title: Natural selection underlies apparent stress-induced mutagenesis in a bacteriophage infection model.
abstract: The emergence of mutations following growth-limiting conditions underlies bacterial drug resistance, viral escape from the immune system and fundamental evolution-driven events. Intriguingly, whether mutations are induced by growth limitation conditions or are randomly generated during growth and then selected by growth limitation conditions remains an open question(1). Here, we show that bacteriophage T7 undergoes apparent stress-induced mutagenesis when selected for improved recognition of its host's receptor. In our unique experimental set-up, the growth limitation condition is physically and temporally separated from mutagenesis: growth limitation occurs while phage DNA is outside the host, and spontaneous mutations occur during phage DNA replication inside the host. We show that the selected beneficial mutations are not pre-existing and that the initial slow phage growth is enabled by the phage particle's low-efficiency DNA injection into the host. Thus, the phage particle allows phage populations to initially extend their host range without mutagenesis by virtue of residual recognition of the host receptor. Mutations appear during non-selective intracellular replication, and the frequency of mutant phages increases by natural selection acting on free phages, which are not capable of mutagenesis.
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Ido
authors: I
authors: Yosef
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Rotem
authors: R
authors: Edgar
authors: Department of Energy, Joint Genome Institute, Walnut Creek, California 94598, USA.
authors: Asaf
authors: A
authors: Levy
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Gil
authors: G
authors: Amitai
authors: Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
authors: Rotem
authors: R
authors: Sorek
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Ariel
authors: A
authors: Munitz
authors: Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors: Udi
authors: 0000-0003-2169-5270
authors: U
authors: Qimron
mesh_terms: D017123:Bacteriophage T7 / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D010582:Bacteriophage lambda / Q000235:genetics / Q000502:physiology; D004261:DNA Replication; D004279:DNA, Viral; D004926:Escherichia coli / Q000235:genetics / Q000821:virology*; D016296:Mutagenesis; D009154:Mutation; D012641:Selection, Genetic; D013312:Stress, Physiological / Q000235:genetics*; D014779:Virus Replication
chemical_list: D004279:DNA, Viral