ratio, and again select a dominant fly. If you do this repeatedly, you will find that there is a random selection of homozygous and heterozygous dominant phenotypes in an approximate 1:2 ratio.
Planning ahead: In order to take full advantage of all of the features of the virtual fly lab and of Drosophila genetics, you will need to plan ahead. For example, if you are looking for sex linkage or trying to prove that two loci are on the same chromosome, you may find it useful to place the mutations initially in the female. This will reveal sex linkage in the F1 males (potentially confused by autosomal dominants, but they will also appear in female progeny). In autosomal dihybrid crosses, starting with double mutant females will provide you with a heterozygous male that can be test-crossed by doing a back cross to the parental female to see if the two loci stay strictly in the heterozygous male where no crossing over can occur. On the other hand, if you are testing recombination frequencies in dihybrid or trihybrid crosses, starting with the mutations in the parental male will generate a heterozygous female who can then be test- crossed to the original mutant male.
Initiating a new cross: When you finish doing all of the matings you want from a particular cross, you can return to the design and mate flies page by clicking on "Design flies" at the bottom of the results page.