Gene Interactions Chapter 6, Part b The colors of peppers are determined by the interaction of several genes. An allele Y promotes the early elimination of chlorophyll (a green pigment), whereas y does not. Allele R determines red and r determines yellow carotenoid pigments. Alleles c1 and c2 of two different genes down-regulate the amounts of carotenoids, causing the lighter shades. Orange is down-regulated red. Brown is green plus red. Pale yellow is down-regulated yellow.

12:3:1 dominant epistasis Two alleles interact but two genes are unlinked The dominant allele is epistatic For example: foxglove flowers W – confines pigments to spots D – intensity of color (D – dark red d- light red)

12:3:1 dominant epistasis practice Cross D/d;W/w x D/d;W/w W – confines pigments to spots D – intensity of color (D – dark red d- light red)

Suppressor Mutant allele that reverses the effect of a mutation of another gene resulting in a wt or almost wt phenotype Generally, the wt allele and the suppressor allele interact at the same functional level

Suppressor example “a+“ produces the normal phenotype (green) and the recessive mutant “a” results in an abnormality (yellow) Another mutant allele s, suppresses the effect of “a” and so a/a; s/s will have a wt phenotype (green) s/s can either have no effect of a+/a+ or it can produces its own abnormal phenotype (green or pink) a+ · s + wild type (green) a+ · s wild type (green or pink) a · s + original mutant (yellow) a · s wild type (green) So what if we do a dihybrid cross…what would be the predicted phenotypic ratio?

Fly suppressor genetic example In Drosophila, the recessive allele pd results in purple eye color when unsuppressed, but pd+ is wt with red eyes. A recessive allele su has no phenotype but suppresses the unlinked recessive allele pd. So pd/pd;su/su is wild type with red eyes. What would you get if you crossed a homozygous red-eyed fly with a homozygous purple eye fly? What would be your F2 progeny if you self the F1 generation? 13:3

How do suppressors work on the molecular level? Suppressors cancel the effect of a mutant allele of another gene, resulting in wild type phenotype

Modifiers Mutations at a second locus changes the degree of the expression a mutated genes at the first locus For example: How regulatory genes affect gene expression in a haploid yeast: a+ - wt gene a - low level leaky mutation b+ - wt gene b - is a down regulating mutation Regulatory genes bind to the sequence of the DNA upstream of the start site for transcription. These proteins regulate at the level of transcription

Modifier example What is the ratio here? leaky mutant a · b+ × inefficient regulator a+ · b Progeny Phenotype a+ · b+ wild type a+ · b defective (low transcription) a · b+ defective (defective protein A) a b extremely defective (low transcription of defective protein) What is the ratio here?

Modifier practice Gene b+ encodes for brown color in yeast (haploid). The mutant allele b is defective and yeast homozygous for b are white. Gene e+ is at a second locus and controls the gene expression levels of Gene b+. The mutant allele e is less effective than e+ and therefore we see a down regulation of the b locus which leads to a yellow phenotype in the presences of b+. What is the phenotypic ratio of progeny when you cross yeast with b+;e with b;e+ genotypes? 2 white: 1 yellow: 1brown

Skip problems…come back to them at the end of lecture

Synthetic lethals Two viable single mutants are intercrossed the resulting double mutants are lethal 9:3:3 ratio (the “1” dies) Seen as gene duplications or back up systems Only if defective/null mutations of both loci will result in lethality

A model for synthetic lethality 9:3:3 phenotypic ratio

Summary of variations on Mendelian Inheritance Part 1 Gene Interaction Inheritance Pattern Phenotypic ratio Additive (No gene interaction) Each genotype results in a unique phenotype (Mendel) 9:3:3:1 Complementary (Genes in same pathway) At least one dominant allele from each of the two genes need for the phenotype 9:7 Recessive Epistasis Homozygous recessive genotype at one locus masks expression at second loci 9:3:4 Dominant Epistasis Dominant allele at one locus masks expression at second locus 12:3:1 Duplicate Genes (Redundancy) One dominant allele from either of two genes needed for phenotype 15:1

