Chapter 6, From gene to phenotype
Specific Reading Assignment. The entire chapter will be covered, with the exception of Suppressors on pp. 177-178. Crucial Figures are 1, 5, 6, 11, 12, 13, 15, 18, 19, 20. Important Figures are 2, 4, 7, 8, 9, 14, 16, 17. Review Chapter 3, pp. 70-78.
Guide and Orientation Questions
This chapter extends the coverage of topics on gene function that we first saw in Chapter 3, pp. 74-84; here we will see how gene function can sometimes be inferred from external phenotypes because it affects Mendelian ratios. Conversely, this entire chapter could be viewed as the presentation of apparent exceptions to Mendelian ratios and how they can be explained, not by failures in the basic processes of meiosis and genetic transmission, but rather by the way in which some alleles express themselves under certain conditions. These special conditions often have to do with interactions between one gene product and the environment, or between one gene product and another.
Chapter 14 covers two main areas: INTERACTIONS BETWEEN THE ALLELES OF ONE GENE discusses the phenotypic ratios that can be expected from monohybrid crosses, when the relaltionship between alleles are not the ideal Mendelian ones: 1) only two alleles, 2) one allele fully dominant over the other, and 3) both alleles equally viable. The section GENE INTERACTIONS LEAD TO MODIFIED DIHYBRID RATIOS deals with the results of crosses when the phenotypic expression of an allele depends on the genetic constitution at a different locus (dihybrid crosses).
Note that the main point you should take from this chapter is an understanding of how modified Mendelian ratios provide a glimpse into the function of genes, and how gene products interact, rather than memorizing all the possible ratios for their own sake.
A fourth topic discussed in this chapter, which also leads to the obscuring of Mendelian ratios is PENETRANCE AND EXPRESSIVITY.
***FROM GENES TO PHENOTYPES (p. 166)
Objectives. To learn: 1) That there is no one-to-one relationship between a feature and a gene. It takes many genes to define a feature, and often genes have an effect on more than one feature.
1a) Use Fig. 5-15c to give fruit shape as an example of a trait affected by many (known) genes in tomato.
1b) What would be the pleiotropic effects of a mutation in the enzyme phenylalanine hydroxylase in an individual who receives an insufficient amount of tyrosine in the diet (Fig. 3-26, and corresponding text)?
Answers to FROM GENES TO PHENOTYPES
1a) Fruit shape in tomato is affected by genes P/p, O/o, Bk/bk, F/f, and Nt/nt.
1b) Under those specific environmental conditions the patient would suffer phenylketonuria because of the accumulation of phenylalanine, and also some cretinism and hypo-pigmentation, if not complete albinism. ***
A DIAGNOSTIC TEST FOR ALLELES (pp. 456-459)
Objectives. To learn: 1) The concept of complementation. 2) (Re-visit) the concept of metabolic pathways (p.75), whereby mutations in different genes can have the same phenotype.
2a) Suppose you are interested in studying eye color in fruit flies and request stocks with different eye color mutations from all over the world. Two stocks in particular have very bright red eyes (instead of the normal brown-red). You wonder whether they are mutations in the same gene. What experiment would you carry out to test this? Assume that both stocks are homozygous, and the bright red color is due to a recessive mutation. Suggest a tentative nomenclature.
2b) What are the possible outcomes of your experiment? For each outcome describe your conclusions, how you would modify the nomenclature, and indicate the genotype of the F1.
END OF CHAPTER PROBLEM 8,
Answers to A DIAGNOSTIC TEST FOR ALLELES
2a) Let us designate one red stock r1/r1 and the other r2/r2. r1+ and r2+ are the wild-type, dominant alleles. I would cross the two stocks to each other and see whether the offspring are red-eyed or normal.
2b) If the offspring were red-eyed, that would mean that r1 and r2 fail to complement, i.e., that they are on the same gene. I would change the symbols to let r define a mutation in this gene, whose mutation causes bright red color. The genotype of the F1 would be ra/rb, where a and b are the two independently obtained mutant alleles of the same gene, the ones in stocks r1 and r2.
