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DNA with Three Base Pairs—A Step Towards Expanding the Genetic Code
Scripps Research Institute ^ | 2005-03-21 | Jason Socrates Bardi

Posted on 04/26/2005 7:26:08 PM PDT by dread78645

Scientists at The Scripps Research Institute in La Jolla, California are reporting at the 229th national meeting of the American Chemical Society progress toward the creation of a system for replicating a modified form of DNA containing an unnatural base pair.

According to the Scripps Research scientists, this finding is a significant step towards expanding the genetic code and the ability of DNA to act as an information storage and retrieval system in the test tube and in simple, engineered organisms, such as yeast or bacteria. DNA with three or more base pairs could find broad applications in a number of fields, including biotechnology, medicine, data storage, and security.

Instead of just the canonical base pairs "G-C" or guanine-cytosine, and "A-T" or adenine-thymine, the Scripps Research scientists' DNA has a third pairing: "3FB-3FB" between two unnatural bases called 3-fluorobenzene (or 3FB). Unlike other unnatural base pairs, DNA polymerases are able to replicate this base pair, albeit with reduced fidelity. To improve replication, the scientists also reported the development of a system capable of evolving polymerases to better recognize 3FB in DNA. Using a selection system some liken to evolution in the test tube, they are creating their own polymerase enzyme able to replicate the unnatural DNA.

While the polymerase does not replicate the unnatural DNA with the same fidelity observed in nature, (roughly one mistake for every 10 million bases of DNA copied), its fidelity is reasonable (typically making only one mistake for every 1000 base pairs). This is the first time anyone has been able to replicate unnatural DNA with fidelity against every possible mispair.

"We definitely are still working on improvements, especially in fidelity," says Scripps Research Assistant Professor Floyd Romesberg, who led the research. "Nevertheless, we are now able to replicate unnatural DNA."

The American Chemical Society, the world’s largest scientific society, is holding its national meeting in San Diego, CA, from March 13 to 17. The talk on this research, entitled "Efforts to Expand the Genetic Code," will be presented at 3:15 PM, Monday, March 14 during the Biomimetic Polymers symposium (POLY 193) at the San Diego Marriott in the Manchester rooms 1-2.


TOPICS: Culture/Society; Philosophy
KEYWORDS: crevolist; dna
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Interesting month old announcement
1 posted on 04/26/2005 7:26:15 PM PDT by dread78645
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To: PatrickHenry

ping.


2 posted on 04/26/2005 7:29:19 PM PDT by dread78645 (Sarcasm tags are for wusses.)
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To: dread78645

The future is here

3 posted on 04/26/2005 7:42:38 PM PDT by Popman (The American Left: Goose Stepping into the Future)
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To: dread78645

They really should think about getting a couple space colonies going before they get too 'creative' with this genetic roulette.


4 posted on 04/26/2005 7:45:55 PM PDT by Born to Conserve
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To: dread78645

Of computational interest, certainly. But it doesn't express to anything; i.e. it doesn't help code for an amino acid and hence doesn't make a protein.


5 posted on 04/26/2005 7:46:18 PM PDT by Billthedrill
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To: dread78645
The standard cellular model has segments of DNA transcribed into messenger RNA with a template for some specific protein. A ribosome latches onto the mRNA and exposes a 3 codon section. An amino acid bound to a transfer RNA (tRNA) with the matching conjugate to the exposed codon is bound and the amino acid is attached to the growing peptide. The ribosome ratchets down 3 more for the next item until it runs out.

Expanding the codon set to a new base pair will necessitate creation of a new set of amino acid-like substances that are bound to the appropriate conjugate tRNA. That will require some more magic in the lab. It will also take new enzyme to generate the mRNA strand to match the new 3FB codon.

Even after 30 years away from molecular biology, it really hasn't changed much. My challenge today was to stomp a digital signal processing algorithm down to size to run on an embedded processor. DNA or silicon...just a different way to write software and execute it.

6 posted on 04/26/2005 7:59:58 PM PDT by Myrddin
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To: dread78645

Very interesting. Rather esoteric, but certainly worth a ping.


7 posted on 04/27/2005 4:05:32 AM PDT by PatrickHenry (<-- Click on my name. The List-O-Links for evolution threads is at my freeper homepage.)
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To: VadeRetro; Junior; longshadow; RadioAstronomer; Doctor Stochastic; js1138; Shryke; RightWhale; ...
EvolutionPing
A pro-evolution science list with over 260 names.
See the list's description at my freeper homepage.
Then FReepmail to be added or dropped.

8 posted on 04/27/2005 4:06:59 AM PDT by PatrickHenry (<-- Click on my name. The List-O-Links for evolution threads is at my freeper homepage.)
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To: PatrickHenry
Note that this (pdf) file give some reasons for the optimality of four bases under evolutionary actions. If the link doesn't work, try searching for Yeong-Kong Huen.
9 posted on 04/27/2005 6:25:25 AM PDT by Doctor Stochastic (Vegetabilisch = chaotisch is der Charakter der Modernen. - Friedrich Schlegel)
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To: Doctor Stochastic
Note that this (pdf) file give some reasons for the optimality of four bases under evolutionary actions.

