Bacteriophage Mu

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Bacteriophage Mu
Virus classification
Group: Group I (dsDNA)
Order: Caudovirales
Family: Myoviridae
Subfamily: Unassigned
Genus: Mulikevirus
Species: Enterobacteria phage Mu

Bacteriophage Mu, also known as mu phage or mu bacteriophage, is a mulikevirus (the first of its kind to be identified) of the family Myoviridae which has been shown to cause genetic transposition. It is of particular importance as its discovery in E. coli by Larry Taylor was among the first observation of insertion elements in a genome. This discovery opened up the world to an investigation of transposable elements and their effects on a wide variety of organisms. While mu was specifically involved in several distinct areas of research (Including E. coli, maize, and HIV), the wider implications of transposition and insertion transformed the entire field of genetics.[1]

Discovery[edit]

Mu phage was first discovered Larry Taylor at UC Berkeley in the late 1950s. His work continued at Brookhaven National Laboratory, where he first observed the mutagenic properties of Mu; several colonies of Hfr e. coli which had been lysogenized with Mu seemed to have a tendency to develop new nutritional markers. With further investigation, he was able to link the presence of these markers to the physical binding of Mu at a certain loci. He likened the observed genetic alteration to the ‘controlling elements’ in maize, and named the phage ‘Mu’, for mutation.[2] This, however, was only the beginning. Over the next sixty years, the complexities of the phage were fleshed out by numerous researchers and labs, resulting in a far deeper understanding of mobile DNA and the mechanisms underlying transposable elements.

Key Mu-related findings[edit]

1972-1975: Ahmad Bukhari shows that Mu can insert randomly and prolifically throughout an entire bacterial genome,[3] creating stable insertions. He also demonstrates that the reversion of the gene to its original and undamaged form is possible with the excision Mu.[4]

1979: Jim Shapiro develops a Mu inspired model for transposition involving the ‘Shapiro Intermediate,’ in which both the donor and the target undergo two cleavages and then the donor is ligated into the target, creating two replication forks and allowing for both transposition and replication.[5]

1983: Kiyoshi Mizuuchi develops a protocol for observing transposition in vitro using mini-Mu plasmids,[6] allowing for a greatly increased understanding of the chemical components of transposition.

1994-2012: Because of shared mechanisms of insertion, Mu acts as a useful organism to elucidate the process of HIV integration, eventually leading to HIV integrase inhibitors such as raltegravir in 2008.[7] Additionally, Montano et al. create a crystal structure of the Mu bacteriophage transposome,[8] allowing for a detailed understanding of the process Mu amplification.

References[edit]

  1. ^ Harshey, R. (2012). The Mu story: How a maverick phage moved the field forward. Mobile DNA, (3), 21-21.
  2. ^ Taylor AL: Bacteriophage-induced mutations in E. coli. Proc Natl Acad Sci U S A 1963, 50:1043-1051.
  3. ^ Bukhari AI, Zipser D: Random insertion of Mu-1 DNA within a single gene. Nat New Biol 1972, 236:240-243. OpenURL
  4. ^ Bukhari AI: Reversal of mutator phage Mu integration. J Mol Biol 1975, 96:87-99.
  5. ^ Shapiro JA: Molecular model for the transposition and replication of bacteriophage Mu and other transposable elements. Proc Natl Acad Sci U S A 1979, 76:1933-1937.
  6. ^ Mizuuchi K: In vitro transposition of bacteriophage Mu: a biochemical approach to a novel replication reaction. Cell 1983, 35:785-794.
  7. ^ Summa V, Petrocchi A, Bonelli F, Crescenzi B, Donghi M, Ferrara M, Fiore F, Gardelli C, Gonzalez Paz O, Hazuda DJ, Jones P, Kinzel O, Laufer R, Monteagudo E, Muraglia E, Nizi E, Orvieto F, Pace P, Pescatore G, Scarpelli R, Stillmock K, Witmer MV, Rowley M: Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J Med Chem 2008, 51:5843-5855.
  8. ^ Motano SP, Pigli YZ, Rice PA: Crystal structure of the bacteriophage Mu transpososome. Nature 2012, 491:413-417.