Modified genetic alphabet: Chemical evolution generates bacterial strain with artificial nucleotide in its genome

July 19, 2011

( -- Evolution is based on heredity, changes to the genetic material (mutation), and the natural selection of those organisms that are best suited to the given environmental conditions. An international team led by Rupert Mutzel at the Freie Universität of Berlin has now successfully emulated one particular evolutionary process in the laboratory. As the researchers report in the journal Angewandte Chemie, they were able to generate a bacterial strain whose genetic material contains an artificial building block in place of a natural one. Their success results from a special automated cultivation technique.

DNA, the carrier of the genetic information of all cells, is based on a code consisting of four “letters”, the bases adenine, cytosine, guanine, and thymine. Thanks to their new artificial evolution process, the scientists have now been able to grow bacteria in which the thymine of DNA has been replaced with an analogue, the base 5-chlorouracil. This synthetic component is poisonous to other .

The researchers started with a genetically modified strain of the bacterium Escherichia coli that is no longer capable of producing thymine. These microorganisms were cultivated over many generations in the presence of increasing amounts of chlorouracil in a specially built apparatus. Whenever the size of the population sank below a certain level, the bacteria were given a brief dose of a chlorouracil-free, thymine-containing medium to give them a chance to recover. The concentration of chlorouracil was automatically increased whenever genetic variants of the bacteria that better tolerated this substance were produced.

In this way, the cells were always exposed to a quantity of chlorouracil that was just barely tolerable. After about 1000 generations, the microorganisms had adapted to the altered , that is, the presence of chlorouracil instead of thymine. They were able to build up their DNA with chlorouracil in place of thymine. Analysis of the genome showed that the process of adaptation resulted in many changes to the of the bacteria.

“Our results demonstrate the success of our evolutionary cultivation strategy,” says Mutzel. “In this way it should be possible to develop microorganisms that can convert chemical intermediates to pharmaceuticals or break down environmental pollutants.” Microorganisms that have DNA with synthetic building blocks may also be useful in hindering the spread of purposely or accidentally released modified cells in the environment. Such microorganisms would also be incapable of exchanging genes with their natural relatives.

Explore further: DNA size a crucial factor in genetic mutations, study finds

More information: Rupert Mutzel, Chemical Evolution of a Bacterium's Genome, Angewandte Chemie International Edition 2011, 50, No. 31, 7109–7114, Permalink to the article:

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5 / 5 (4) Jul 19, 2011
Evolution is amazing!
1.3 / 5 (6) Jul 19, 2011
And what happens if you eat them? Do you get poisoned?

If yes, then what happens when the modified bacteria spread to the environment. They would have no natural predators to eat them.
5 / 5 (6) Jul 19, 2011
But they would have no source of chlorouracil either.
2 / 5 (5) Jul 19, 2011
But they would have no source of chlorouracil either.
...that is, until they evolve a way to synthesize chlorouracil -- e.g. from thymine...
5 / 5 (4) Jul 19, 2011
...that is, until they evolve a way to synthesize chlorouracil -- e.g. from thymine...

That would be one rough synthesis. It would be easy to add Cl to the structure without removing anything, but that methyl group isn't coming off by itself; pulling a CH3 off of a larger molecule is one of the hardest things one can attempt in organic synthesis. The double bond at the point of substitution makes the elimination of the methyl group even less likely, as the leaving group will be CH3 instead of CH4 (VERY unfavourable). Those nitrogens in the ring structure are "ortho-para-directing," while the point of desired substitution is 'meta' to both of them; even if you could get the methyl group off, the Cl would end up being added to the wrong spot.

Basically, it would need to evolve its own specific enzyme for the process. Many generations would have to survive in a chlorouracil-free environment for that to happen. Not impossible, but I wouldn't hold my breath.
1 / 5 (2) Jul 20, 2011
Why they have to play with E. colli really, I dont get that, bacteria exchange info and are really dynamic in it, and how they can predict what will come out of this?
There is no such intellect yet on this Planet to predict it.

Dont play with it, this coli bacteria has been turned in lab rat for the scientists, more they use it, more other people will use the drosophila fly.
There are so much other bacteria.....
not rated yet Jul 20, 2011
Also lots of drugs now are based on changing the structures of A, T G and Y bacteria take it, and their division stops, so yes definitely this is not smart, e. coli is one of the most resistant bacteria out there having resistance to everything, it is not that invasive(most of the strains) and bad but being resistant it turns to be uncontrollable .
not rated yet Jul 20, 2011
"Such microorganisms would also be incapable of exchanging genes with their natural relatives."

Smart guy wont be so certain about that.....

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