Text Assignment: Chapter 3, Pages 56 - 63.
Major concepts
Important terms to learn
An abbreviated version of the material in this section was added to lecture 3 this year to facilitate use of the Virtual FlyLab for Problem Set 1. To avoid fragmentation, the original version has been left intact in these notes.
Genetic nomenclature: One potential source of confusion in the study of genetics is the diverse systems that are used for naming genes. There is general consensus that a capital letter should be used to describe a dominant allele and a lower case letter for a recessive allele. However, there is no general agreement on how to choose the symbol to represent the genetic locus in question.
Normal function vs. mutant phenotype There is an ongoing dispute as to whether a genetic locus should be named for the normal function of its gene product or for the mutant phenotype that occurs in the absence of the functional gene product. In systems where mutations that differ from a parental "wild type" are studied, it is common practice to name the locus for the mutant phentoype. Thus, for example, the white-eyed locus (w) in the fruit fly, Drosophila melanogaster, is named for loss a gene product needed for normal synthesis of eye pigment. However, in many other systems, such as yeast and bacteria, genetic loci are generally named for the normal function of the coded protein, and recessive mutants are described as lacking that function.
Genes in peas: In the case of garden peas, there is no general agreement on which system to employ. The variants that Mendel collected and analyzed were already widely used in agriculture, with no clear knowledge of their relationship to the original wild species that had been domesticated in the remote past. Mendel introduced a nomenclature of Aa, Bb, Cc, for dominance and recessiveness into his theoretical discussions (click here for an example), but he did not assign permanent letter designations to any of the specific traits that he studied.
Textbook versus notes: Our current textbook uses names based on the recessive phenotype for each locus. This appears to assume indirectly that that the recessive phenotypes correspond to mutational loss of traits from the original ancestral lines. We have already encountered this in lecture 3, where d is used to describe recessive dwarf strains and D describes the dominant tall (not dwarf) alternative. However, in many other textbooks, including those used in this course in past years, T is used to describe the dominant tall allele and the recessive short (not tall) allele is designated t. Similar differences also exist for several other alleles used in Mendel's original studies. All of the original course notes that served as the starting point for these web pages, as well as all of the review questions, old examinations, etc. prior to 1997, employ designations based on the dominant phenotypes. In view of the widespread use of both types of nomenclature and the massive effort that would be required to change everything, I have chosen not to convert all of the previously prepared materials (including parts of our current notes, such as the discussion of the forked line approach later in this lecture) to match the current textbook.
Problem loci: In theory, all seven of Mendel's original genetic loci (figure 3.1) are affected, but only four appear to be discussed sufficiently in the textbook and the notes to be potential problems:
Nature of the wrinkled mutation: As an aside, even though we are not consistently using recessive-based naming for genes in peas, there probably is a fairly strong basis for suggesting that most recessive traits reflect loss of a "wild-type" function. The first trait that Mendel described, the R (or W) gene, which is responsible for round seeds, codes for a starch-branching enzyme that affects the amount and kind of starch made in the seeds and appears to affect water retention. Seeds hat have the enzyme retain water and are stretched round, whereas seeds that lack a functional form of the enzyme are shriveled and wrinkled. (See cover picture of Cell, January 12, 1990 and article on pages 115-122 for details.)
Other species: As we move on to other species, a variety of other systems of nomemclature will be introduced, as indicated above. For example, in Drosophila melanogaster, most of the mutations that are studied have been induced by radiation or other forms of mutagenesis. A mutation that results in a recessive phenotype is designated with a lower case letter (for example, w = white eyes). However, the dominant wild type allele is referred to as + or w+. Capital letters are only used for mutations that are dominant over wild type. Because of the large number of mutations, it is often necessary to use two or three or even four letter designations. Only the first letter is capitalized for dominant mutations. The nomenclature for additional species will be introduced as the semester progresses.
Principle of Equal Segregation: As discussed in the previous lecture, each parent has two "factors" (genes or alleles) for each inherited trait, and randomly contributes one or the other to each gamete, and thus to each of its progeny. This process of segregation of alleles into gametes is strictly random.
Principle of Independent Assortment: Each unlinked gene pair assorts independently into the offspring. Thus, among offspring that have received a particular allele at one locus, there will be a random assortment of alleles at a second unlinked locus. (This is only valid for genes that are not on the same chromosome and for genes on the same chromosome that are sufficiently far apart so that crossing over makes them appear unlinked).
Mendel's "laws": The principle of equal segregation and the principle of independent assortment are sometimes referred to as Mendel's first and second "laws". However, the term "law is not really appropriate because of many exceptions due to phenomena such as linkage. Also, please note that our textbook refers to the four postulates (unit factors in pairs, dominance/recessiveness, segregation, and independent assortment) that Mendel tested and verified experimentally, but it does not reformulate them into the two basic principles (or laws) of inheritance that many other textbooks refer to. In essence, the principle of segregation incoprorates the basic concepts of unit factors in pairs, dominance/recessiveness, and equal segregation to gametes into a single principle. The principle of independent assortment corresponds quite well to the fourth postulate about independent assortment that Mendel tested and found to be valid.
