Talk:Expanded genetic code

A fact from Expanded genetic code appeared on Wikipedia's Main Page in the Did you know column on 24 October 2009. The text of the entry was as follows:

Did you know... that several groups have managed to add non-natural bases to DNA, while others have added non-natural amino acids into the genetic code?

A record of the entry may be seen at Wikipedia:Did you know archive/2009/October.

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Untitled

I have copied part of this into genetic code so this atm is repeated. but I will expand on it soon. so plz do not delete. --Squidonius (talk) 21:14, 13 October 2009 (UTC)[reply]

expanded (forgot to log in though)--Squidonius (talk) 12:50, 16 October 2009 (UTC)[reply]

Removed for lack of clarity

Removed "from the existing 20 to a theoretically possible 172," because it is not clear what the 20 refers to (though it probably means the 20 amino acids expressed by the standard code) or where the theoretically possible 172 comes from. If the same redundancy as the current codes were used an expansion of about a factor of four might be expected, for example. It is probable that the 172 is based on expanding the existing 64 codes to 216 giving an additional 152 codes, which if they were mapped uniquely to new AAs would yield a total of 172 AAs. It is not clear, however, with the massive re-engineering of the transcription machinery required, why the redundancy in the existing code need be preserved, nor indeed the coding length of 3. All the best: Rich Farmbrough, 01:31, 28 August 2014 (UTC).

Query

First, a thanks. I created this page over five years ago, but I haven't touched it since. I am glad it is in a good shape and bold edits are contested. Today, I was hoping to give it focus and update it with recent literature (in procrastination from writing a grant), but got stopped midway. I promise I'll do it soon. I was partially surprised that my edit got reverted. In it's current form it has a repetition (there are 20 amino acids) and lacks a summary of the how it is done conceptually and what the articles covers, so I will fix it. I will add reference, but I was hoping to build on my previous edit. I assume it wasn't a needs references issue, right? Two issues I see that are problematic are (i) choice of the usage of terms standard and nonstandard, and (ii) the claim that UAG recoding is the most prominent. --Squidonius (talk) 05:12, 2 February 2015 (UTC)[reply]

lead

Squidonius please stop adding content to the lead that is not in the body. please see WP:LEAD. Please improve the body first, and if what you add is important enough to add to the lead, then do it afterwards, after reviewing the whole article. thanks. Jytdog (talk) 00:17, 3 February 2015 (UTC)[reply]

Thank you for your concerns. I was planning on editing the body accordingly —I was just starting from the top as one does.

The article needs structure (hence the lead), focus and a more rounded coverage: at its current state it has as much focus as an undergraduate essay —I'll admit I am partly to be blamed (it is a partial transplant of a lit review).

Parenthetically, I would like to stress that I know what I am doing: I haven't been active for a long while on wikipedia, but I am not a new user, in fact I have done many bold edits (e.g. I untangled the mess that used to E. coli and split it into three articles) and, in real life, I have authored several peer-reviewed papers, so I know how to make a story coherent.

Therefore, in conclusion, I would like to know if you are okay with my editing this article and would really appreciate any suggestion or help.

really, please actually read WP:LEAD. it is not logical to start with the lead. The lead should be the last thing you do if you want to update an article. The lead just summarizes the body, and you cannot summarize something from the body if it isn't there yet. Right? And weight in the lead, should reflect weight in the body. And you cannot know the weight something has in the body if it isn't there yet, either. Jytdog (talk) 02:42, 3 February 2015 (UTC)[reply]

but of course!!! please be bold. please also use secondary sources, not primary ones. WP is not a scientific review article. Thanks! Jytdog (talk) 02:43, 3 February 2015 (UTC)[reply]

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mouse code

In this section

Orthogonal sets in mammalian cells

   tRNATyr-TyrRS pair from Bacillus stearothermophilus[41]
   modified tRNATrp-TrpRS pair from Bacillus subtilis trp[42]
   tRNALeu–LeuRS pair from Escherichia coli[43]
   tRNAAmber-PylRS pair from the archaeon Methanosarcina barkeri and Methanosarcina mazei

