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Chapter 6: from gene to phenotype Fig. 6-1 Using Neurospora, Beadle & Tatum showed that genes encode enzymes and that most enzymes work in biochemical pathways • Wild-type grows on minimal medium (prototrophic) (has genes/enzymes to biosynthesize virtually all compounds required for life) • Isolated mutants that require specific nutrient in medium (auxotrophic; defective in a pathway) • Analyzed mutants to identify steps (enzymes) in the pathway Fig. 6-4 Fig. 6-4 Gene: arg-1+ arg-2+ X arg-3+ Y Z “One gene – one enzyme” hypothesis Human metabolism of phenylalanine and known mutations Fig. 6-5 Known mutations in the human phenylalanine hydroxylase gene Fig. 6-6 Consequences of mutations on protein function Recessive mutations • Partially reduce protein function (“leaky” mutations) • Abolish protein function (“null” mutations) (will be recessive if one wild-type gene copy if sufficient to support normal cell function) Dominant mutations • Haplo-insufficient mutations (one wild-type gene copy is insufficient) • Gain-of-function mutations (novel function of protein or mis-expression of gene) Mutations with no effect on protein function (“silent” mutations) Fig. 6-7 Recessive mutant allele of a haplosufficient gene Fig. 6-8 Inter-allelic interactions Incomplete dominance • heterozygote phenotype is intermediate • F2 phenotypic ratio 1:2:1 Co-dominance • both alleles produce a phenotype Example of co-dominance: ABO blood group Group Genotype A IA / IA or IA / i B IB / IB or IB / i O i / i AB IA / IB IA , IB , and i are multiple alleles of the I gene Inter-allelic interactions Incomplete dominance • heterozygote phenotype is intermediate • F2 phenotypic ratio 1:2:1 Co-dominance •both alleles produce a phenotype Lethal alleles Cross of mice heterozygous for the yellow coat color allele AY/A X AY/A 2 yellow : 1 wild type ratio results from lethality of AY/AY Fig. 6-13 Manx cat (ML/M) Fig. 6-14 pleiotropism: single gene difference can affect multiple phenotypes Example: Drosophila white mutation • lack of pigment in eye, testis sheath, Malphighian tubules • electroretinogram defects • impaired vision, resulting in behavioral deviation • change in primary structure of the white protein complementation: a test for the allelism of two recessive genes; if a wild-type phenotype results from putting both genes in a diploid, we say that the genes complement each other (i.e., they are alleles of different genes) Test: cross individuals carrying the unknown genes, and observe the phenotype of the hybrid “a/a” X “a/a” normal phenotype -genes complement -are not alleles a/a+ b/b+ recessive phenotype -fail to complement -are alleles a1/a2 Complementation of flower color mutations in Campanula Fig. 6-16 Complementation tests can be performed heterokaryons in Neurospora Fig. 6-17 w/w; m/m double mutant: is white flower - indistinguishable from w/w; m/+ mutant - gene m mutation is not apparent in the double mutant (is “masked”) w/w; m/m double mutant: is white flower - indistinguishable from w/w; m/+ mutant - gene m mutation is not apparent in the double mutant (is “masked”) Epistasis: the expression of one gene is not observed in the presence of another, non-allelic gene Gene w mutations are epistatic to gene m mutations; the product of gene m is apparently “downstream” in a pathway that includes the product of gene w. A molecular example of epistasis Epistasis implies gene interaction Fig. 6-20 Coat color in Labrador dogs is controlled by the B gene (black vs. brown pigment) and the E gene (pigment vs. none) B/-;E/- Fig. 6-21 b/b;E/- B/-;e/e Suppression: a type of epistasis whereby the expression of one gene (the “suppressor” gene) normalizes the phenotype of another gene (the suppressed gene); otherwise, the suppressor gene produces no apparent phenotype. Suppression of the purpleoid eye color by a non-allelic suppressor (su) Model for suppression interactions at the protein level Fig. 6-22 Penetrance: frequency with which a phenotype is shown by a particular genotype Expressivity: the degree of phenotype produced by a particular genotype Fig. 6-25 Variable expressivity of the pie-bald phenotype in beagles Fig. 6-26 Inheritance of a dominant, incompletely penetrant allele Fig. 6-27 Fig. 6-