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New Letters Added to the Genetic Alphabet
- pavel_lishin 11y agoNitpick: it wouldn't be a potential 216. Some three-"letter" sequences code for the same amino acids, so instead of 4^3 (64) possible amino acids, only 20 are generated. Adding new letters doesn't change what these old words create, so I think there would only be a possible maximum of 172. (I think I did my math right, but maybe not.) (edit: thanks duaneb, had my basic bio facts wrong - codons code for amino acids, not proteins.)
- duaneb 11y agoNitpick two, codons don't encode for proteins but rather components of proteins (amino acids) that the RNA/ribosome "interprets". At least that's what my high school bio taught me.
- DDickson 11y agoSequel to GATTACA(PZ)?
- scrollaway 11y agoPAZTAGACA just rolls off the tongue.
- tosseraccount 11y agoZAZA ZAPPATACCA !
- kenj0418 11y ago18 years ago, and I just now realized the title was chosen because they are all DNA letters.
- jacob019 11y agoThe "enhanced" DNA escapes into the wild where a new pathogen spreads over earth. All life is defenseless against the bizzare genetic alphabet...
- gmarx 11y agoNot sure. The behavior you posit sounds like a virus, but the regular cells would lack the machinery to translate the artificial genes. Defenses against bacteria are mostly directed against surface proteins and these proposed organisms would have regular proteins
- Karunamon 11y agoOr a prion - not really a virus, but an agent that causes the body to misbehave, almost by accident.
- dnautics 11y agoAnd since p and z are synthesized in the lab how would this escaped organism eat?
- gherkin0 11y agoIt would have to have evolved or be designed to be able to synthesize them. https://en.wikipedia.org/wiki/Nucleotide#Synthesis https://en.wikipedia.org/wiki/Nucleotide#Synthesis
- sciencerobot 11y agoLife finds a way.
- apalmer 11y agoNot sure I understand the benefit, it's denser, on the other hand from what I understand DNA generally does have much in the way of size constraints. If I remember large swathes of DNA is inactive and there isn't selective pressure to clean up this wasted space. Coupled with the fact that it is apparently more error prone and seems to show why evolution didn't go down this path. Probabably will be very useful for synthetic purposes where there isn't too much concern about fidelity after 10 million years of copying.
- gherkin0 11y ago> Not sure I understand the benefit, it's denser, on the other hand from what I understand DNA generally does have much in the way of size constraints. I'm a layman, but they could use the new base pairs to code for unusual amino acids allowing for proteins with novel chemistry. Also, I think DNA is pretty much only used to encode information, but RNA has important chemical roles (e.g. ribozymes), and the new base pairs open up similar possibilities with that.
- jey 11y agoNeat, but extending amino acids would be even cooler. DNA is mostly "just" a string encoding for information, like binary or hexadecimal. Proteins on the other hand are the actual machines whose blueprints are written in DNA, and they're built out of amino acids. Extending the set of amino acids could extend the set of basic building blocks available to create biomolecular machines. Of course, teaching ribosomes to handle them and etc will take a lot of additional work, but identifying promising new amino acids would be a nice and major first step.
- phkahler 11y ago>> Of course, teaching ribosomes to handle them and etc will take a lot of additional work, but identifying promising new amino acids would be a nice and major first step. There are a couple other amino acids in the tree of life. The mapping from base pairs to aminos is not completely static. And then there's Selenocystine (Sec) which is coded in a very unusual way. I've often thought the redundancy in the encoding allows mutations to have no effect, so a protein that is well established and important could have a more stable encoding and new things still in flux could be more prone to evolving (less stable encoding). But I have no real data on this.
- dnautics 11y agoThat's already been done many times over. Out of hundreds executed, There are a handful of interesting ones, benzoylphenylalanine, azidophenylalanine, phenylalanine methyl ketone, and bipyalanine, but the thing is, that nature really has a good selection of amino acids to accomplish just about anything it could do. The reliable chemistries that are compatible with a water solvent are few, which is why so much organic chemistry is done in nonaqueous solvent.
- dibujante 11y agoThere are actually 84 possible combinations with 4 base pairs if you accept sequences of length < 3. However, if you assume all sequences are length 3, you still get 64 combinations. We only use 20 out of that space. And if you look at how base pairs encode to amino acids, for half of them, only the first two base pairs even matter - since it's prefix-free you can guess the amino acid if you see those two and even ignore the third. Given how underutilized this space is, I'm not convinced that increasing the domain to 216 will lead to much more than the ability to express our current amino acid space with only two base pairs.
- Terribledactyl 11y agoMinor >> Underutilized may not be the best way to think about it. There is a lot of redundancy that affords protection against mutations.
- veddox 11y agoAnd actually, even the redundancy is not complete. A recent paper showed that seemingly "redundant" variations of triplets led to a slightly different 3D folding structure of the DNA, with effects on the physiology of the cell.
- sciencerobot 11y agodid the have an effect on the translated amino acid sequence or translation? Do you have a reference?
- veddox 11y agohttp://journal.frontiersin.org/article/10.3389/fgene.2014.00140/abstract http://journal.frontiersin.org/article/10.3389/fgene.2014.00... Sorry, made a mistake in the comment above. It's not the DNA's structure that is changed, it's the resulting protein's. (Different codons slightly alter the rate of translation, leading to a different folding of the protein.)
