Lecture 5: Genetic interactions and epistasis A. Epistasis...
Transcript of Lecture 5: Genetic interactions and epistasis A. Epistasis...
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Lecture 5: Genetic interactions and epistasis
A. Epistasis in a biochemical pathwayB. Epistasis in a regulatory pathwayC. Additive interactionsD. Synergistic interactionsE. Suppressions
Read 3.14 (p60-61); 7.23 (p232-234)8.32 (p290-291); 8.5 (259-260)
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What is epistasis?
A gene interaction in which the effects of an allele at onegene hide the effects of alleles at another gene
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Molecular 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 ABOalleles
Fig. 3.14b
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C2
red
CHI
F3H
A1 A2 BZ1
BZ2
GLUCOSIDE
ANTHOCYANINS
Mt1, Mt2
DIHYDROFLAVONOLFLAVAN-3,4-DIOL
FLAVANONECHALCONE
Peonidin-3-(p-coumaroyl)-rutinoside-5-gluciside
epistasis analyses (genetic interactions among different mutations)
A. Flavonoid biosynthetic pathway in maize
bronze
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WT: RedMutations in c2, a1, a2: ColorlessMutations in bz1, bz2: bronze
Double mutants
C2/a1: colourless-but uninformativebz1/a1: colorless-a1 comes before bz1bz2/a1: colorless-a1 comes before bz2
For 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 mutant
Determine relationship between a1 and c2 by feeding experiment:add flavanone (naringenin): c2+naringenin = red
a1+naringenin = colorless
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B. Regulatory pathways
Signal A B C D gene expression
Positive action-stimulate next step. Null mutation makes insensitive to signal
Negative action-represses next step. Null mutation makes the gene turned on at all time (constitutively)
d-: gene expression constitutively oneven in the absence of signal
b-: gene expression never turned on even in the presence of the signal
b-d- = d- : constitutively on
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 mutant 5
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etr1
wtethylene air ethyleneair
ctr1wt ein2
Ethylene CTR1 (Kinase) EIN2triple response
ctr 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 mutant
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C. Additive pathways
Double mutants of dissimilar phenotypes produce a combination of both phenotypes
Indicate that the two mutations are in genes acting in separate pathways
ap2-2 (flower abnormal) X gl (no trichome)
ap2-2 gl double mutantabnormal flower and no trichome
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D. Synergistic interactions (enhancement)
Two genes may act at the same step of a pathwayOr in parallel or (redundant) pathways
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E . Suppress ion
Intrgenic suppressors
Extragenic suppressors
Allele-specif ic suppression
Suppressors 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).
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Intragenic suppressor
Frameshift 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.
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Extragenic suppressors
Mutation in one gene could correct the effect of a mutation inanother gene
Nonsense (information) suppressorMutations in genes whose protein products interact
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• Nonsensesuppression– (a) Nonsense
mutation thatcausesincompletenonfunctionalpolypeptide
– (b) Nonsense-suppressingmutation causesaddition of aminoacid at stopcodon allowingproduction of fulllengthpolypeptide.
Fig. 8.32