Talk:Synthetic DNA

Merger proposal

The following discussion is closed. Please do not modify it. Subsequent comments should be made in a new section. A summary of the conclusions reached follows.

The result of this discussion was to merge, but to Base pair. BatteryIncluded (talk) 21:57, 14 May 2014 (UTC)

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I propose that Synthetic DNA be merged into Nucleic acid analogues. This article is new, and based on hyped news around one paper and is just one part of a much bigger story that is explained in that article. There is no guarantee at all the work in the paper will be replicable, as well. Jytdog (talk) 21:48, 8 May 2014 (UTC)

• Support: FWIW - Yes - merging the Synthetic DNA article into the Nucleic acid analogues article may be a good idea I would think - at least for the moment - and until Synthetic DNA has been fully confirmed and realized - in any case - Enjoy! :) Drbogdan (talk) 23:07, 8 May 2014 (UTC)

Brief Followup - The Oxford definition of "analogue" => "Chemistry - A compound with a molecular structure closely similar to that of another" - seems this may fit the situation with the UBPs (ie, Unnatural Base Pairs) currently being discussed - are these UBPs "analogues" (by definition?) - or not - nonetheless, I remain open atm to other views and/or suggestions - esp, perhaps, some other alternative name for merging both articles? - ("Synthetic nucleic acids" proposed by MelanieN may be a worthy consideration of course) - should note that "Redirects" using ok terms, including Common Names, are always a solution to less findable, but perhaps more accurate, main article names - in any regards - Enjoy! :) Drbogdan (talk) 00:47, 9 May 2014 (UTC)

• Oppose for two reasons: 1) Work on synthetic DNA has been going on since 1989; it is not a matter of one paper. Even if that particular report gets modified or retracted, there has been plenty of other work published about synthetic DNA.[1] [2] [3] 2) The article title "Nucleic acid analogues" is not only a very unlikely search term, it is inaccurate. The "analogues" discussed are chemically nucleic acids; they are not some other compound that resembles a nuclei acid. If the articles are to be merged, it should be under some better title. (How about merging both into an article called "Synthetic nucleic acids"? Jytdog rightly pointed out (elsewhere) that this article can't be merged into "Synthetic DNA" because it talks about RNA too. Naming ithe main article "Synthetic nucleic acids" would solve that problem and would also be a reasonably findable and accurate Common Name.)--MelanieN (talk) 00:03, 9 May 2014 (UTC)

so it appears this is going to be vindicative, so I am outta here. again, sorry i insulted you. Jytdog (talk) 01:19, 9 May 2014 (UTC)

? No anger here, just offering a name that would solve the problem you raised. Does this name work for you? or some other name? --MelanieN (talk) 12:55, 9 May 2014 (UTC)

P.S. I have removed the parts of my comment that Jytdog found to be problematic. --MelanieN (talk) 19:03, 9 May 2014 (UTC)

• Oppose because the two concepts are different. Nucleic acid analogues compete with, or substitute the naturally occurring nucleobases in DNA and RNA. The new paper describes two completely new and synthetic nucleobases (called X and Y) that do not compete nor substitute the natural nucleobases (A, T, G, C, or U). THAT is the breakthrough: not an analogue doing a substitution but a new information-coding nucleobase -that is recognized by the replication enzymes.

On the other hand, synthetic DNA (which has existed for decades for decade) is simply a genetically engineered nucleic acid sequence.

My suggestion and proposal is that you consider that Synthetic DNA = Genetic engineering, which has been done for a long time. (I suppose the new X, Y nucleobases will eventually be included in the more general concept of genetic engineering if they actually get a cell system with X, Y nucleobases to transcribe a gene into a protein.) At this moment, I think that the Nature paper and Wikipedia article on the new X and Y nucleobases should be named/moved to "Synthetic nucleic acid". Cheers, BatteryIncluded (talk) 17:43, 9 May 2014 (UTC)

• Oppose per BatteryIncluded. Jim Carter ^(talk) 19:19, 9 May 2014 (UTC)

Discussion

To be clear - seems the proposed title "Synthetic nucleic acid" is a *very* general term - and would include - as possible subgroups - "Synthetic DNA", "Synthetic RNA", "Synthetic mRNA", "Synthetic rRNA", "Synthetic tRNA", - and yes - "Nucleic acid analogue" - and also perhaps - "Artificial nucleic acids analogs", "Glycol nucleic acid", "Locked nucleic acid", "Morpholino", "Peptide nucleic acid", "Threose nucleic acid" - probably others as well - does this *all* seem *entirely* ok to everyone? - or not? - in any case - Enjoy! :) Drbogdan (talk) 20:26, 9 May 2014 (UTC)

Thank you all. It looks like we are narrowing down the nomenclature. Let's forget the colloquial use of "synthetic" for a moment and acknowledge that the new X,Y nucleotides are monomers that can be introduced in DNA, a polymer:

1. Synthetic DNA ≈ genetic engineering are designed sequences of nucleotides; they are polymers and can be included in your list above.
2. Synthetic nucleotide, the subject of the Nature paper, are newly created monomers that can be linked to DNA. They are [potential] new molecules for genetic engineering. In other words, a potential new molecule to further expand DNA capabilities or an Expanded genetic code.

