The genome of bacteriophage T4: an archeological dig.

I was asked to share my reflections about an article safekeeping. I then looked at my old notebooks from the 1950s and 1960s—loose-leaf binders with the pages that appeared over 40 years ago in the 1963 Cold falling out, many undated, just lists of numbers. They Spring Harbor Symposium for Quantitative Biology. The artiwere total gibberish to me. I hid them away then and cle (Epstein et al. 1963) described the phenotypes of they eventually disappeared. To write this retrospective, 130 conditional-lethal mutants of T4, 69 amber mutants, I contacted Bill Dove, one of the Perspectives editors, and and 61 temperature-sensitive (ts) lethal mutants and he sent me a copy of the Cold Spring Harbor article. I presented a genetic map of these mutations. The mutawas relieved to find that I could still understand the tions were located in 47 different genes, 35 of which material. My friend and colleague for 50 years, Frank appeared to be involved in morphogenesis of the phage Stahl, also came to my aid and sent me copies of my particles. When these morphogenesis mutants were grant reports for 1961–1963. He also sent me our corregrown under restrictive conditions, most of the infective spondence from the 1950s and 1960s. processes appeared to continue normally; there was nuIt has been claimed that one of the tasks for the clear breakdown followed by rapid DNA synthesis and elderly is to create meaning out of what they have done cell lysis, but no viable phage were released. Only phage with their lives. I can certainly see that urge now in me, components were produced: heads, or tails, or heads and so I have approached the preparation of this article and tails, or particles lacking tail fibers. The locations with considerable interest. I have sifted through the few of these genes are not random on the linkage map. documents made available to me, and I have dug into my Genes with similar phenotypes are clustered. Mutants memories and the memories of those who collaborated defective in each of the other 12 genes showed aberrawith me in this work. tions in DNA synthesis. They also showed gross defects in cell lysis and phage component production as well. These genes also showed clustering in the genome. We THE CONTEXT argued that a significant fraction of the essential genes of T4 had been identified. In 1960, when Dick Epstein and I started to work When I received the invitation to write this Perspectives with conditional-lethal mutants, our knowledge of the article, I had almost nothing at hand except my memogenome of T4 was quite sketchy. Until 1960 we had ries. I could not find any of my reprints, and my science been living with the view that T4 had three linkage files had long since disappeared. I retired in 1990, and groups, perhaps three or more DNA molecules, which for the last 14 years I have engaged almost entirely in duplicated, recombined, and somehow assorted themnonscientific matters. I recall with some embarrassment selves properly into phage heads at maturation. Figure that 20 or so years ago the Genetics Society of America 1 is the “historical” T4 linkage map I drew for our grant asked that I give my papers to the University Library for report in 1961. It consisted basically of the three linkage groups presented by Doermann and Hill (1953), and most of the mutations were plaque morphology mutations whose phenotypic basis was not known. The lone 1Author e-mail: [email protected]