Phi (ϕ)X174, Genetics of

Due to its atypical characteristics, the study of bacteriophage ϕX174, a member of the Microviridae, has had a profound influence on all fields of biology, from genetics to structural biology. Its single-stranded DNA genome challenged early biochemical conventions regarding nucleic acids. The virus also appeared to encode more proteins than could be accommodated by its genome, which, like all genomes, was assumed to be organized into discrete, linear arrangement of genes. However, the genome sequence, which was the first to be determined, revealed genes within genes, or overlapping reading frames. The biophysical nature and functions of the proteins encoded in the overlapping reading frames explain their placement within these regions, providing insights into genome evolution. Although single-stranded DNA replication pathways are complex, tϕX174 pathway has been completely reconstituted in vitro. The results of genetic analyses have elucidated the morphogenetic pathway, revealing at least seven defined assembly intermediates. Due to its very rapid replication cycle, ϕX174 has recently become a powerful system for experimental evolution. Since the atomic structures of the virion and the procapsid assembly intermediate have been determined, ϕX174 is one of the few organisms in which the genetics of morphogenesis and evolution can be interpreted within a structural and biochemical context.