MS

thesisTranslation initiation in E. coli has been studied extensively using genetic, biochemical and sequence analysis methods. These studies have given us a basic knowledge concerning the characteristics of the translation initiation signal, but have not enable us to predict with certainty which sequences will function as translation initiation signals and which will not. There are also few data indicating which translation initiation signals are "strong" and which are "weak." It seems clear that adherence to the observed concensus sequence does not guarantee that a sequence can efficiently bind ribosomes to initiate translation. A model system which may help to answer the question of what is a "good" translation initiation signal is the late operon of bacteriophage lambda. This operon contains the morphogenetic genes of the phage, and is equally transcribed from the single late promoter. Although the rates of expression of the various genes of this operon have been shown to vary by nearly 1000-fold, their functional mRNA half-lives vary by less than 2-fold. Clearly the rate of expression of the genes of this operon are under translational control. This control, however, could be exercised at the level of initiation of elongation, or both. To determine the level at which the translational control of the lambda late operon occurs, we have cloned the sequences surrounding the initiator codons of several of these genes and fused them in frame to a cloned lac z gene from Escherichia coli which lacks its own translation initiation signals. The rates of expression of these hybrid proteins correlate well with the rates of expression of the phage genes from which their translation initiation signals were cloned. They do not, however, correlate with the number of "rare" codons contributed by the phage DNA. It thus seems clear that translation initiation controls the relative rates of synthesis of the lambda late gene