Lessons from bacteriophages part 1: Deriving utility from protein structure, function, and evolution

Abstract

Historically, some of the most fundamental discoveries of modern molecular biology were revealed by examination of phage-infected cells. Some examples include the use of bacteriophage T2 to show that DNA, not protein, was the genetic material by Hershey and Chase in 1952. Crick and colleagues showed that codons are degenerate and encode for single amino acids by making use of T4 bacteriophage. Brenner and colleagues discovered that mRNA acts as the messenger in relaying the information from DNA to ribosomes with the aid of bacteriophage T2. Szybalski and colleagues demonstrated the semiconservative mechanism of DNA replication using λ phage. Restriction modification, a bacterial innate immune system that evolved as protection against invading mobile genetic elements such as plasmids and phages, was discovered in bacteriophage-infected cells. Restriction mapping was crucial for the completion of the human genome project. The mechanism of action of heat shock genes—which encode for molecular chaperones such as dnaK , dnaJ , and grpE , as well as the groE gene locus, which encodes for the molecular chaperones GroES and GroEL—were discovered in λ phage–infected Escherichia coli. The first capsid assembly inhibitor, the fluorescent dye 4,4’–bis(1-anilinonaphthalene-8-sulfonic acid) (bisANS), was discovered in experiments investigating assembly of phage P22. These are just some of the examples of contributions made by bacteriophage research in the past few decades. Here, we discuss additional discoveries derived from studies of phages.