41, 42 and 43 are primary sources. The last one is unsourced. I added an important primary source. @Jytdog: reverted it. I am going to insert it again. I was thanked by one experienced user for the original edit. I would like to hear comments fom the community about this brewing edit conflict. @Adrian J. Hunter: Thanks, DennisPietras (talk) 16:04, 24 February 2017 (UTC)[reply]

It is great that you want to improve the article. Rather than arguing in favor of a low quality edit by pointing out the results of other low quality edits, why not improve the article by adding better refs? The specific issue as I noted in my edit notes was WP:NOTNEWS and the primary source. Adding content about hot off the presses science is unwise in an encyclopedia; we have no deadline here, and papers are sometimes retracted and often just ignored. As an example, remember that scientist who published work showing that if you shake cells (really!) you could turn them into stem cells? There was huge media hype around that. And yep, people rushed to add content based on the hyped primary source to WP. (Note the edit date, and the date the paper came out) only to delete it later when the paper was retracted. (We actually have a whole article on that mess Stimulus-triggered acquisition of pluripotency) We should not be jerking the public around like that. There is no reason to do that - we have no deadline here. Jytdog (talk) 16:08, 24 February 2017 (UTC)[reply]

@Jytdog: et al. I am going to wait for other comments about this debate before I act further. However, to make it easier for people to see the text in question, here it is...

In 2017 a mouse engineered with an extended genetic code that can produce proteins with unnatural amino acids was reported.^[1] DennisPietras (talk) 02:21, 26 February 2017 (UTC)[reply]

Sorry to keep you waiting, DennisPietras.

I don't see any material difference between the line DennisPietras added and the other content in nearby sections, so I don't see any point discussing that edit specifically – either we want everything in those sections (including DennisPietras' addition), or we want to get rid of the entire sections. Here are the sections I'm referring to:

Extended content

Orthogonal sets in E. coli

The orthogonal pairs of synthetase and tRNA that work for one organism may not work for another, as the synthetase may mis-aminoacylate endogenous tRNAs or the tRNA be mis-aminoacylated itself by an endogenous synthetase. As a result, the sets created to date differ between organisms.

tRNA^Tyr-TyrRS pair from the archaeon Methanococcus jannaschii
tRNA^Lys–LysRS pair from the archaeon Pyrococcus horikoshii^[2]
tRNA^Glu–GluRS pair from Methanosarcina mazei^[3]
leucyl-tRNA synthetase from Methanobacterium thermoautotrophicum and a mutant leucyl tRNA derived from Halobacterium sp^[4]
tRNA^Amber-PylRS pair from the archaeon Methanosarcina barkeri and Methanosarcina mazei
tRNA^Amber-3-Iodotyrosyl-tRNA synthetase (variant of aminoacyl-tRNA synthetase from Methanocaldococcus jannaschii)^[5]

Orthogonal sets in yeast

tRNA^Tyr-TyrRS pair from Escherichia coli^[6]
tRNA^Leu–LeuRS pair from Escherichia coli^[7]
tRNA^iMet from human and GlnRS from Escherichia coli^[8]
tRNA^Amber-PylRS pair from the archaeon Methanosarcina barkeri and Methanosarcina mazei^[9]
tRNA^Amber-4,5-dimethoxy-2-nitrobenzyl-cysteinyl-tRNA synthetase^[10]

Orthogonal sets in mammalian cells

tRNA^Tyr-TyrRS pair from Bacillus stearothermophilus^[11]
modified tRNA^Trp-TrpRS pair from Bacillus subtilis trp^[12]
tRNA^Leu–LeuRS pair from Escherichia coli^[13]
tRNA^Amber-PylRS pair from the archaeon Methanosarcina barkeri and Methanosarcina mazei
In 2017 a mouse engineered with an extended genetic code that can produce proteins with unnatural amino acids was reported.^[14]

