Modifications to Mendelian Inheritance I. Allelic, Genic, and Environmental Interactions

Modifications to Mendelian Inheritance I. Allelic, Genic, and Environmental Interactions A. Overview: The effect of a gene is influenced at three levels: - Intralocular (effects of other alleles at this locus) - Interlocular (effects of other genes at other loci) - Environmental (the effect of the environment on determining the effect of a gene on the phenotype) A a GENOME Environment PHENOTYPE

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions A a

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: - The presence of one allele is enough to cause the complete expression of a given phenotype.

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: - The heterozygote expresses a phenotype between or intermediate to the phenotypes of the homozygotes.

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: - Both alleles are expressed completely; the heterozygote does not have an intermediate phenotype, it has BOTH phenotypes. ABO Blood Type: A = ‘A’ surface antigens B = ‘B’ surface antigens O = no surface antigen from this locus PhenotypeGenotypes AAA, AO BBB, BO OOOAB codominance AB Phenotype

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : – the heterozygote expresses a phenotype MORE EXTREME than either homozygote TEMPEnzyme Activity “T” TEMPEnzyme Activity “t” TT = tall (grows best in warm conditions) tt = short (grows best in cool conditions) Tt = Very Tall (has both alleles and so grows optimally in cool and warm conditions)

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : 5. Lethal Alleles: - Essential genes: many proteins are required for life. “Loss-of-function” alleles may not affect heterozygotes, but in homozygotes may result in the death of the zygote, embryo, or adult – depending on when they should be expressed during development.

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : 5. Lethal Alleles: - Essential genes: many proteins are required for life. “Loss-of-function” alleles may not affect heterozygotes, but in homozygotes may result in the death of the zygote, embryo, or adult – depending on when they should be expressed during development. Recessive Lethals: Aa xAa - 25% reduction in number of offspring Aa AAAAa a aa Self-crossing the survivors shows that 1/3 show no reduction in offspring number (AA), while 2/3 show the 25% reduction in number (Aa) Why haven’t they been weeded out of the population by selection?

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : 5. Lethal Alleles: Sometimes, the heterozygote has a different phenotype than the homozygote. The phenotypic effect can be ‘dominant’ while the lethal effect is recessive. A Y exerts a dominant effect on coat color (expressed in the heterozygote), but is lethal ONLY in the homozygous condition (recessive lethality). Also an example of pleiotropy – one gene affecting >1 trait.

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : 5. Lethal Alleles: Conditional Lethality: In this case, the expression of lethality only occurs under specific conditions. Favism is caused by a mutation in the gene that codes for the enzyme glucose-6-phosphate dehydrogenase. When afflicted individuals eat fava beans, their red blood cells rupture and clog capillaries, resulting in anemia and death. It is the most common enzyme defect in humans. Why not selected against?

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : 5. Lethal Alleles: Conditional Lethality: In this case, the expression of lethality only occurs under specific conditions. Favism is caused by a mutation in the gene that codes for the enzyme glucose-6-phosphate dehydrogenase. When afflicted individuals eat fava beans, their red blood cells rupture and clog capillaries, resulting in anemia and death. It is the most common enzyme defect in humans. Why not selected against? Balanced selection… provides some protection against malaria.

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : 5. Lethal Alleles: Dominant Lethal Why aren’t they weeded out of the population?

HC is a neurodegenerative disorder caused by an autosomal lethal dominant allele. The fishing villages around Lake Maracaibo in Venezuela have the highest incidence of Huntington’s Chorea in the world, approaching 50% in some communities. The gene was mapped to chromosome 4, and the HC allele was caused by a repeated sequence of over 35 “CAG’s”. Dr. Nancy Wexler found homozygotes in Maracaibo and described it as the first truly dominant human disease (most are incompletely dominant and cause death in the homozygous condition). Dr. Nancy Wexler's work

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : 5. Lethality: 6. Multiple Alleles: - not really an interaction, but a departure from simple Mendelian postulates. - and VERY important as a source of variation # Alleles at the Locus# Genotypes Possible 1 (A)1 (AA) 2 (A, a)3 (AA, Aa, aa) 3 (A, a, A’)6 (AA, Aa, aa, A’A’, A’A, A’a)

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions 1. Complete Dominance: 2. Incomplete Dominance: 3. Codominance: 4. Overdominance : 5. Lethality: 6. Multiple Alleles: 7. Penetrance and Expressivity: - Penetrance: the percentage of individuals with a given genotype that actually EXPRESS the associated phenotype. (Because of environment or other genes) - Expressivity: The DEGREE to which an individual expresses its genetically determined trait. The degree of “eyeless” expression in Drosophila is affected by genetic background and environment.

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions - Summary and Implications: populations can harbor extraordinary genetic variation at each locus, and these alleles can interact in myriad ways to produce complex and variable phenotypes. -Consider this cross: AaBbCcDd x AABbCcDD Assume: The genes assort independently A and a are codominant B is incompletely dominant to b C is incompletely dominant to c D is completely dominant to d How many phenotypes are possible in the offspring?

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions - Summary and Implications: populations can harbor extraordinary genetic variation at each locus, and these alleles can interact in myriad ways to produce complex and variable phenotypes. -Consider this cross: AaBbCcDd x AABbCcDD Assume: The genes assort independently A and a are codominant B is incompletely dominant to b C is incompletely dominant to c D is completely dominant to d How many phenotypes are possible in the offspring? ABCD 2x3 x3 x1 = 18 If they had all exhibited complete dominance, there would have been only: 1x2 x2 x1 = 4 So the variety of allelic interactions that are possible increases phenotypic variation multiplicatively. In a population with many alleles at each locus, there is an nearly limitless amount of phenotypic variability.