Thanks. The link works fine, and the article is fascinating. Now I've learned a new word: "4-narity." I think the abstract is certainly worth copying into the thread:

As a mathematician, the author is quite puzzled as to why textbooks and published papers in genetics, biochemistry and molecular biology are so glaringly silent on the important issue of how DNAs in modern time could have inherited uniquely four types of nucleotide bases. Is this an unwritten dogma in genetics? These put him on a hunting trail. The author hypothesizes that if in the prebiotic world there were only five types of bases, viz., adenine (A),cytosine (C),guanine (G), thymine (T) and uracil (U) and if it can be proved that genomes with number of bases other than four cannot survive in bioevolution then the puzzle is solved. He discovers that there are two equally satisfactory proofs one involving chaos theory whilst the other is so simple that even high school students should have no difficulties understanding it. Adhering to the philosophy of Occam’s Razor [1], a simple theory is deemed more elegant to be presented in this paper. To carry out analysis, the author conjures up various prebiotic scenerios where combinations ranging from 2 to 5 types of nucleotides selected from a stable of G,C,A,T and U could exist. A theorem on the influence of narity values on compressibility of strings is proved. Findings from analysis prove conclusively that only 4-nary genomes could survive whilst the remaining combinations either cannot be realised because of odd-narities or these could have gone extinct early in bioevolution. As a windfall, the proof also implies the nonexistence of the hypothetical RNA or preRNA world since Life started right away with 2-nary DNAs which was subsequently taken over by 4-nary DNAs. Most probably genetic takeover by RNAs and proteins happened much later in evolutionary in order to increase complexity incrementally. Starting with DNAs instead of RNAs certainly made genetic takeover by RNAs and proteins later on much easier.

10 posted on 04/27/2005 6:56:28 AM PDT by PatrickHenry (<-- Click on my name. The List-O-Links for evolution threads is at my freeper homepage.)
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To: Born to Conserve
They really should think about getting a couple space colonies going before they get too 'creative' with this genetic roulette.

How do you know that this sort of research isn't a prerequisite for viable space colonies? Maybe this will allow for rad-hard genomes, or really long lifetimes, or thick, variably-insulating skins able to withstand a hard vacuum.

But more practically, genetic diversification is a much more reliable path to long-term survival than space colonies. The disaster you fear is pure speculation, but many natural catastrophies unquestionably lie in our future. What characteristics will allow our children (and the species upon which they rely) to survive them? We have no way of knowing. The best hope is that they have as broad a palette as possible.

11 posted on 04/27/2005 6:57:08 AM PDT by Physicist
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To: Physicist
The best hope is that they have as broad a palette as possible.

Genetic "purity" in an inevitably changing environment is probably a guarantee of eventual extinction. Which demonstrates that you-know-who wasn't much of a Darwinist after all.

12 posted on 04/27/2005 7:11:22 AM PDT by PatrickHenry (<-- Click on my name. The List-O-Links for evolution threads is at my freeper homepage.)
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To: Physicist

In the interest of human survival I recommend insertion of a few cockroach genes. Perhaps "The Fly" guy was onto something.


13 posted on 04/27/2005 7:19:12 AM PDT by js1138 (e unum pluribus)
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To: dread78645

Interesting that even intelligent designers rely on evolution to solve problems of design.


14 posted on 04/27/2005 7:36:59 AM PDT by js1138 (e unum pluribus)
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To: PatrickHenry

Thanks for the ping!


15 posted on 04/27/2005 7:37:49 AM PDT by Alamo-Girl
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To: js1138

Yeah, but he tried the Lamarkian approach which doesn't allow one to squeeze much out of things.


16 posted on 04/27/2005 7:40:06 AM PDT by Doctor Stochastic (Vegetabilisch = chaotisch is der Charakter der Modernen. - Friedrich Schlegel)
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To: Doctor Stochastic

I don't consider anti-Lamarkianism to be an article of faith. Culture and language are Lamarkian, but evolve by selection. The source of variation is not critical to the working of evolution.


17 posted on 04/27/2005 7:44:19 AM PDT by js1138 (e unum pluribus)
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To: js1138

Yeah, but I just wanted to squeeze in the ending of the original movie, to give the press a head-up so to speak.


18 posted on 04/27/2005 7:53:52 AM PDT by Doctor Stochastic (Vegetabilisch = chaotisch is der Charakter der Modernen. - Friedrich Schlegel)
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To: Doctor Stochastic

There was a sequel? I missed it. Showing my age here.


19 posted on 04/27/2005 8:09:20 AM PDT by js1138 (e unum pluribus)
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To: js1138
In the interest of human survival I recommend insertion of a few cockroach genes.

I could make a comment here involving Democrats, Liberals or even Creationists, but I won't.
20 posted on 04/27/2005 9:50:19 AM PDT by Dimensio (http://angryflower.com/bobsqu.gif <-- required reading before you use your next apostrophe!)
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