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Modifier Screens
A way of exploring interactions between genes
Enhancers
Makes the phenotype more severe-less wild-type. Can be recessive enhancers (two
mutant copies required to enhance the mutant phenotype. Or dominant-one
mutant copy enhances the phenotype
Genetic enhancers have nothing to do with enhancer elements in the genome
Suppressors: make the mutant phenotype more like wild-type. Like enhancers they can be
recessive or dominant
Revertants: uncommon type, mutation in a particular gene
Intergenic suppressor bc the mutation is occuring in the same gene that was
mutated originally.
Pseudorevertants
Ex: insertion mutation (put in one, frameshift), insertion of 3, non frameshift-
restore coding template
An allelic series of white alleles - using hypomorphs to find modifiers
Often start screen with hypomorphs
Ex: start with white cherry and identify modifiers that make it more like the wildtype
or look for things that make it more like white
Start out with a hypomorphic allele of a gene that's functioning in the pathway,
partial loss of function at gene A, still activates gene B but not as it normally would.
If you have both hypomorphic mutations then it enhances the phenotype. Can say A
enhances B or B enhances A.
Apricot eyed flies
Compensatory mutations
Mutations in compensatory genes
White is a gene in the genome that is activated by a transcriptional pathway that makes
the white gene that makes the protein that allows for the production of red eyes
If we inhibit or knockout the gene that normally inhibits the transcription of white, we get
a darker apricot colored eye
Interactions of repressors are very rare
Compensatory change that then suppresses the mutant phenotype
Allele specific, gene specific
Bypass suppressor: common type
Pathway specific, rescues null allele
Mutant blocks one pathway, suppressor opens alternative pathway
Suppressors
Unc 54 mutants homozygous for the myosin heavy chain, paralyzed phenotype
Unc 54 worms were mutagenized and screened for suppressors
Worms that are homozygous for sup3 mutation among with unc54 were able to move
Sup3 encodes for myo3 which is a myosin heavy chain which is normally expressed at very
low levels but there's an upregulation of the pathway
Sup3 is an allele of myo-3 which encodes a normally minor myosin heavy chain but its
expression is increased -3 fold in the myo-3sup3 allele