1Lecture 5: Genetic interactions and epistasisA. Epistasis in a biochemical pathwayB. Epistasis in a regulatory pathwayC. Additive interactionsD. Synergistic interactionsE. SuppressionsRead 3.14 (p60-61); 7.23 (p232-234)8.32 (p290-291); 8.5 (259-260)2What is epistasis?A gene interaction in which the effects of an allele at onegene hide the effects of alleles at another gene3Codominant blood group allelesFig. 3.4b4Molecular explanation for recessive epistasis inhuman blood groups• Two parents whoare apparentlytype O haveoffspring that istype A or B onrare occasions.• Bombayphenotype –mutant recessiveallele at secondgene (hh) masksphenotype of ABOallelesFig. 3.14b5C2redCHIF3HA1A2 BZ1BZ2GLUCOSIDEANTHOCYANINSMt1, Mt2DIHYDROFLAVONOLFLAVAN-3,4-DIOLFLAVANONECHALCONEPeonidin-3-(p-coumaroyl)-rutinoside-5-glucisideepistasis analyses (genetic interactions among different mutations)A. Flavonoid biosynthetic pathway in maizebronze26WT: RedMutations in c2, a1, a2: ColorlessMutations in bz1, bz2: bronzeDouble mutantsC2/a1: colourless-but uninformativebz1/a1: colorless-a1 comes before bz1bz2/a1: colorless-a1 comes before bz2For biosynthetic pathways, the phenotype of the earlier gene in the pathway shows in the double mutant. ie. the earlier-step mutant is epistatic to the late-step mutantDetermine relationship between a1 and c2 by feeding experiment:add flavanone (naringenin): c2+naringenin = reda1+naringenin = colorless7Fig. 7.20Biochemical Pathways4Fig. 7.238B. Regulatory pathwaysSignal A B C D gene expressionPositive action-stimulate next step. Null mutation makes insensitive to signalNegative action-represses next step. Null mutation makes the gene turned on at all time (constitutively)d-: gene expression constitutively oneven in the absence of signalb-: gene expression never turned on even in the presence of the signalb-d- = d- : constitutively onFor regulatory pathways, the phenotype of the later-acting genes shows in the double mutant. ie. the later-acting mutant is epistatic to the earlier-acting mutant59etr1wtethyleneairethyleneairctr1wt ein2EthyleneCTR1 (Kinase)EIN2triple responsectr ein2 :? For regulatory pathways, the phenotype of the later-acting genes shows in the double mutant. ie. the later-acting mutant is epistatic to the earlier-acting mutant10C. Additive pathwaysDouble mutants of dissimilar phenotypes produce a combination of both phenotypesIndicate that the two mutations are in genes acting in separate pathwaysap2-2 (flower abnormal) X gl (no trichome) ap2-2 gl double mutantabnormal flower and no trichome11ap2-2gl112D. Synergistic interactions (enhancement)Two genes may act at the same step of a pathwayOr in parallel or (redundant) pathways13ap1-1ap1-1 cal-1ap1-1 cal-110ap1-1Cal-114E. Suppression Intrgenic suppressorsExtragenic suppressorsAllele-specific suppressionSuppressors are defined classically as mutations thatcorrect the phenotypic defects of another mutationwithout restoring its wild-type sequence. Suppressorsmay be intragenic (affecting the same gene) or they maybe extragenic (affecting a different gene).15Intragenic suppressorFrameshift mutation caused by a single base insertion canbe suppressed by a second mutation that cause a singlebase deletion downstream from the first mutation.See Fig. 8.5 and p259-260.16Studies of frameshift mutations in bacteriophageT4 rIIB geneFig. 8.517Intragenic suppressorsTyrGlyWTTyrGlumut1CysGluE. colitryptophansynthasemut1 mut218Extragenic suppressorsMutation in one gene could correct the effect of a mutation inanother geneNonsense (information) suppressorMutations in genes whose protein products interact19• Nonsensesuppression– (a) Nonsensemutation thatcausesincompletenonfunctionalpolypeptide– (b) Nonsense-suppressingmutation causesaddition of aminoacid at stopcodon allowingproduction of fulllengthpolypeptide.Fig. 8.3220Extragenic suppressorsParticularly useful during genetic analyses, because they oftenidentify additional components of a biological system or
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