References

^ Han, S.; et al. "Expanding the genetic code of Mus musculus". Nat. Commun. 8. doi:10.1038/ncomms14568. {{cite journal}}: Explicit use of et al. in: |last1= (help)
^ Anderson, J.C.; Wu, N.; Santoro, S.W.; Lakshman, V.; King, D.S.; Schultz, P.G. (2004). "An expanded genetic code with a functional quadruplet codon". Proc Natl Acad Sci USA. 101 (20): 7566–7571. Bibcode:2004PNAS..101.7566A. doi:10.1073/pnas.0401517101. PMC 419646. PMID 15138302.
^ Santoro, S.W.; Anderson, J.C.; Lakshman, V.; Schultz, P.G. (2003). "An archaebacteria-derived glutamyl-tRNA synthetase and tRNA pair for unnatural amino acid mutagenesis of proteins in Escherichia coli". Nucleic Acids Res. 31 (23): 6700–6709. doi:10.1093/nar/gkg903. PMC 290271. PMID 14627803.
^ Anderson, J.C.; Schultz, P.G. (2003). "Adaptation of an orthogonal archaeal leucyl-tRNA and synthetase pair for four-base, amber, and opal suppression". Biochemistry. 42 (32): 9598–9608. doi:10.1021/bi034550w. PMID 12911301.
^ Minaba, Masaomi; Kato, Yusuke (2013). "High-Yield, Zero-Leakage Expression System with a Translational Switch Using Site-Specific Unnatural Amino Acid Incorporation". Applied and Environmental Microbiology. 80 (5): 1718–1725. doi:10.1128/AEM.03417-13.
^ Chin, J.W.; Cropp, T.A.; Anderson, J.C.; Mukherji, M.; Zhang, Z.; Schultz, P.G. (2003). "An expanded eukaryotic genetic code". Science. 301 (5635): 964–967. Bibcode:2003Sci...301..964C. doi:10.1126/science.1084772. PMID 12920298.
^ Wu, N.; Deiters, A.; Cropp, T.A.; King, D.; Schultz, P.G. (2004). "A genetically encoded photocaged amino Acid". J Am Chem Soc. 126 (44): 14306–14307. doi:10.1021/ja040175z. PMID 15521721.
^ Kowal, A.K.; Kohrer, C.; RajBhandary, U.L. (2001). "Twenty-first aminoacyl-tRNA synthetase–suppressor tRNA pairs for possible use in site-specific incorporation of amino acid analogues into proteins in eukaryotes and in eubacteria". Proc Natl Acad Sci USA. 98 (5): 2268–2273. Bibcode:2001PNAS...98.2268K. doi:10.1073/pnas.031488298. PMC 30127. PMID 11226228.
^ Hancock, S. M.; Uprety, R; Deiters, A; Chin, J. W. (2010). "Expanding the genetic code of yeast for incorporation of diverse unnatural amino acids via a pyrrolysyl-tRNA synthetase/tRNA pair". Journal of the American Chemical Society. 132 (42): 14819–24. doi:10.1021/ja104609m. PMC 2956376. PMID 20925334.
^ Kang, Ji-Yong (2013). "In vivo Expression of a Light-activatable Potassium Channel Using Unnatural Amino Acids". Neuron. 80: 358–370. doi:10.1016/j.neuron.2013.08.016.
^ Sakamoto, K.; Hayashi, A.; Sakamoto, A.; Kiga, D.; Nakayama, H.; Soma, A.; Kobayashi, T.; Kitabatake, M.; et al. (2002). "Site-specific incorporation of an unnatural amino acid into proteins in mammalian cells". Nucleic Acids Res. 30 (21): 4692–4699. doi:10.1093/nar/gkf589. PMC 135798. PMID 12409460. {{cite journal}}: Explicit use of et al. in: |first9= (help)
^ Zhang, Z.; Alfonta, L.; Tian, F.; Bursulaya, B.; Uryu, S.; King, D.S.; Schultz, P.G. (2004). "Selective incorporation of 5-hydroxytryptophan into proteins in mammalian cells". Proc. Natl. Acad. Sci. USA. 101 (24): 8882–8887. Bibcode:2004PNAS..101.8882Z. doi:10.1073/pnas.0307029101. PMC 428441. PMID 15187228.
^ Wang, W.; Takimoto, J.; Louie, G.V.; Baiga, T.J.; Noel, J.P.; Lee, K.F.; Slesinger, P.A.; Wang, L. (2007). "Genetically encoding unnatural amino acids for cellular and neuronal studies". Nat. Neurosci. 10 (8): 1063–1072. doi:10.1038/nn1932. PMC 2692200. PMID 17603477.
^ Han, S.; et al. "Expanding the genetic code of Mus musculus". Nat. Commun. 8. doi:10.1038/ncomms14568. {{cite journal}}: Explicit use of et al. in: |last1= (help)

