DNA sequence changes of mutations in the histidine operon control region that decrease attenuation

The DNA sequence changes of 18 (9 different) mutations in the control region of the histidine operon of Salmonella typhimurium are presented. All of these mutations increase the level of expression of the operon, presumably by decreasing transcription termination at the attenuator. Five of the mutations were previously isolated hisO mutations, and the other four were isolated here as His⁺ pseudorevertants of His^- stop codon mutations in the leader peptide gene. Only two mutations, O1242 and O3154, directly affect the terminator stem of the leader RNA. One mutation, O1202, creates a strong new stem that would compete with the terminator stem. Most of the other mutations damage other RNA stems. Their effect can best be explained by, and they thus provide supporting evidence for, the prevailing model of attenuator regulation involving alternative, competing RNA stems in the leader RNA. Two mutations that do not appear to significantly affect an RNA stem directly, including a deletion of three of the seven consecutive histidine codons, are best explained as effects of a translating ribosome upon the RNA stem structures, even though the histidine codons are not translated in the pseudorevertants.