I. Allelic, Genic, and Environmental Interactions A. Overview: B. Intralocular Interactions C. Interlocular Interactions The phenotype can be affected by more than one gene.

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: There may be several genes that produce the same protein product; and the phenotype is the ADDITIVE sum of these multiple genes. Creates continuously variable traits. So here, both genes A and B produce the same pigment. The double homozygote AABB produces 4 ‘doses’ of pigment and is very dark. It also means that there are more ‘intermediate gradations’ that are possible.

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: 2. Epistasis: one gene masks/modifies the expression at another locus; the phenotype in the A,B,O blood group system can be affected by the genotype at the fucosyl transferase locus. This locus makes the ‘H substance’ to which the sugar groups are added to make the A and B surface antigens. A non-function ‘h’ gene makes a non- functional foundation and sugar groups can’t be added – resulting in O blood regardless of the genotype at the A,B,O locus. This ‘O’ is called the ‘Bombay Phenotype’ – after a woman from Bombay (Mumbai) in which it was first described. Genotype at H Genotype at A,B,O Phenotype H-A-A H-B-B H-OOO H-AB hhA-O hhB-O hhOOO hhABO

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: 2. Epistasis: So, what are the phenotypic ratios from this cross: HhAO x HhBO?

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: 2. Epistasis: So, what are the phenotypic ratios from this cross: HhAO x HhBO? Well, assume they are inherited independently. AT H: ¾ H: ¼ h At A,B,O: ¼ A : ¼ O: ¼ B : ¼ AB So, the ¼ that is h is O type blood, regardless. Then, we have: ¾ H x ¼ A = 3/16 A ¾ H x ¼ O = 3/16 O (+ 4/16 above) ¾ H x ¼ B = 3/16 B ¾ H x ¼ AB = 3/16 AB Phenotypic Ratios: 3/16 A : 3/16 B : 3/16 AB : 7/16 O = 16/16 (check!)

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: 2. Epistasis: -example #2: in a enzymatic process, all enzymes may be needed to produce a given phenotype. Absence of either may produce the same alternative ‘null’. Process: enzyme 1 enzyme 2 Precursor1 precursor2 product (pigment)

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: 2. Epistasis: -example #2: in a enzymatic process, all enzymes may be needed to produce a given phenotype. Absence of either may produce the same alternative ‘null’. For example, two strains of white flowers may be white for different reasons; each lacking a different necessary enzyme to make color. Process: enzyme 1 enzyme 2 Precursor1 precursor2 product (pigment) Strain 1: enzyme 1 enzyme 2 Precursor1 precursor2 no product (white) Strain 2: enzyme 1 enzyme 2 Precursor1 precursor2 no product (white)

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: 2. Epistasis: -example #2: in a enzymatic process, all enzymes may be needed to produce a given phenotype. Absence of either may produce the same alternative ‘null’. For example, two strains of white flowers may be white for different reasons; each lacking a different necessary enzyme to make color. So there must be a dominant gene at both loci to produce color. GenotypePhenotype aaB-white aabbwhite A-bbwhite A-B-pigment So, what’s the phenotypic ratio from a cross: AaBb x AaBb ?

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: 2. Epistasis: -example #2: in a enzymatic process, all enzymes may be needed to produce a given phenotype. Absence of either may produce the same alternative ‘null’. For example, two strains of white flowers may be white for different reasons; each lacking a different necessary enzyme to make color. So there must be a dominant gene at both loci to produce color. GenotypePhenotype aaB-white aabbwhite A-bbwhite A-B-pigment So, what’s the phenotypic ratio from a cross: AaBb x AaBb ? 9/16 pigment (A-B-), 7/16 white

C. Interlocular Interactions: 1. Quantitative (Polygenic) Traits: 2. Epistasis: -example #2: in a enzymatic process, all enzymes may be needed to produce a given phenotype. Absence of either may produce the same alternative ‘null’. For example, two strains of white flowers may be white for different reasons; each lacking a different necessary enzyme to make color. So there must be a dominant gene at both loci to produce color. Indeed, by mating two strains together, we can determine whether the mutation is the result of different alleles at the same locus, or different GENES acting on one PATHWAY. This is called a complementation test.

Consider two strains that are wingless. Do these strains have different “loss of function” mutations in the same gene, or mutations in different genes involved in the same process (wing development)?

C. Interlocular Interactions 1. Quantitative (Polygenic) Traits: 2. Epistasis: -example #2: in a enzymatic process, all enzymes may be needed to produce a given phenotype. Absence of either may produce the same alternative ‘null’. -example #3: Novel Phenotypes. Comb shape in chickens is governed by 2 interacting genes that independently produce “Rose” or “Pea” combs, but together produce something completely different (walnut). GenotypePhenotype rrppsingle R-pprose rrP-pea R-P-Walnut

C. Interlocular Interactions 1. Quantitative (Polygenic) Traits: 2. Epistasis: -example #2: in a enzymatic process, all enzymes may be needed to produce a given phenotype. Absence of either may produce the same alternative ‘null’. -example #3: Novel Phenotypes. Comb shape in chickens is governed by 2 interacting genes that independently produce “Rose” or “Pea” combs, but together produce something completely different (walnut). Fruit shape in summer squash is influnced by two interacting loci, also. GenotypePhenotype aabblong A-bbsphere aaB-sphere A-B-disc

C. Interlocular Interactions 1. Quantitative (Polygenic) Traits: 2. Epistasis: In all of these cases, the observed ratios are modifications of the basic Mendelian Ratios. A-B-