To recap: the 2 new molecules are not DNA (polymer) but nucleotides (monomers). If everyone agrees with this, the logical nomenclature would suggest to move the title of this Wiki article to Synthetic nucleotide, or merge with Expanded genetic code. CHeers, - BatteryIncluded (talk) 21:34, 9 May 2014 (UTC)

YES - seems the title terminology may be improving re the latest research - seems "Synthetic nucleotide" (and "Expanded genetic code") may be worth considering - perhaps as well - "Synthetic nucleoside" and "Synthetic base pair" - after selecting an ok title - we might then consider if the present "Nucleic acid analogue" and "Synthetic DNA" articles should - or should not - be included - seems the title terminology itself may be merging (so-to-speak) to some extent - in any regards - Enjoy! :) Drbogdan (talk) 22:28, 9 May 2014 (UTC)

Thank you for your input. Being that the information is yet scant and needs replication by other teams, we could simply merge it into Expanded genetic code and in the future (years?) it may have its own article. BatteryIncluded (talk) 22:47, 9 May 2014 (UTC)

Yes I agree - waiting for the new research to be verified and/or better realized seems to be in order atm - perhaps a new future article titled "Unnatural base pair" may be a consideration - such a title would accurately describe this new line of research and, as well, be consistent with the original study - adding a section to the present "Base pair" article may also be in order until then, I would think - WP:Redirects, to help better locate the material, could include some of the terminology mentioned earlier in this discussion - hope this helps in some way - Enjoy! :) Drbogdan (talk) 23:48, 9 May 2014 (UTC)

Yes, a section in Base pair is in order. And it would be standard procedure to have a "Main article" or section to link it to for further information. Hopefully, we will define and formalize it soon. Thank you, BatteryIncluded (talk) 06:49, 10 May 2014 (UTC)

I wonder if MelanieN and Jytdog would like to comment further. Your expertise is appreciated. Thanks, BatteryIncluded (talk) 06:44, 10 May 2014 (UTC)

Yes Drbogdan, I agree that "unnatural base pairs" (UBPs) is the best name for it because it is how the researchers call them and it will be referred to as such in future publications. It also side-steps the word "synthetic" that is loaded with different meanings depending on the perspective. Finally, not all existing synthetic nucleotides can forge links to form base pairs in DNA, but the UBPs do. So, In which article would you merge it to? (e.g create the UBPs subsection). I think that Expanded genetic code is bang on. What say you? We can always write a small section in related articles and have them all linked to the "main article" subsection. Cheers, BatteryIncluded (talk) 16:47, 10 May 2014 (UTC)

FWIW - I'm flexible with this atm - yes, the Expanded genetic code article seems relevant of course - but perhaps the Base pair article may also be a consideration - Enjoy! :) Drbogdan (talk) 16:34, 11 May 2014 (UTC)

Sorry, folks, I've been offline due to Real Life commitments. I think there are some great suggestions here, and I think one of the problems we need to deal with is that information on this topic is scattered among numerous article titles. Let's start by taking stock of all the articles we currently have about these man-made, not-found-in-nature nucleic acid compounds and components. I am aware of Synthetic DNA, Nucleic acid analogues, Artificial gene synthesis, Expanded genetic code - what else is there? I think all of these might better be combined into a single location, with redirects from all the obvious search terms. We could create a brand new article or merge all of these into a single article. I am open on which approach we take - the draft below for Unnatural base pairs is excellent - but I think we need to do some consolidation. Let's be lumpers rather than splitters.
In addition to the new or reformatted article about the unnatural/artificial/synthetic compounds that may function like genetic materials, I think there should also be a mention of current research at Base pairs and Nucleic acids. We could do that right away even before we decide on our overall approach to this kind of research. Again, though, I think we need a better section title than "Nucleic acids:Artificial nuclei acids analogs" - because to me as a chemist, these are not "analog(ue)s" of nucleic acids, they ARE nucleic acids; they are just not nucleic acids that occur in nature. --MelanieN (talk) 17:57, 11 May 2014 (UTC)

Hello. That sounds like a major project affecting multiple articles. Is there a Molecular Biology Project Team in Wikipedia? We should collaborate with them and check if such reorganization has been discussed before; we should assess the advantages and strategy with them. -BatteryIncluded (talk) 16:11, 12 May 2014 (UTC)

I was wondering if we can close the merger discussion now. Looks like reached a consensus in doing the merging, but the target article will be Expanded genetic code or Base pair. The text to merge is the draft below. Is everyone OK with this? Cheers, -BatteryIncluded (talk) 19:21, 13 May 2014 (UTC)

Draft

Please review my initial draft with a big red pen. Thanks, BatteryIncluded (talk) 15:34, 11 May 2014 (UTC)

Unnatural base pair (UBP)

An unnatural base pair is a designed subunit (or nucleobase) of DNA which is created in a laboratory and does not occur in nature. DNA sequences have been described which use newly created nucleobase to form a third base pair, in addition to the two base pairs naturally found in living organism, adenine–thymine (A-T) and cytosine–guanine (C-G).

