Introductory Genetics Lecture 4 Winter 2024 PDF

BIO207H5S Introductory Genetics Winter 2024 Lecture 4 Preeti Karwal, Ph.D. Gene Interactions Gene-gene interactions take place when genes at multiple loci determine a single phenotype. This does not mean, however, that two or more genes, or their products, necessarily interact physically with one...

BIO207H5S Introductory Genetics Winter 2024 Lecture 4 Preeti Karwal, Ph.D. Gene Interactions Gene-gene interactions take place when genes at multiple loci determine a single phenotype. This does not mean, however, that two or more genes, or their products, necessarily interact physically with one another. Rather, the cellular function of numerous gene products contributes to a common process or pathway and so the development of a common phenotype. Types: 1. 2. 3. 4. Epistasis Complementary gene action Duplicate gene action Supplementary/Additive genes Since inheritance patterns based on the gene-gene interactions listed above will involve at least two genes governing a trait, so they generally manifest as alterations in dihybrid cross ratio (9:3:3:1). Epistasis Epistasis refers to a phenomenon where the expression of one gene or gene pair masks or modifies the expression of another gene or gene pair. e.g. a mutation in wingless gene (epistatic), responsible for the wing formation in Drosophila masks the mutations in crossveinless gene (hypostatic) that controls wing characteristics. e.g., inheritance of coat color in mice True breeding black mice X True breeding albino mice aaCC AAcc F1: All Agouti Mice AaCc F2: Agouti : Black: Albino 9:3:4 Molecular Basis: • Normal wild-type coat color is agouti. • Agouti (A allele) is dominant to black (a allele) hair. AA – agouti , aa – black • Expression of A gene (A/a) require C gene product in dominant form. F2 results: Genotype Ratio Phenotype A_C_ 9 Agouti A_cc 3 Albino aaC_ 3 Black aacc 1 Albino Phenotypic ratio - 9 : 3 : 4 Conclusion: Comparing both albino mice, it is clear that mutation in C gene (cc genotype) masks the mutation in A gene (aa genotype), so gene C is epistatic to A gene in recessive form → RECESSIVE EPISTASIS. Inheritance of flower colour: Molecular basis: Gene A Precursor → Gene B Pigment 1 → (Red) Pigment 2 (Blue) F2 results: Genotype Ratio Phenotype A_B_ 9 Blue A_bb 3 Red aaB_ 3 White aabb 1 White Phenotypic ratio - 9 : 3 : 4 Conclusion: The inheritance of flower colour shows recessive epistasis. Gene A is epistatic to gene B in recessive form. Dominant epistasis vs Recessive epistasis: Dominant epistasis in fruit colour in summer squash: W allele in dominant form gives white colour regardless of genotype at second locus Y. In the absence of W allele in dominant form (or ww background), Y allele in dominant form gives yellow colour, while yy gives green colour. Genotype Ratio Phenotype W_Y_ 9 White W_yy 3 White wwY_ 3 Yellow wwyy 1 Green Phenotypic ratio - 12 : 3 : 1 Conclusion: The inheritance of summer squash colour shows dominant epistasis. Gene W is epistatic to gene Y in dominant form. Occasionally, a ratio of 13:3 is also observed in certain cases of epistasis. Complementary gene interaction (Duplicate Recessive Epistasis) It is demonstrated in a cross between two true-breeding strains of white-flowered sweet peas. Phenotypic ratio – 9 : 7 Conclusion: The presence of at least one dominant allele of each of two gene pairs, A and B is essential for flowers to be purple. So, the two genes complement each other. All other genotype combinations yield white flowers because the homozygous condition of either recessive allele masks the expression of the dominant allele at the other locus. Complementation Test This test helps to determine whether two mutations associated with a specific phenotype represent two different forms of the same gene (alleles) or are variations of two different genes. No Complementation Recessive mutations, a and b occur at the same locus (Allelic mutations) Complementation Recessive mutations, a and b occur at the different locus (Non-allelic mutations) When two mutations occur in different genes, they are said to be complementary, because the heterozygote condition rescues the function otherwise lost in the homozygous recessive state. The alternative name cis-trans test describes the two central components of the test. The terms cis and trans refer to the relationship of the two mutations, with cis used to describe mutations occurring on the same chromosome and trans used to describe mutations occurring on different chromosomes. Duplicate Gene Action It is demonstrated in a cross for kernel colour in wheat: F2 results: Genotype Ratio Phenotype A_B_ 9 Coloured A_bb 3 Coloured aaB_ 3 Coloured aabb 1 No colour Gene A/Gene B Precursor → Phenotypic ratio – 15 : 1 Conclusion: The biosynthesis of red pigment near the surface of wheat seeds involves many genes, two of which