Dissection of Genetic Pathways in C. elegans - Caenorhabditis Elegans: Molecular Genetics and Development - page 124

Fig. 4 The choice of starting mutations affects the types of mutations recovered from suppressor
screens. (i) A suppressor screen using a loss-of-function (lf) mutation as a starting mutation allows
isolation of mutations (A) in genes that bypass the gene of interest, gain-of-function (gf) mutations (B)
in downstream genes that are positively regulated by the gene of interest, and loss-of-function (lf)
mutations (C) in downstream genes that are negatively regulated by the pathway. (ii) In addition to the
similar spectrum of mutations recovered from suppression of a null mutation, suppression of a reduction-
of-function (rf) mutation can identify lf mutations (D) in upstream negative regulators and gf mutations
(E) in upstream positive regulators, and mutations (F) in direct physical interactors. (iii) Suppression of a
gf mutation can obtain awide range of mutations with attributes opposite to those identified in suppression
of a lf mutation. (For color version of this figure, the reader is referred to the web version of this topic.)
regulated by the gene of interest as well as loss-of-function (lf) mutations in down-
stream genes that are negatively regulating the pathway ( Fig. 4 i).
Suppressor screens using null mutations are in general not effective in recovering
mutations in genes acting upstream of a pathway or directly interacting with the
starting genes, because null alleles produce no protein products for upstream genes
to regulate and for direct interactors to modulate. A way to identify genes that act
upstream and direct interacting genes is to use hypomorphic alleles as the basis of a
suppressor screen.
Suppression of a Hypomorphic Allele
Suppression of hypomorphic alleles, that is, reduction-of-function (rf) mutations,
not only yields the range of mutations similar to suppression of null mutations, but
also allows recovery of mutations in upstream genes, such as lf mutations in
upstream negative regulators and gf mutations in upstream positive regulators, and
mutations in genes directly interacting with the gene of interest ( Fig. 4 ii). For
example, UNC-4, a homeodomain protein, regulates synaptic connectivity of VA
motor neurons, which mediates backward movement in C. elegans. unc-4 mutants