Summary of variations on Mendelian Inheritance Part 2 Gene interaction Inheritance Pattern Phenotypic ratio Suppressor Mutant allele that reverses the mutation of another gene 13:3 Modifier A gene affects the expression of a second gene 1:1:1:1 (genotypic ratio) phenotypic ratio can vary Synthetic lethals Two viable single mutants that when combined result in a lethal progeny 9:3:3 (1 dies)

Penetrance and Expressivity When we use phenotype to distinguish between wt and mutant genotypes the mutation is 100% penetrant HOWEVER…many mutations show incomplete penetrance not every individual with the genotype expresses the corresponding phenotype Penetrance is the percentage of individuals with a given allele who exhibit the phenotype associated with that allele Why would an organism have a particular genotype and not express the corresponding phenotype???

3 reasons… The influence of the environment Influence of other interacting genes The subtlety of the mutant phenotype In the human pedigree of a dominant allele that is not fully penetrant… person Q has the dominant allele but does not show the associated phenotype. Q then passes the dominant allele onto some of here offspring. Since the allele is not fully penetrant, not all progeny show the trait.

Expressivity measures the degree to which a given allele is expressed at the phenotypic level aka….expressivity measures the intensity of the phenotype. Example: piebald spotting Each dog has SP The variation is caused by other loci Ten grades of piebald spotting in beagles Each of these dogs has the allele SP the allele responsible for piebald spots in dogs. The variation is caused by variations at other loci

Penetrance vs expressivity

1 2 3 5 4 Match the correct letter with the corresponding number. Answers can be used more than once or not at all. Each number may have one or more correct letters. 1 2 3 5 4 Complete penetrance or Constant expressivity Codominance Incomplete penetrance Variable expressivity Incomplete penetrance with variable expressivity

Practice problems with AA group In Drosophila melanogaster, the dominant allele Cy results in curly wings. Interestingly, however, temperature also plays a significant role on the wing phenotype. Based on this information we can say that: A) the expressivity and penetrance of the Cy allele are temperature-dependent. B) the expressivity of the Cy allele is incomplete. C) the expressivity of the Cy allele is temperature-dependent. D) the penetrance of the Cy allele is temperature-dependent. Genotype Temperature at which raised Proportion of individual with curly wings Cy+/Cy+(wild type) 17ºC 0% 26ºC Cy/Cy+ (mutant) 15% 100%

Fly suppressor genetic example In Drosophila, the recessive allele pd results in purple eye color when unsuppressed, but pd+ is wt with red eyes. A recessive allele su has no phenotype but suppresses the unlinked recessive allele pd. So pd/pd;su/su is wild type with red eyes. What would you get if you crossed a homozygous red-eyed fly (pd+/pd+;su/su) with a homozygous purple eye fly (pd/pd;su+/su+)? What would be your F2 progeny if you self the F1 generation? 13:3

What is your F1 progeny? B – Black B – brown E – no affect ee – epistatic to B locus resulting in a gold color

B – white squash regardless of “A” or “a” allele b – green when “a” is homozygous but in the presence of “A” the squash is yellow What is your F2 progeny?

A and B are duplicate genes A and B are duplicate genes. Both are able to produce red flowers but the homozygous recessive results in white flowers. What is the phenotypic ratio of this cross below?

How would you classify the following phenotype?

Blood type antigens is a big deal in pregnancies Blood type antigens is a big deal in pregnancies. What kind of expression pattern is this?

Challenge Question

Types of pathways Synthetic pathway – includes a chain of enzymes that produce (synthesize) essential molecules Signal Transduction pathway – complex signals from the environment to the genome and/or from one gene product to another gene or gene product Concept check: What is the difference between a gene and a gene product? HINT: What is another name(s) for a gene product?

Types of pathways Developmental pathways – pathways followed by genes (expression) and signaling (gene products) that a zygote uses to become an adult organism WHAT ARE THE THREE TYPES OF PATHWAYS? Synthetic Signaling Transduction Developmental Can these three pathways overlap?