- logfromblammo 11y agoThis sounds a lot like a story from 20 years ago, that was probably in Discover Magazine or Scientific American. The new nucleotides at that time were labeled kappa and chi. And as a point of fact, three-base segments of DNA to not have a one-to-one mapping to amino acids. I also believe that a non-standard use of one of the three stop codons can change an encoded methionine to selenomethionine, with similar special cases for other proteins using rare amino acids. Furthermore, 6^3=216, but that doesn't mean that adding a new base pair can code for that many amino acids. The original set of 4, with 64 possible codons, usually encode for 20 amino acids (excepting special cases as with selenomethionine). mRNA also employs uracil and tRNA adds hypoxanthine. These lead to "wobble pairs" which in turn allow a single tRNA to match several different-but-synonymous codons. As it stands now, every codon without a matching tRNA would be a different variety of stop codon. Now, what would be interesting to me is if the P-Z pairs could match some tRNA anticodons that translate stereoisomers of the standard 20 amino acids (or actually just the 19 that are chiral). That way, the D-(KLAKLAK)2 apoptosis promoter sequence could be synthesized directly by the ordinary transcription-translation mechanics of a cell.
- mjfl 11y agoVery interesting concept. One thing I noticed after developing several genetic algorithms on my own is that they tend to give a good creative hint at what the solution to the problem should be, which the human mind can then interpret and produce what the genetic algorithm was "trying" to approach. I wonder if the same could be true with biological evolution, that there are better ways of storing genetic information than DNA and all that, but that DNA is a good guideline to what should be done.
- gherkin0 11y agoIIRC, E.T. (from the movie) had DNA with six nucleotides.
- sciencerobot 11y agoand humans have 40 DNA memo groups (5th element)
- shiggerino 11y agoIt would have been nice if the author would have at least acknowledged that in reality they are nucleobases and not tiny, tiny letters curled up in our cell nuclei. Sure, 6-amino-5-nitro-2(1H)-pyridone and 2-amino-imidazo[1,2-a]-1,3,5-triazin-4(8H)one doesn't say much to us laymen, but just saying letters and not mentioning once what they stand for is really poor reporting.
- Roodgorf 11y agoI suppose the heading and maybe opening paragraph could be seen to give that impression, but the article makes note of the fact these are new nucleotides numerous times throughout the article. I found that pretty sufficient for showing that there are not in fact actual letters in DNA.
- Dylan16807 11y agoIt still goes the entire article without naming the chemicals, which is really annoying. And a picture of the three pairs wouldn't hurt.
- veddox 11y agoSo these guys come along, casually expand a well-established code and test it under precisely one small condition. And when this one test gives them some nice data, they say: "Hey, our stuff is better than everything all of nature has ever done!" A very intellectually stimulating endeavour no doubt, but I expect some more tests before I would call this good science. Claiming that "the new additions appear to improve the alphabet" is simply extrapolation to the nth degree. [1] Oh and by the way, when the article claims that > "the three-biopolymer system may have drawbacks, since information flows only one way, from DNA to RNA to proteins" that is not correct either. For more information, read up on epigenetics. [1] Note that this quote comes from the article, not the original paper. The original paper is not quite as cocky (at least not in the abstract, but I don't have full access).
- deleted 11y ago[deleted]
- api 11y ago"And when this one test gives them some nice data, they say: "Hey, our stuff is better than everything all of nature has ever done!"" https://en.wikipedia.org/wiki/Dunning–Kruger_effect https://en.wikipedia.org/wiki/Dunning–Kruger_effect
- MaxScheiber 11y agoSteven Benner is an expert in the field. Dunning-Kruger does not apply at all. It looks more like he's trying (EDIT: or his funding foundation is trying) to talk up his research, which is understandable.
- dnautics 11y agoIt's not him, it's the simons foundation which funds his work.
- api 11y agoI wasn't referring to anyone's expertise in the field, but to humanity's understanding of a five billion year old intelligent system. What we've done so far is impressive, but we've really only scratched the surface. It's a bit early to claim superiority. We actually do know something about why the genetic code might have only four codons, and other aspects of its structure. It gets into combinatorics and search. http://www.ncbi.nlm.nih.gov/pubmed/9732450 http://www.ncbi.nlm.nih.gov/pubmed/9732450
- MaxScheiber 11y agoI'm not convinced that this is necessarily a good idea biologically, especially after talking to a couple of my friends that are researchers in this space. However, this seems quite interesting for non-biological applications. Take cold storage, for example--with a third base pairing, we can obviously develop an even denser data storage format than with regular DNA.
- trestletech 11y agoOh, good. Bioinformatics data wasn't big enough with two bits per nucleotide.
- NoMoreNicksLeft 11y agoThis article is ignorant. >Why nature stuck with four letters is one of biology’s fundamental questions. Computers, after all, use a binary system with just two “letters” — 0s and 1s. Yet two letters probably aren’t enough to create the array of biological molecules that make up life. “If you have a two-letter code, you limit the number of combinations you get,” said Ramanarayanan Krishnamurthy, a chemist at the Scripps Research Institute in La Jolla, Calif. This simply isn't true. Even with regular DNA, the word size is 3 nucleotides long... giving you 64 instructions. If I remember my highschool biology, only some of these are even used, the rest are duplicates or unused. Binary would work too, assuming ribosomes and mRNA could expand the word size... you only need 6 bits to do the same as natural DNA. Is there something I don't know that fixes word size at 3 nucleotides?
- mbq 11y agoEven with PZ DNA would have major and minor groove rather than being a symmetrical double helix beloved by virtually all illustrators, sadly also those of pop sci articles...