If the offspring were wild-type, that would mean that r1 and r2 complement each other, i.e., that they are mutations on different genes. I would leave the nomenclature as is; the genotype of the F1 would be r1 r2+/r1+ r2: the phenotype is normal because there is a wild type allele for each of the two genes.
INTERACTIONS BETWEEN THE ALLELES OF ONE GENE (459-463)
Objectives. To learn: 1) How incomplete dominance and codominance can be explained by the mode of action of a gene or by how we define the phenotype. 2) What kinds of ratios can be expected from crosses involving these types of dominance relationships. 3) The expression of visible phenotypes and lethality by certain alleles. 4) What kinds of ratios can be expected from crosses involving lethal alleles. 5) The concept of multiple alleles and how they affect the ratios from monohybrid crosses.
3) Incomplete dominance.
This section continues the discussion on gene action started in Chapter 3, DEFECTIVE PROTEINS AND DOMINANCE AND RECESSIVENESS (pp. 81-83) for the cases where a gene is not haplo-sufficient.
3a) Use the concept of Adosage effect@ to explain incomplete dominance in biochemical terms. Assume that the gene for flower color in four-o=clock plants encodes an enzyme responsible for the accumulation of a red pigment. According to this line of reasoning, what differentiates complete and incomplete dominance? (See the section in Chapter 3 mentioned above, and the corresponding Guide and Orientation questions).
END OF CHAPTER PROBLEM 11, 29,
4a) How would you distinguish between incomplete dominance and codominance? Illustrate with the sickle cell example.
4b) END OF CHAPTER PROBLEM 5
5) Lethal alleles.
5a) Propose symbols for the manx mutation in cats, and use it to illustrate the possible genotypes and phenotypes associated with this mutation. Is the manx mutation dominant or recessive?
5b) Some laboratory stocks of fruit flies have curling, rather that straight, flat wings. When two curling-wing flies are mated to each other the progeny is always in a proportion of two curling for each straight wing. When a curling wing fly is crossed to a normal fly, the progeny is always one to one. Propose symbols and explain by means of crosses.
5c) How can haplo-insufficiency in a gene lead to mutant alleles that have a dominant visible effect and are recessive lethals.
END OF CHAPTER PROBLEM 6
6) Multiple alleles.
This topic is not explicitly highlighted in the book, but it appears in variuos examples. One case is blood groups in humans, another is the pattern of leaf pigmentation in clover (Fig. 6-7) and a third is in fur pigmentation in rabbits. In this last case, the multiple alleles, or allelic series, include one normal alleles fully functional c+, a null allele, ca (albino), and several other alleles with intermediate levels of activity. In this case the relationships of dominance are such that alleles with more activity are dominant over alleles with less activity (less pigmentation). In other examples, such as that of the clover, alleles seem to be incompletely dominant.
END OF CHAPTER PROBLEMS 3, 4
Answers to INTERACTIONS BETWEEN THE ALLELES OF ONE GENE
3a) Incomplete dominance almost always involves a loss-of-function allele (null or almost null, see bottom of p. 72 and Fig. 3-29), so that in a heterozygote with the wild type allele, we can expect 50% of gene product by the rule of dosage effect. In the case of the four-o=clock plant, 50% of the enzyme leads to the accumulation of 50% of pigment and this appears as pink, or diluted red (haplo-insufficient). In cases of full dominance, 50% of enzyme would be sufficient to produce enough pigment for the flower to appear red (haplo-sufficient).
4a) Incomplete dominance always refers to a quantitative trait, with the heterozygote phenotype lying halfway between the two homozygotes. Sickling caused by the sickle cell mutation is incompletely dominant because the effect on cell shape is more severe in homozygotes that heterozygotes. Codominance refers to alleles that make qualitatively different products the ability to detect both products in the heterozygote. In A/S heterozygotes both kinds of beta globin can be observed if we carry out the appropriate test, in this case protein electrophoresis. Note that the same applies to the AB blood type.
