The effect of higher structures of macromolecules on the genetic consequences of the action of mutagens.

An explanation of some discrepancies between the known chemical data and the genetic consequences of chemical mutagenesis is proposed, based on the functional role of the higher structure of macromolecules. In a single-stranded DNA- or RNA- containing genome, some primary (induced) point mutations, even if not manifested phenotypically, can result in local disturbances of the double-helical regions. Secondary (spontaneous) mutations at the complementary site of a polynucleotide can restore the higher structure. If a certain higher structure is more significant as a selection factor than the base substitution, the secondary, phenotypically detectable, mutants can accumulate during reproduction of a mutangenized phage. The higher structure of some nucleoprotein complexes and proteins could also serve as a selection factor causing accumulation of secondary mutants.