Map positions and specificities of suppressor mutations in Escherichia coli K-12.

suppressor mutation (“suppressor”) can be defined as a mutation which A reverses the phenotypic effects of a second (“primary”) mutation at a different position in the genome. Suppressors may occur either inside or outside the locus containing the suppressed mutation; these are termed intragenic and external suppressors, respectively. Most external suppressors are capable of suppressing particular alleles of different loci. Several external suppressors have been shown to alter the primary structure of proteins by causing amino acid substitutions at the mutant site (BRODY and YANOFSKY 1963; NOTANI, ENGELHARDT, KONIGSBERG and ZINDER 1965; WEIGERT and GAREN 1965). The units of the genetic code, presumably base-pair triplets, have been referred to as codons, each codon determining one amino acid in a polypeptide chain. Codons which code for the normal, or wild-type, amino acids are called “sense”; a mutant codon which causes the wrong amino acid to be inserted in the polypeptide during translation is called “missense”; and a mutant codon for which the translation machinery provides no corresponding amino acid is called “nonsense” (CRICK 1963). Both missense and nonsense mutations are found among primary mutations which are genetically suppressible ( BRODY and YANOFSKY 1963; BENZER and CHAMPE 1962; GAREN and SIDDIQI 1962). When a missense or a nonsense mutation is suppressed, an amino acid is substituted in the polypeptide at the position affected by the primary mutation. The substituted amino acid may be the same as that found in the wild-type polypeptide or may be a different one which nevertheless restores function. It is generally believed that suppression takes place during the “translation” of the nucleotide sequence in messenger RNA into the amino acid sequence of the polypeptide, and not during the “transcription” of the nucleotide sequence of DNA into that of RNA. Translation of a missense codon may be ambiguous in a suppressed strain; i.e., the cell makes two forms of the polypeptide, the original mutant form and the form containing the new amino acid at the mutant site (BRODY and YANOFSKY 1963). Assuming that suppression does occur at the level of translation, it is still not clear which component of the translating (protein synthesizing) system is affected by such suppressors. YANOFSKY and ST. LAWRENCE (1960) proposed that suppression may be caused by specificity alterations in transfer RNA (T-RNA)