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Life Sciences => Physiology & Medicine => Topic started by: thedoc on 15/05/2014 16:53:32

Title: Can the DNA alphabet be extended?
Post by: thedoc on 15/05/2014 16:53:32
A new pair of artificial DNA letters have been engineered into bacteria by US scientists.

Read the whole story on our  website by clicking here (http://www.thenakedscientists.com/HTML/news/news/1000496/)

  
Title: Re: Can the DNA alphabet be extended?
Post by: evan_au on 16/05/2014 11:08:03
As I understand it, synthetic biologists have added two new letters in the DNA alphabet.
These two new letters are copied across into new DNA strands as the cell divides.

I expect the next challenges are:
This is a significant proof of concept, but it opens up a web of additional challenges which must be solved before it can be used for real benefit (apart from "signing" genetically engineered DNA).

It does mean that any new cells (or animals) using these new letters would have trouble breeding with others that are unable to transcribe these new letters.
Title: Re: Can the DNA alphabet be extended?
Post by: cheryl j on 29/05/2014 01:43:04
I listened to a story about this on the CBC. It really made me wonder if there isn't some sticking point - why wouldn't nature have already come up with it with billions of years of evolution? Why aren't their different types of genetic material?
Title: Re: Can the DNA alphabet be extended?
Post by: evan_au on 29/05/2014 22:22:07
Quote
Why aren't there different types of genetic material [in nature]?
There are 4 base nucleotides in DNA (represented by the letters C, A, T, G), and a triplet of these is a codon (http://en.wikipedia.org/wiki/Codon) (AAA - TTT). With this structure you can make 64 different combinations: 4x4x4=64. This is more than enough to select the 20-22 amino acids used in bacteria, plants, animals and mitochondria, plus a few codons used for "punctuation" (eg a "stop" symbol)*.

There are already enough different codons to select perhaps 60 amino acids, but life on Earth is not using 60 amino acids, and several codons actually code for the same amino acid. If there were 60 amino acids in use, the cell would need to generate significant quantities of 60 amino acids, rather than the current 20, to use the extra combinations. It's not clear what benefits these extra proteins would bring to a protein or enzyme.

With 2 extra letters, there are now 6 base nucleotides in this artificial DNA, and a triplet of these allows 216 different combinations: 6x6x6=216. But this means that a cell must now have around 200 amino-acid-carrying Transfer RNAs floating around near the ribosome, instead of the current 60 or so. The ribosome must also "try" a lot more tRNAs before it finds the "right" one, slowing down protein synthesis.

So perhaps it is a tradeoff between flexibility and speed?

Some people have suggested that with more combinations, DNA could include an error-correcting code to cope with mutations - but this introduces frightful complexity in to the ribosome. It also does not deal with currently-uncorrectable errors like double-stranded breaks. Plus, radiodurans (http://en.wikipedia.org/wiki/Deinococcus_radiodurans) seems to survive quite well with existing DNA repair mechanisms.

* There have been some recent suggestions that the different triplets coding for the same amino acid may help with protein construction: If there are multiple tRNAs which select the same amino acid, but the tRNAs had different concentration near the ribosome, then there would be a "fast" and a "slow" version of the same amino acid. Placing "pauses" in the production of proteins may help with folding of the protein, or with regulating the production rate.