What has phage lambda ever done for us?

Shortly after the dawn of biochemical genetics, Escherichia coli K-12 replaced Neurospora crassa as the key model organism. With E. coli K-12 came another, even simpler, system: each bacterial cell contained a dormant virus (bacteriophage) called lambda (λ). Occasionally, the quiescent λ genome was activated to generate free phage particles. Thus it was discovered that phage λ propagates by two alternative pathways: lytic or lysogenic. In lysogeny, it is now known that the phage genome is integrated within the bacterial host genome and replicates passively along with it; in the lytic pathway, the λ genome replicates free from the bacterial genome, directs the production of phage capsid proteins, and kills its host to release some 100 or so new phage particles (Figure 1). The fortuitous discovery of λ early in the development of molecular biology resulted in this small virus becoming a model system for studying the molecular basis of fundamental biological processes. In this essay, we discuss how the genetic and biochemical analyses of the developmental pathways of λ proved so influential (see also Box 1). In particular, we focus on the control of gene expression; the influence of phage morphogenesis on our understanding of protein folding; and DNA recombination by homologous, illegitimate and site-specific mechanisms. Studies with λ have contributed much to our understanding of the molecular basis of these processes, their biological and evolutionary roles, and how they have been harnessed by experimenters, most particularly in the development of recombinant DNA technologies. Essay