Transduction (genetics)

Transduction

Transduction is the process by which DNA is transferred from one bacterium to another by a virus.^[1] It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector. Transduction does not require cell-to-cell contact (which occurs in conjugation), and it is DNAase resistant (transformation is susceptible to DNAase). Transduction is a common tool used by molecular biologists to stably introduce a foreign gene into a host cell's genome.

When bacteriophages (viruses that infect bacteria) infect a bacterial cell, their normal mode of reproduction is to harness the replicational, transcriptional, and translation machinery of the host bacterial cell to make numerous virions, or complete viral particles, including the viral DNA or RNA and the protein coat.

Transduction and specialized transduction are especially important because they explain how antibiotic drugs become ineffective due to the transfer of resistant genes between bacteria. In addition, hopes to create medical methods of genetic modification of diseases such as Duschenne/Becker Muscular Dystrophy are based upon these methodologies.

Lytic and lysogenic (temperate) cycles

Transduction happens through either the lytic cycle or the lysogenic cycle.

If the lysogenic cycle is adopted, the phage chromosome is integrated (by covalent bonds) into the bacterial chromosome, where it can remain dormant for thousands of generations. If the lysogen is induced (by UV light for example), the phage genome is excised from the bacterial chromosome and initiates the lytic cycle, which culminates in lysis of the cell and the release of phage particles. The lytic cycle leads to the production of new phage particles which are released by lysis of the host.

Transduction as a method of transfer genetic material

The packaging of bacteriophage DNA has low fidelity and small pieces of bacterial DNA, together with the bacteriophage genome, may become packaged into the bacteriophage genome. At the same time, some phage genes are left behind in the bacterial chromosome.

There are generally three types of recombination events that can lead to this incorporation of bacterial DNA into the viral DNA, leading to two modes of recombination.

Generalized Transduction

Generalized transduction is the process by which any bacterial gene may be transferred to another bacterium via a bacteriophage, and typically carries only bacterial DNA and no viral DNA. In essence, this is the packaging of bacterial DNA into a viral envelope. This may occur in two main ways, recombination and headful packaging.

If bacteriophages undertake the lytic cycle of infection upon entering a bacterium, the virus will take control of the cell’s machinery for use in replicating its own viral DNA. If by chance bacterial chromosomal DNA is inserted into the viral capsid which is usually used to encapsulate the viral DNA, the mistake will lead to generalized transduction.

If the virus replicates using 'headful packaging', it attempts to fill the nucleocapsid with genetic material. If the viral genome results in spare capacity, viral packaging mechanisms may incorporate bacterial genetic material into the new virion.

The new virus capsule now loaded with part bacterial DNA continues to infect another bacterial cell. This bacterial material may become recombined into another bacterium upon infection.

When the new DNA is inserted into this recipient cell it can fall to one of three fates

1. The DNA will be absorbed by the cell and be recycled for spare parts.
2. If the DNA was originally a plasmid, it will re-circularize inside the new cell and become a plasmid again.
3. If the new DNA matches with a homologous region of the recipient cell’s chromosome, it will exchange DNA material similar to the actions in conjugation.

This type of recombination is random and the amount recombined depends on the size of the virus being used.

Specialized Transduction

Specialized transduction is the process by which genes that are near the bacteriophage genome may be transferred to another bacterium via a bacteriophage. The genes that get transferred (donor genes) always depend on where the phage genome is located on the chromosome. This second type of recombination event which is the result of mistakes in the transition from a virus' lysogenic to lytic cycle is called specialized transduction, and non-viral DNA is carried as an insertion/substitution. If a virus incorrectly removes itself from the bacterial chromosome, bacterial DNA from either end of the phage DNA may be packaged into the viral capsid. Specialized transduction leads to three possible outcomes:

1. DNA can be absorbed and recycled for spare parts.
2. The bacterial DNA can match up with a homologous DNA in the recipient cell and exchange it. The recipient cell now has DNA from both itself and the other bacterial cell.
3. DNA can insert itself into the genome of the recipient cell as if still acting like a virus resulting in a double copy of the bacterial genes.

When the partially encapsulated phage material infects another cell and becomes a "prophage" (is covalently bonded into the infected cell's chromosome), the partially coded prophage DNA is called a "heterogenote".

Esther Lederberg, Larry Morse, Herman Kalckar, Michael Yarmolinsky, and Yukinori Hirota went on to do detailed studies of Galactosemia.^[2] Specialized transduction was used in these studies for gene mapping. At about this time, Esther Lederberg, Julius Adler, and Enrico Calef were also engaged in similar research involving Maltophilia.^[3]

Example of specialized transduction is λ phages in Escherichia coli discovered by Esther Lederberg ^{[4] [5]} as well as Fertility Factor F, also discovered by Esther Lederberg ^[6].

Medical Applications

• Galactosemia
• Maltophilia
• Resistance to anti-biotic drugs
• Correcting genetic diseases by direct modification of genetic errors

RNA, DNA

Viruses with RNA genomes are not able to package DNA and so do not usually make this mistake.

Upon lysis of the host cell, the mispackaged virions containing bacterial DNA can attach to other bacterial cells and inject the DNA they have packaged, thus transferring bacterial DNA from one cell to another. This DNA can become part of the new bacterium's genome and thus be stably inherited.

More general uses of the term

More generally, transduction is the process by which genetic material, e.g. DNA or siRNA, is inserted into a cell by a virus.

Common techniques in molecular biology are the use of viral vectors (including bacteriophages), electroporation, or chemical reagents that increase cell permeability. Transfection and transformation are also common ways to insert DNA into a cell.

Discovery

Transduction was discovered by Norton Zinder and Joshua Lederberg at the University of Wisconsin–Madison in 1951.^[7] However, the mechanism of general transduction as well as specialized transduction was discovered a few years later, by Esther Lederberg; Larry Morse; E. Lively; Allan Campbell, as well as Joshua Lederberg. For a more detailed explanation and a list of publications, see ^[8].

References

1. ^ Jones, Elizabeth; Hartl, Daniel L. (1998). Genetics: principles and analysis. Boston: Jones and Bartlett Publishers. ISBN 0-7637-0489-X. 
2. ^ http://www.estherlederberg.com/Censorship/CensorshipIndex.html; click on Galactosemia]
3. ^ ibid., click on Maltophilia
4. ^ ibid., click on Lambda Phage
5. ^ http://www.estherlederberg.com/Papers.html; see publication #8
6. ^ http://www.estherlederberg.com/Censorship/CensorshipIndex.html; click on Fertility Factor F
7. ^ http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=iga.section.1363
8. ^ http://www.estherlederberg.com/Censorship/CensorshipIndex.html; and click on Transduction

External links

• MeSH Genetic+Transduction
• Overview at ncbi.nlm.nih.gov
• http://www.med.umich.edu/vcore/protocols/RetroviralCellScreenInfection13FEB2006.pdf (transduction protocol)
• Generalized and Specialized transduction at sdsu.edu
• Transduction at eMedicine Dictionary
• Generalized vs Specialized Transduction