Rarely do I find myself in disagreement with Jytdog, whose work in purging dreck from Wikipedia I respect tremendously, but I'm not seeing any problem with this section. I don't think the intention behind WP:NOTNEWS is to prevent primary sources being used until some amount of time has passed; that part of policy even says "editors are encouraged to include current and up-to-date information within [Wikipedia's] coverage." Rather, I think the salient policy is WP:PRIMARY. Said policy explicitly permits the use of primary sources with care, subject to several caveats, none of which I can see apply here. Use of primary sources to support individual lines in list-content is common in featured lists such as List of ant subfamilies, List of Armillaria species, and List of parasites of the marsh rice rat.

Regarding the Stimulus-triggered acquisition of pluripotency saga, I think it's problematic to let a single extraordinary event strongly influence the way we do day-to-day editing – hard cases make bad law. In any case, a reliance on secondary sources would not have kept all that out of Wikipedia, as the original Nature paper was rapidly (and with disappointing credulity) reported on by numerous reputable secondary sources, eg New Scientist, BBC, The Guardian. Adrian J. Hunter^{(talk•contribs)} 11:57, 1 March 2017 (UTC)[reply]

Thanks for your note. The shaken-cell story is just an example I use and of course it is hyperbolic. :) However a) the replication crisis is a very real thing, and b) our mission is to provide the public with accepted knowledge and not with breaking news in science or elsewhere, and c) there is WP:NODEADLINE here and not a darn thing that is bad about waiting to see discussion of the mouse work by people independent of the work, in a review.

With regard to the excerpted section, assembling sections based on primary sources, like the excerpted section, inevitably leads to a) WP:OR - the actual construction of a history here in WP instead of summarizing the history told elsewhere, and b) WP:NPOV problems with WEIGHT. I have intended for a while to go over the excepted section and rework it based on secondary sources, and have not gotten to that yet.

All that said, I bow to consensus and if others want to keep the paper about the mouse, that is what will happen. Of course. Now two editors want to keep. Let's give it a couple of days to see if anybody else wants to pitch in. If not, I will not object to restoration. Jytdog (talk) 18:45, 1 March 2017 (UTC)[reply]

@Jytdog: I am ecstatic to read that you are open to the possibility of including this, and my THANKS to Adrian J. Hunter for commenting in a much better way than I can. Let me assure you again that since our intitial disagreement about cffDNA, I have seen at least a dozen papers that I initially wanted to include in wp articles, but backed off of because of the stricter policy of wp on med articles. Our interests may still overlap at times, becaue as I was rating about 2K unassessed gentics articles, I found lots that were residing in both the medicine and genetics projects, and it may be difficult to draw the line between bassic biology and medicine, but I will try to tread gently, even with the enormous weight on the thin wheels of my chair!

DennisPietras (talk) 19:09, 1 March 2017 (UTC)[reply]

I am glad you thought twice; that is what you should do. I am not sure Adrian was aware of your adamancy about including breaking science news in WP. NOTNEWS is policy everywhere, and the call to use secondary, not primary, sources, is deep in the guts of WP, as I have already wasted too much time trying to explain to you. You continue to try to turn WP articles into literature review articles themselves and this is not what WP is. Many scientists who come here struggle with the genre issue and you are being more resistant to learning than most. Jytdog (talk) 19:20, 1 March 2017 (UTC)[reply]

