Among the mutations that affect the function of a protein, some allow the protein to be active at the organism’s normal temperature but inactive at either higher or lower temperatures. The former are temperature-sensitive (Ts) mutations and the latter are cold-sensitive mutations. Both are types of conditional lethal mutations. Classically, Ts mutations have been used to identify proteins encoded by specific genes. Once a Ts mutation is located on a gene, its encoded protein is identified by showing that it is temperature-sensitive in an in vitro assay.
Ts mutants are also a powerful genetic way to identify interacting proteins (see Protein-Protein Interactions) because a protein destabilized at one temperature may be stabilized by mutant versions of an interacting protein. For example, if a Ts allele of a given gene is identified, suppressors can be selected at the nonpermissive temperature. Most such suppressors have no phenotype in the absence of the first mutant allele, but some have a cold-sensitive phenotype. Then the gene responsible for the cold-sensitive phenotype can be identified, and it is a candidate for a protein that interacts functionally with the first protein, and suppressors of the cold-sensitive phenotype can be sought. Like all such suppressor analysis, these suppressors have to be allele-specific to be useful.
