Nucleotide sequence of the operators of λ ultravirulent mutants

The nucleotide sequence of the operators of ultravirulent mutants of lambda, able to grow on host cells with elevated repressor levels, was determined. It appears that ultravirulence in lambda requires multiple mutational events at the operator sequences. OL1, OL2, and OL3 operator sites are the target of mutational changes in ultravirulent phages indicating that these sites participate in vivo in repression of the PL promoter. No changes were found in the OR3 sequence, in contrast there is a mutation in OR2 and two mutations in OR1, in both lambda 668 and lambda 2668 phages. This mutated operator structure accounts for the constitutive expression of their PR promoter either in cells overproducing the lambda repressor or in cells overproducing the cro gene product. A model of the structure of the lambda operator site is proposed. The nucleotide sequence in each site can be divided into two functionally different subsets, one of which is recognized by the repressor while the other stabilizes the repressor-operator interaction.