Wednesday, 28 March 2012

Changing the Gentic Code

Ebrahim Ghasemi, 42650227

All life possesses a genome and the nature of that life is determined by it's genome. The genome consists of DNA which is made up of four nucleotides (Adenine, Cytosine, Guanine, Thymine), a series of three of these nucleotides is called a codon (64 codons in total) with each of these codons corresponding to one of the 20 amino acids or one stop codons. These codons are then translated into their respective amino acids until a stop codon is reached. Now what would happen if an organism had a codon that it did not normally have?
E coli just chiling

In theory an organism with non-naturally occurring amino acids could be made immune to viruses at the very least. Viruses replicate basically by commandeering a cell's ribosome and the other components used for replication.“Viruses depend on the fact that their proteins are encoded by the same codons as those of their hosts”(Young, Discover magazine 2011) If the organism has unnatural codons the viruses are almost certainly not going to have those codons and as such be unable to take over.

A team led by Farren Issacs at Yale University is attempting to answer that question. To do this they have edited the genome of Escherichia coli replacing the E coli's TAG stop codon with TAA another stop codon. First the team identified all 314 TAG codons in E coli, they then created small segments of DNA that had TAA instead of TAG which they mixed into a nutrient rich solution that was swimming with viral enzymes then submerged around a billion E coli in this solution.

The first of two processes MAGE was then used. MAGE or multiplex automated genome engineering, was first used a few years ago and allows bioengineers to do in days what would have previously taken them years. Essentially a specially prepared segment of DNA is placed in a solution with the cell and then electricity is run through the solution. This causes the cell to open pores in it's membrane allowing the DNA inside. Then when the cell next undergoes mitosis it will use this new DNA in the process. The DNA can then be found in the genome of the daughter cells.

MAGE gave the researchers E coli that had some TAA codons, however to create E coli that only had TAA they would have to use another process call CAGE. CAGE or conjugative assembly genome engineering relies on the bacterial form of sex, Bacterial conjugation, where one bacteria transfers genetic material (in this case the TAA codons) to another. The researches separated the E coli into 32 groups then used CAGE until they had a strain with almost entirely TAA codons.

Once the process is complete, the researchers could assign the now unnecessary TAG codon to an amino acid (natural or otherwise) instead of a stop codon. As mentioned before this could make bacteria immune to viruses, (a great thing if that bacteria is used in the production of medicine), what else this could potentially do we can at the moment only speculate. . It should be noted that the E coli seem to suffer no effects from their lack of TAG codons, raising the question what effects the stop different codons have.



References

E.coli's genetic code has been rewritten, 2011, viewed 19th March 2012, http://www.newscientist.com/article/dn20698-e-colis-genetic-code-has-been-rewritten.html

Hacking the genome with MAGE and CAGE, 2011, viewed 19th March 2012,
http://blogs.discovermagazine.com/notrocketscience/2011/07/14/hacking-the-genome-with-a-mage-and-a-cage/

Genoms edited to free up codons, 2011, viewed 19th March 2012,
http://www.nature.com/news/2011/110714/full/news.2011.419.html

Genome engineering goes high speed, 2009, viewed 19th March 2012
http://www.wired.com/wiredscience/2009/07/cellfactories/

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