Monday, March 03, 2003

Nature Biotechnology publishes a proposal for "DNA barcoding." The authors have this to say about potential undesireable effects:
It is evident that adding a noncoding, technical label to a transgene is unlikely to have important biological consequences for the GM organism, in that there should be no increased mutability (in particular no recombination hotspots within the technical label or the "linker" between the label and the transgene), no effect of the label on the stability or expression of the transgene per se, and no changes in overall biological fitness of the organism.

To avoid a functional conflict defined early by von Neumann in his theory of self-replicating automata, the proposed information message would be placed outside of the transgene itself; alternatively, it can be placed on an intron inside the linear molecule of the transgene. To remain linked to the transgene during organism reproduction, the DNA encoding the accompanying technical message has to be closely or directly linked to the transgene DNA, a requirement that is easy to accommodate without complicating the engineering process. Given the rate of genome evolution of multicellular organisms such as animals and plants, such a linkage will certainly be maintained for a technologically relevant period of time, provided the added segment has been engineered so as not to cause increased recombination.

To avoid any serious effect of the label on the neighboring transgene or the organism itself, the introduced segment should be engineered without the use of sequences that are known as mutation hotspots (repeats, palindromes, recombination sites, etc.) or transcription elements ("hairpins" affecting transcription, enhancers, etc.). Ultimate proof will most likely be gained only through a practical evaluation of the specific label sequences.

With regard to the potential biological implications of introducing an additional DNA fragment into an organism, we see no obvious negative consequences. The added DNA fragment of proposed size (300 or so nucleotides) will increase the total length of the DNA construct to be integrated into an organism's genome by no more than 10-20%. Unlike accompanying selectable or phenotypic markers used for genetic transformation, it does not contain information expressed by the organism, and in this regard, it should be as harmless as other noncoding DNA that is abundant in genomes of most eukaryotes.

So we'll have to see.


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