we label A and B. Normal, red colouration of the wheat seeds is still maintained if function of either of these genes is lost in a homozygous mutant. It can be because the two loci’s gene products have the same (redundant) functions within the same biological pathway and so can replace each other. Pigment Supplimentary genes (Additive/Cumulative effect) Novel phenotypes often result from the interactions of two genes, as in the case of the comb shape in chickens. Two genes affect the comb characters such as shape and color in chicken. Rose gene: R or r Pea gene: P or p Rose gene, if present in R_ (RR or Rr) will produce a "rose type" comb– but ONLY if Pea gene is present in pp condition. Pea gene, if present in P_ (PP or Pp) will produce a "pea type" comb-but ONLY if Rose gene is present in rr condition. If both alleles are present in double recessive condition, (rrpp), the wild type, single comb results. Walnut comb, a novel phenotype, is produced when the genotype has at least one dominant allele of each gene (R_P_). RRpp X rrPP Rose Pea F1 : RrPp Walnut Selfing F2 results: Variable Expressivity The gene expression and the resultant phenotype are often modified through the interaction between an individual’s particular genotype and the external environment. Because of this interaction, there could be a variability in the expressivity of a given gene in the individual’s phenotype. Expressivity reflects the range of expression of the mutant genotype. When the degree of phenotypic expression in dominant or homozygous recessive form varies from one individual to another, the gene is said to have Variable Expressivity. e.g. Flies homozygous for the recessive mutant eyeless gene yield phenotypes that range from the presence of normal eyes to a partial reduction in size to the complete absence of one or both eyes. Incomplete Penetrance The percentage of individuals who show at least some degree of expression of a mutant genotype defines the penetrance of the mutation. e.g., If 15 percent of mutant flies show the wild-type appearance, the mutant gene is said to have a penetrance of 85 percent. It is incompletely penetrant. Incomplete Penetrance refers to a condition, when a trait is not manifested in the detectable phenotype despite the presence of gene. It is an extreme case of variable expressivity. e.g., Polydactyly exhibits both incomplete penetrance and variable expressivity. Presence/Absence of extra digits : Penetrance/Incomplete Penetrance Presence of extra digits in all limbs or only hands or only feet or only one limb - Variable Expressivity Incomplete Penetrance vs Variable Expressivity Some of the factors responsible for incomplete penetrance and variable expressivity may be: ▪ ▪ ▪ ▪ ▪ Effect of external environment e.g. role of diet on cholesterol level in familial hypercholesterolemia. Mosaicism for X linked characters due to X inactivation (Barr body) in females Gene-Gene interactions e.g., epistasis Effect of sex hormones e.g., Sex influenced traits Late onset diseases may show age related penetrance. TABLE 5.2 Modified dihybrid phenotypic ratios due to gene interaction Genotype A_ B_ A_ bb aa B_ aa bb 9:3:3:1 9 3 3 1 9:3:4 9 3 Ratio* 12 : 3 : 1 9:7 9 9:6:1 9 Seed shape and seed color in peas Recessive epistasis Coat color in Labrador retrievers 3 Dominant epistasis Color in squash Duplicate recessive epistasis Albinism in snails 1 Duplicate interaction — 1 Duplicate dominant epistasis — Dominant and recessive epistasis — 1 TABLE 5.2 Modified dihybrid phenotypic ratios due to gene interaction 7 6 15 : 1 13 : 3 None 4 12 15 13 3 Type of Interaction Example Discussed in Chapter *Each ratio is produced by a dihybrid cross (Aa Bb × Aa Bb). Shaded bars represent combinations of genotypes that give the same phenotype. Pleiotropy The term pleiotropy is derived from the Greek words pleio, which means "many," and tropic, which means "affecting.“ Genes that affect multiple, apparently unrelated, phenotypes are called pleiotropic genes. A mutation in a pleiotropic gene may cause a disease with a wide range of symptoms. For example, Phenylketonuria (PKU), a metabolic disorder in humans caused by a deficiency of the enzyme phenylalanine hydroxylase, which is necessary to convert the essential amino acid phenylalanine to tyrosine. A defect in the single gene that codes for this enzyme results in multiple phenotypes, including mental retardation, eczema, and pigment defects that make affected individuals lighter skinned. Pleiotropy https://www.nature.com/scitable /topicpage/pleiotropy-one-genecan-affect-multiple-traits-569/ Pleiotropy should not be confused with: Gene gene interactions like epistasis, where an interaction between two or more genes governs a trait or Polygenic traits, in which multiple genes converge to result in a single phenotype e.g., skin color phenotype. Gene 1 Gene 2 Gene 3 Trait