The replication crisis is a dire and underappreciated issue in research, and if these sections listed primary papers that purported to show nutrients that caused or prevented cancer, I'd advocate an immediate purge. But I see the papers under discussion as listing relatively mundane and uncontroversial technical progressions; I don't see them as the sorts of things that need to be replicated or otherwise confirmed before I believe them. I actually don't see a problem with Wikipedians assembling quasi-histories by listing primary sources, so long as novel WP:SYNTHesis is avoided and excessive WP:WEIGHT is not put on any particular primary source. I guess the proper use of primary sources is always going to be a difficult area about which competent Wikipedians can disagree. It might be that my long time editing here and my slow edit rate have left my intuitions lagging behind current best practice. Anyway, I certainly wouldn't object to re-working these sections based on a good review article or book or whatever. Adrian J. Hunter^{(talk•contribs)} 23:50, 1 March 2017 (UTC)[reply]

We are getting into NOTFORUM territory but there is no part of the scientific enterprise in the field of biology that is free of the replication crisis - the issues that drive it (intense competition for grants, poor peer review, and acceptance of low Ns and other bad practices at journals) are the same across the board. And yeah, editing based on high sourcing standards is almost always welcome and acceptable by all - it is only editing with poor sources that leads to time-wasting theoretical discussions like this.

and no, and hell no. Assembling a history in WP is the definition of WP:OR. It is not what we do here. That is fundamental and basic WP 101 stuff. Jytdog (talk) 00:07, 2 March 2017 (UTC)[reply]

@Jytdog and Adrian J. Hunter: It has been more than a week with no other discussion, so I am going to add the section back into the article. Thanks, DennisPietras (talk) 19:22, 10 March 2017 (UTC)[reply]

that would be an odd thing to do. Jytdog (talk) 19:51, 10 March 2017 (UTC)[reply]

Odd? You wrote above "All that said, I bow to consensus and if others want to keep the paper about the mouse, that is what will happen." Do you realize how odd it is that you contradict yourself and cite wp policies that contract your "jytdog policy" as if they support you? I appreciate and admire your efforts to eliminate COI's from wp, but I think you really should take a dispassionate look at your actions about primary sources and see how out of line they are with current community standards, IMHO. You reviewed 500 of my recent edits. Don't you realize that other experienced editors aren't bothered by my edits? It seems to me that you may be attached to strong opinions you previously formed about primary sources.Detaching from them might be helpful for you, me and wp in general, so that we can spend time improving the content. I'm not citing alternate facts. I'm updating articles. Thanks, DennisPietras (talk) 03:23, 11 March 2017 (UTC)[reply]

You want it; Adrian is kind of meh, I say no. There is no consensus. Jytdog (talk) 17:26, 11 March 2017 (UTC)[reply]

@Jytdog: "Adrian is kind of meh"? The reason I alerted him to this discussion is that he thanked me for the addition before you reverted it! I really worry that you are having trouble dealing with the reality of how unusual you are in your stance against primary sources, and I am getting tired of dealing with your harrassment of my edits in particular, while ignoring other primary sources right next to mine. Revert some more, and we'll end up in arbitration and see if someone else can block some sense into you. DennisPietras (talk) 02:14, 13 March 2017 (UTC)[reply]

To clarify, although I think it would be great if the section were re-worked based on secondary or tertiary sources, I still think the section is acceptable as-is. I think we need more voices to achieve consensus, so I've requested feedback at WT:GEN and WT:MCB. Adrian J. Hunter^{(talk•contribs)} 06:14, 13 March 2017 (UTC)[reply]

[1] Han, S.; et al. "Expanding the genetic code of Mus musculus". Nat. Commun. 8. doi:10.1038/ncomms14568. {{cite journal}}: Explicit use of et al. in: |last1= (help)

[2] Anderson, J.C.; Wu, N.; Santoro, S.W.; Lakshman, V.; King, D.S.; Schultz, P.G. (2004). "An expanded genetic code with a functional quadruplet codon". Proc Natl Acad Sci USA. 101 (20): 7566–7571. Bibcode:2004PNAS..101.7566A. doi:10.1073/pnas.0401517101. PMC 419646. PMID 15138302.