In 1989 Steven Benner, then at the Swiss Federal Institute of Technology in Zurich, and his team led with modified forms of cytosine and guanine into DNA molecules in vitro. The nucleotides, which encoded RNA and proteins, were successfully replicated in vitro. Since then, Benner's team has been trying to engineer cells that can make foreign bases from scratch, obviating the need for a feedstock.

In 2012, a group of American scientists led by Floyd Romesberg, a chemical biologist at the Scripps Research Institute in San Diego, California, published that his team designed an unnatural base pair (UBP). The two new artificial nucleotides or Unnatural Base Pair (UBP) were named d5SICS and dNaM. More technically, these artificial nucleotides bearing hydrophobic nucleobases, feature two fused aromatic rings that form a (d5SICS–dNaM) complex or base pair in DNA. His team designed a variety of in vitro or "test tube" templates (I'm skipping technical molec bio term "Library") containing the unnatural base pair and they confirmed that it was efficiently replicated with high fidelity in virtually all sequence contexts using the modern standard in vitro techniques, namely PCR amplification of DNA and PCR-based applications. Their results show that for PCR and PCR-based applications, the d5SICS–dNaM unnatural base pair is functionally equivalent to a natural base pair, and when combined with the other two natural base pairs used by all organisms, A–T and G–C, they provide a fully functional and expanded six-letter "genetic alphabet".

In 2014 the same team from the Scripps Research Institute reported that they synthesized a stretch of circular DNA known as a plasmid containing natural T-A and C-G base pairs along with the best-performing UBP Romesberg's laboratory had designed, and inserted it into cells of the common bacterium E. coli that successfully replicated the unnatural base pairs through multiple generations. The transfection did not hamper the growth of the E. coli cells, and showed no sign of losing its unnatural base pairs to its natural DNA repair mechanisms. This is the first known example of a living organism passing along an expanded genetic code to subsequent generations. Romesberg said he and his colleagues created 300 variants to refine the design of nucleotides that would be stable enough and would be replicated as easily as the natural ones when the cells divide. This was in part achieved by the addition of a supportive algal gene that expresses a nucleotide triphosphate transporter which efficiently imports the triphosphates of both d5SICSTP and dNaMTP into E. coli bacteria. Then, the natural bacterial replication pathways use them to accurately replicate a plasmid containing d5SICS–dNaM. Other researchers were surprised that the bacteria replicated these human-made DNA subunits.

The successful incorporation of a third base pair is a significant breakthrough toward the goal of greatly expanding the number of amino acids which can be encoded by DNA, from the existing 20 amino acids to a theoretically possible 172, thereby expanding the potential for living organisms to produce novel proteins. The artificial strings of DNA do not encode for anything yet, but scientists speculate they could be designed to manufacture new proteins which could have industrial or pharmaceutical uses. Experts said the synthetic DNA incorporating the unnatural base pair raises the possibility of life forms based on a different DNA code.

Refs

Comments on draft

Seems *Excellent* to me at the moment - this could be part of a newly created future article I would think - esp if the study is verified by other researchers - and/or if new different UBP pairs are reported - thanks for the effort - it's *greatly* appreciated - Enjoy! :) Drbogdan (talk) 15:48, 11 May 2014 (UTC)

Great improvements on the existing article, bringing in more science and toning down the speculation. But I would suggest our article not start with the Romesberg group's research, as if it came out of nowhere. Romeseberg himself gives precedence to the Benner group with their modified forms of C and G - which although not entirely new creations are still unnatural nucleobases. More comments later, still pretty busy offline. --MelanieN (talk) 18:04, 11 May 2014 (UTC)
P.S. I took the liberty of copyediting your draft in minor ways; no changes to meaning. --MelanieN (talk) 18:09, 11 May 2014 (UTC)

Good point. Please give it a go in the next couple of days. I am not familiar with the chronology and the teams. Thanks. --BatteryIncluded (talk) 23:24, 11 May 2014 (UTC)

I have the full Nature paper now. It has a diagram of the chemical structure of the d5SICS–dNaM UBP. It would be nice to add it to Wikimedia Commons but I don't know how to comply with the copyrights. Any help will be appreciated. BatteryIncluded (talk) 16:53, 12 May 2014 (UTC)

Yes, I agree - relevant images from the Nature article would be nice - I considered this earlier - however, copyright may be an issue afaik atm - I also agree - any help from others with this would be appreciated - Enjoy! :) Drbogdan (talk) 17:30, 13 May 2014 (UTC)

The discussion above is closed. Please do not modify it. Subsequent comments should be made on the appropriate discussion page. No further edits should be made to this discussion.