04 July 2011

Increasingly synthetic biology

Adenine, cytosine, guanine, chlorouracil – chemical evolution of the bacterial genome
LifeSciencesToday based on the materials of Freie Universitaet Berlin:
A,C,G,c– chemical evolution of a bacterium’s genomeThe genetic information of all living cells is stored in DNA consisting of four canonical nitrogenous bases – adenine (A), cytosine (C), guanine (G) and thymine (T). An international group of scientists developing a young field of life sciences – xenobiology, has succeeded in creating a bacterium in whose DNA thymine is replaced synthetic building block 5-chlorouracil (c) – a substance toxic to other organisms.

The project, coordinated by Rupert Mutzel from the Institute of Biology of the Free University of Berlin (Institut für Biologie, Freie Universität Berlin) and Philippe Marliere from Heurisko USA Inc., was attended by scientists from France and Belgium. As reported in an article published in the latest issue of the journal Angewandte Chemie International Edition (Chemical Evolution of a Bacterium's Genome), the experiments were based on a unique technology developed by Marlier and Mutzel, which allows controlling the evolution of organisms under strictly controlled conditions. For a long time, large populations of microbial cells were cultured in the presence of a toxic chemical in the nutrient medium – in this case, 5-chlorouracil – in sublethal concentration. This has led to the emergence of genetic variants that can withstand high concentrations of this substance.

In response to the appearance of such variants in the cell population, the concentration of the toxic substance in the medium increased, thus maintaining a constant selective pressure. This automated process of long-term evolution was applied to adapt the genetically modified Escherichia coli coli, unable to synthesize the natural nitrogen base thymine, to growth at increasing concentrations of 5-chlorouracil. After about 1000 generations, descendants of the original strain were obtained, who used 5-chlorouracil as a full-fledged replacement for thymine. Subsequent genome analysis revealed numerous mutations in the DNA of the adapted bacteria. The contribution of these mutations to the adaptation of cells to the halogenated base will be the subject of further research.


Chemically modified microorganisms with 5-chlorouracil instead of thymine
initially they look like a variety of fibers, 
but gradually they take the form of short sticks,
typical of the wild E. coli species.
(onlinelibrary.wiley.com)

In addition to the obvious interest that such a radical change in the chemistry of living systems represents for fundamental science, scientists consider the results of their work important for the section of synthetic biology – xenobiology. This young field of life sciences aims to create new organisms that are not found in nature and have metabolic traits optimized for energy production by alternative methods or for the synthesis of extremely expensive chemicals. It is believed that such organisms, like GMOs, pose a potential threat to natural ecosystems in the event of their "leakage" from laboratories. The real danger lies either in direct competition with wild-type organisms, or in the spread of their "synthetic" DNA.

Scientists have admitted that they cannot guarantee that engineered life forms will never get into the natural environment, just as it is impossible to completely prevent the "seepage" of radioactive isotopes occurring in the vicinity of nuclear power plants. However, synthetic organisms obtained by Marlier and Mutzel, completely dependent on the presence of substances not found in nature in the environment, or containing unnatural building blocks in their genetic material – DNA – will not be able to exchange genetic material with wild-type organisms, nor compete with them. They will simply die in the absence of a xenobiotic.

Portal "Eternal youth" http://vechnayamolodost.ru04.07.2011

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