Product Rule: When two independent events occur simultaneously, their combined probability is equal to the product of their individual probabilities. Thus, if one-half of the gametes of a heterozygote receive a particular allele at the first genetic locus, one-half of those gametes will receive a particular allele at a second unlinked locus. Thus, for independent assortment, the probability that a gamete will contain a specific pair of alleles from two unlinked genetic loci is 1/2 x 1/2 = 1/4.
Punnett square: The Punnett square (introduced in the previous lecture) is a convenient method for analysis of the products of independent assortment of small numbers of unlinked genes. All possible pollen or sperm haploid genomes (haplotypes) are displayed along one dimension of the square (for example, across the top) and all possible female combinations are displayed along the other dimension (for example, down the left side.) The possible diploid genotypes that can be formed by fertilization are displayed at the intersections of the vertical columns (in this case, the male contribution) with the hortizontal rows (the female contribution), together with the predicted phenotype of each. Genotypic or phenotypic ratios are then determined by counting all of the appropriate combinations. The Punnett square is a highly effective means for analyzing a dihybrid cross (figure 3.7), and also works reasonably well for a trihybrid cross (3 unlinked genes). However, it rapidly becomes extremely cumbersome as the number of unlinked events is increased.
9:3:3:1 phenotypic ratio: For a dihybrid cross (one that involves parents that are heterozygous for two unlinked loci), each parent will produce four different types of gametes. When these are combined in all possible combinations in a Punnett square, 16 different genotypic combinations are generated (figure 3.7). Because of independent assortment, 3/4 of these will exhibit the dominant phenotype for the first locus (yellow seeds) and 3/4 will also exhibit the dominant phenotype for the second locus (round seeds). Within the 3/4 with yellow seeds, there will be 3/4 whose seeds are round and 1/4 whose seeds are wrinkled. Similarly, within the 1/4 with green seeds, there will be 3/4 with round seeds and 1/4 with wrinkled seeds. When all of the multiplication is done, 9/16 of the seeds are round and yellow, 3/16 are round and green, 3/16 are yellow and wrinkled, and 1/16 are green and wrinkled. Thus, the phenotypic ratio from a dihybrid cross is 9:3:3:1. This can be verified by counting the squares on a Punnett square. In the ilustration that follows, the genotype is shown in each square, followed by the phenotype in parenthesis.
| AB | Ab | aB | ab | |
| AB | AABB (AB) | AABb (AB) | AaBB (AB) | AaBb (AB) |
| Ab | AABb (AB) | AAbb (Ab) | AaBb (AB) | Aabb (Ab) |
| aB | AaBB (AB) | AaBb (AB) | aaBB (aB) | aaBb (aB) |
| ab | AaBb (AB) | Aabb (Ab) | aaBb (aB) | aabb (ab) |
Forked line approach: For three or more unlinked events, Punnett squares, which do a complete genotypic analysis, tend to become quite cumbersome. With three unlinked genes, each parent can produce 8 different types of gametes, which generates 64 possible genotypic combinations, each depicted as a separate cell within the Punnett square. For four unllnked markers, there are 16 possible gametes from each parent and 256 cells in the complete Punnett square. It is therefore generally more effective to use the forked line approach, which is based on phenotypic, rather than genotypic, distributions. Each branch point represents the expected distribution of phenotypes at a particular locus. Multiplying the expected distributions at each of the branches across the diagram provides an easy calculation of the expected frequency of any particular phenotypic combination. An example is given below for parents that are heterozygous at three unlinked loci in peas. Although this cross is set up so that each locus yields a 3:1 phenotypic ratio, other crosses can also be employed, such as a test cross (heterozygote x homozygous recessive) at one of the loci, which would yield a 1:1 ratio at that particular branch.
3/4 Full = 27/64 YRF phenotype
/
3/4 Round
/ \
/ 1/4 constricted = 9/64 YRf phenotype
/
3/4 Yellow
/ \
/ \ 3/4 Full = 9/64 YrF phenotype
/ \ /
/ 1/4 Wrinkled
/ \
/ 1/4 constricted = 3/64 Yrf phenotype
/
YyRrFf x YyRrFf
\
\ 3/4 Full = 9/64 yRF phenotype
\ /
\ 3/4 Round
\ / \
\ / 1/4 constricted = 3/64 yRf phenotype
\ /
1/4 green
\
\ 3/4 Full = 3/64 yrF phenotype
\ /
1/4 wrinkled
\
1/4 constricted = 1/64 yrf phenotype .
27:9:9:9:3:3:3:1 ratio:. As can be seen in the forked line diagram above, a trihybrid cross yields a phenotypic ratio of 27:9:9:9:3:3:3:1. This reflects the phenotypes generated by the 64 genotypic combinations resulting from 8 different male gametes fertilizing 8 different female gametes.