5a) Let the mutant allele be tM and the wild type, t+. A cat tM/ t+ has the short tail, while one tM/tM would die during development.
5b) "When a curling wing fly is crossed to a normal fly, the progeny is always one to one": This result would be expected of a cross between a heterozygous (curly wing) and the homozygous recessive (normal, straight wing). Let us define the symbol Cy for the dominant curly wing, and Cy+ for the normal allele. The cross described here would then be:
To explain the first cross: "When two curling-wing flies are mated to each other the progeny is always in a proportion of two curling for each straight wing." let us note that a ratio of 2:1 could derive from a ratio of 1:2:1 (i.e., 1/4:1/2:1/4) in which the first ¼ is missing . Thus, we could explain all the observations if we further hypothesize that the Cy/Cy genotype is lethal.
5c) By definition haplo-insufficiency means that a heterozygote with one functional and one non-functional allele does not make enough product for a wild type phenotype, therefore, a null mutant allele would be dominant (or at least incompletely dominant). We only need to assume that a certain minimum amount of product is needed for survival, such that the homozygote null genotype, being below that level would be lethal. Note that there are other mechanisms, in addition to haplo-insufficiency that can explain this combination of dominant visible and recessive lethal effects.
GENE INTERACTIONS LEAD TO MODIFIED DIHYBRID RATIOS (pp. 174-182)
Objectives. To learn: 1) A few examples of how different genes may affect the same trait (See FROM GENES TO PHENOTYPES). 2) The concept of epistasis. 3) The various modified Mendelian ratios obtained from dihybrid crosses when there are gene interactions. 4) The main genes involved in one particular example, the determination of coat color in mammals.
6) Interacting genes in different pathways.
6a) What phenotypic ratios are obtained from a dihybrid cross involving loss-of-function mutations in genes controlling different pathways?
6b) Given the explanation about color peppers in p. 165, provide genotypes for all the peppers shown in that photograph.
END OF CHAPTER PROBLEM 19b&d (Ignore pathway III).
7) Interacting genes in the same pathway.
END OF CHAPTER PROBLEMS 24a, 25.
9) Coat color in a mammalian model, the mouse.
9a) The generic genotype of a brown mouse could be indicated as: a/a; b/b; C/_
Using this nomenclature, indicate the genotypes of mice with the following phenotypes: black, white, agouti, cinnamon, yellow.
9b) Suggest genotypes for the mice shown in Fig. 6-17.
Answers to GENE INTERACTIONS LEAD TO MODIFIED DIHYBRID RATIOS
6a) The F2 will typically be 9:3:3:1, the only difference from a Aregular@ ratio is that the four classes will differ from one another by the same trait (rather than two different traits). See the example of skin coloration on corn snakes.
6b) Y/_; r/r; c/c (c/c indicates either c1/c1; C2/_ or C1/_; c2/c2)
y/y; r/r; C/_
Y/_; r/r; C/_
Y/_; R/_; c/c
y/y; R/_; C/_
Y/_; R/_; C/_
9a) a/a; B/_; C/_
?/?; ?/?; c/c
A/_; B/_; C/_
A/a; b/b; C/_
9b) A/_; B/_; C/_; S/_
a/a; B/_; C/_; S/_
a/a; B/_; C/_; s/s
?/?; ?/?; c/c; ?/?
?/?; ?/?; ch/ch; ?/?
PENETRANCE AND EXPRESSIVITY (pp. 182-183)
Objectives. To learn: 1) that very often the presence of a genotype does not result in the predicted phenotype. (This was an assumption made when introducing Mendelian genetics; it is true for some genes, but it is an oversimplification for many more.)
END OF CHAPTER PROBLEM 21b&c (The two traits are caused by the same mutation).
END OF CHAPTER PROBLEMS:
PROBLEMS: 20, 26, 31
Guide and Orientation Question 1b
Guide and Orientation Question 2b