Bacteriophage A bacteriophage (), also known informally as a ''phage'' (), is a duplodnaviria virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν ('), meaning "to devour". Bacteri ...

Mu, also known as mu phage or mu bacteriophage, is a muvirus (the first of its kind to be identified) of the family ''

Myoviridae ''Myoviridae'' is a family of bacteriophages in the order ''Caudovirales''. Bacteria and archaea serve as natural hosts. There are 625 species in this family, assigned to eight subfamilies and 217 genera. Subdivisions The subfamily ''Tevenvirinae ...

'' which has been shown to cause genetic transposition. It is of particular importance as its discovery in ''

Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...

'' by Larry Taylor was among the first observations of insertion elements in a genome. This discovery opened up the world to an investigation of

transposable elements A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Transpo ...

and their effects on a wide variety of organisms. While Mu was specifically involved in several distinct areas of research (including ''E. coli'',

maize Maize ( ; ''Zea mays'' subsp. ''mays'', from es, maíz after tnq, mahiz), also known as corn (North American and Australian English), is a cereal grain first domesticated by indigenous peoples in southern Mexico about 10,000 years ago. Th ...

, and

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

), the wider implications of transposition and insertion transformed the entire field of

genetics Genetics is the study of genes, genetic variation, and heredity in organisms.Hartl D, Jones E (2005) It is an important branch in biology because heredity is vital to organisms' evolution. Gregor Mendel, a Moravian Augustinian friar wor ...

Anatomy

Phage Mu is

nonenveloped A viral envelope is the outermost layer of many types of viruses. It protects the genetic material in their life cycle when traveling between host cells. Not all viruses have envelopes. Numerous human pathogenic viruses in circulation are encase ...

, with a head and a tail. The head has an icosahedral structure of about 54 nm in width. The neck is knob-like, and the tail is contractile with a base plate and six short terminal fibers. The

genome In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding ge ...

has been fully sequenced and consists of 36,717

nucleotide Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules wi ...

s, coding for 55 proteins.

History

Mu phage was first discovered by Larry Taylor at

UC Berkeley The University of California, Berkeley (UC Berkeley, Berkeley, Cal, or California) is a public university, public land-grant university, land-grant research university in Berkeley, California. Established in 1868 as the University of Californi ...

in the late 1950s. His work continued at

Brookhaven National Laboratory Brookhaven National Laboratory (BNL) is a United States Department of Energy national laboratory located in Upton, Long Island, and was formally established in 1947 at the site of Camp Upton, a former U.S. Army base and Japanese internment c ...

, where he first observed the

mutagenic In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...

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. 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 A transposable element (TE, transposon, or jumping gene) is a nucleic acid sequence in DNA that can change its position within a genome, sometimes creating or reversing mutations and altering the cell's genetic identity and genome size. Trans ...

and the mechanisms underlying

Key Mu-related findings

1972–1975: Ahmad Bukhari shows that Mu can insert randomly and prolifically throughout an entire bacterial genome, creating stable insertions. He also demonstrates that the reversion of the gene to its original and undamaged form is possible with the excision Mu. 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 fork In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inheritanc ...

s and allowing for both transposition and replication. 1983: Kiyoshi Mizuuchi develops a protocol for observing transposition

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

using mini-Mu

plasmids A plasmid is a small, extrachromosomal DNA molecule within a cell that is physically separated from chromosomal DNA and can replicate independently. They are most commonly found as small circular, double-stranded DNA molecules in bacteria; how ...

, 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 AIDS ("acquired immune deficiency syndrome") is caused by the human immunodeficiency virus (HIV). Individuals with HIV have what is referred to as a "HIV infection". When infected semen, vaginal secretions, or blood come in contact with the mucou ...

, eventually leading to

HIV integrase inhibitors Integrase inhibitors (INIs) are a class of antiretroviral drug designed to block the action of integrase, a viral enzyme that inserts the viral genome into the DNA of the host cell. Since integration is a vital step in retroviral replication, bloc ...

such as

raltegravir Raltegravir, sold under the brand name Isentress, is an antiretroviral medication used, together with other medication, to treat HIV/AIDS. It may also be used, as part of post exposure prophylaxis, to prevent HIV infection following potential ex ...

in 2008. Additionally, Montano et al. created a crystal structure of the Mu bacteriophage transpososome, allowing for a detailed understanding of the process Mu amplification.

References

External links

Phage Mu at ViralZone
{{Taxonbar, from=Q6930650 Myoviridae Viruses Bacteriophages