[3] Santoro, S.W.; Anderson, J.C.; Lakshman, V.; Schultz, P.G. (2003). "An archaebacteria-derived glutamyl-tRNA synthetase and tRNA pair for unnatural amino acid mutagenesis of proteins in Escherichia coli". Nucleic Acids Res. 31 (23): 6700–6709. doi:10.1093/nar/gkg903. PMC 290271. PMID 14627803.

[4] Anderson, J.C.; Schultz, P.G. (2003). "Adaptation of an orthogonal archaeal leucyl-tRNA and synthetase pair for four-base, amber, and opal suppression". Biochemistry. 42 (32): 9598–9608. doi:10.1021/bi034550w. PMID 12911301.

[5] Minaba, Masaomi; Kato, Yusuke (2013). "High-Yield, Zero-Leakage Expression System with a Translational Switch Using Site-Specific Unnatural Amino Acid Incorporation". Applied and Environmental Microbiology. 80 (5): 1718–1725. doi:10.1128/AEM.03417-13.

[6] Chin, J.W.; Cropp, T.A.; Anderson, J.C.; Mukherji, M.; Zhang, Z.; Schultz, P.G. (2003). "An expanded eukaryotic genetic code". Science. 301 (5635): 964–967. Bibcode:2003Sci...301..964C. doi:10.1126/science.1084772. PMID 12920298.

[7] Wu, N.; Deiters, A.; Cropp, T.A.; King, D.; Schultz, P.G. (2004). "A genetically encoded photocaged amino Acid". J Am Chem Soc. 126 (44): 14306–14307. doi:10.1021/ja040175z. PMID 15521721.

[8] Kowal, A.K.; Kohrer, C.; RajBhandary, U.L. (2001). "Twenty-first aminoacyl-tRNA synthetase–suppressor tRNA pairs for possible use in site-specific incorporation of amino acid analogues into proteins in eukaryotes and in eubacteria". Proc Natl Acad Sci USA. 98 (5): 2268–2273. Bibcode:2001PNAS...98.2268K. doi:10.1073/pnas.031488298. PMC 30127. PMID 11226228.

[9] Hancock, S. M.; Uprety, R; Deiters, A; Chin, J. W. (2010). "Expanding the genetic code of yeast for incorporation of diverse unnatural amino acids via a pyrrolysyl-tRNA synthetase/tRNA pair". Journal of the American Chemical Society. 132 (42): 14819–24. doi:10.1021/ja104609m. PMC 2956376. PMID 20925334.

[10] Kang, Ji-Yong (2013). "In vivo Expression of a Light-activatable Potassium Channel Using Unnatural Amino Acids". Neuron. 80: 358–370. doi:10.1016/j.neuron.2013.08.016.

[11] Sakamoto, K.; Hayashi, A.; Sakamoto, A.; Kiga, D.; Nakayama, H.; Soma, A.; Kobayashi, T.; Kitabatake, M.; et al. (2002). "Site-specific incorporation of an unnatural amino acid into proteins in mammalian cells". Nucleic Acids Res. 30 (21): 4692–4699. doi:10.1093/nar/gkf589. PMC 135798. PMID 12409460. {{cite journal}}: Explicit use of et al. in: |first9= (help)

[12] Zhang, Z.; Alfonta, L.; Tian, F.; Bursulaya, B.; Uryu, S.; King, D.S.; Schultz, P.G. (2004). "Selective incorporation of 5-hydroxytryptophan into proteins in mammalian cells". Proc. Natl. Acad. Sci. USA. 101 (24): 8882–8887. Bibcode:2004PNAS..101.8882Z. doi:10.1073/pnas.0307029101. PMC 428441. PMID 15187228.

[13] Wang, W.; Takimoto, J.; Louie, G.V.; Baiga, T.J.; Noel, J.P.; Lee, K.F.; Slesinger, P.A.; Wang, L. (2007). "Genetically encoding unnatural amino acids for cellular and neuronal studies". Nat. Neurosci. 10 (8): 1063–1072. doi:10.1038/nn1932. PMC 2692200. PMID 17603477.

[14] Han, S.; et al. "Expanding the genetic code of Mus musculus". Nat. Commun. 8. doi:10.1038/ncomms14568. {{cite journal}}: Explicit use of et al. in: |last1= (help)

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