Gene Interaction
“Standard” interpretation
of complementation test
Hawley & Gilliland (2006) Fig. 1
Exceptions to “Non-Complementation = Allelism”
Intragenic complementation (usually allele-specific)
•Multi-domain proteins (e.g., rudimentary)
•Transvection – pairing-dependent allelic complementation (stay tuned!)
Second-Site Non-Complementation (“SSNC”)
•“Poisonous interactions” – products interact to form a toxic product
(usually allele-specific)
•“Sequestration interactions” – product of one mutation sequesters the
other to a suboptimal concentration in the cell (usually one allelespecific)
•Combined haplo-insufficiency (allele non-specific)
Intragenic complementation in multi-domain proteins
Transvection:
synapsis-dependent allele complementation
E. Lewis (1954) among BX-C mutations in Drosophila
Numerous other genes in Drosophila and similar phenomena
observed in Neurospora, higher plants, mammals
Most due to enhancer elements functioning in trans (allele-specific)
Examples of body and wing yellow allele interactions
Transvection (allele complementation)
Fig. 2 Morris, et al. (1999) Genetics 151: 633–651.
Cis-preference enhancer model
(Geyer, et al., 1990)
W
B
Br
T
y2 complements y1#8 (wing & body pigmented)
wing enhancer
body enhancer
bristle enhancer
tarsal claw enhancer
Y2 is gypsy retrotransposon
insertion at the yellow gene
Y1#8 780bp promoter deletion
Y1 ATG start codon → CTG
y2 fails to complement y1 (wing & body pale)
Penetrance and expressivity contrasted
Figure 6-26
Variable expressivity
Figure 6-27
Exceptions to “Non-Complementation = Allelism”
Intragenic complementation (usually allele-specific)
•Multi-domain proteins (e.g., rudimentary)
•Transvection – pairing-dependent allelic complementation
Second-Site Non-Complementation (“SSNC”)
•“Poisonous interactions” – products interact to form a toxic product
(usually allele-specific)
•“Sequestration interactions” – product of one mutation sequesters the
other to a suboptimal concentration in the cell (usually one allelespecific)
•Combined haplo-insufficiency (allele non-specific)
Example of a “Poisonous interaction” SSNC
Hawley & Gilliland (2006) Fig. 4
(after Stearns & Botstein (1988) Genetics 119: 249–260)
Non-complementation of
non-allelic mutations
A model for synthetic lethality
Figure 6-23
A model for recessive epistasis
Figure 6-19
Recessive epistasis due to the yellow coat mutation
Modifier: a second mutation that influences the
phenotype of another mutation. Modifiers may make a
mutant phenotype more severe (=enhancers) or less
severe (=suppressors). The modifier interactions may
either be recessive (requiring homozygosity at the
modifier locus to modify the original phenotype) or
dominant (requiring only heterozygosity at the modifier
locus to modify the original phenotype).
Suppression: a form of epistasis whereby the
expression of one mutation (the “suppressor” mutation)
normalizes the phenotype of another mutation (the
“suppressed” mutation). The suppressor mutation may
display no other phenotype.
Intragenic suppression: “pseudo-reversion”; can be same
codon or different/interacting region of gene.