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Expanding The Genetic Code: The World’s First Truly Unnatural Organism
ScienceDaily Magazine ^ | 01/14/2003 | American Chemical Society

Posted on 01/14/2003 6:55:21 AM PST by forsnax5

From time immemorial, every living thing has shared the same basic set of building blocks -- 20 amino acids from which all proteins are made. That is, until now: A group of scientists say they have, for the first time, created an organism that can produce a 21st amino acid and incorporate it into proteins completely on its own. The research should help probe some of the central questions of evolutionary theory.

The findings are scheduled to appear in the Jan. 29 print edition of the Journal of the American Chemical Society, a peer-reviewed journal of the world's largest scientific society. The article was initially published Jan. 4 on the journal's Web site.

The project could eventually give concrete answers to questions that have generally been regarded as purely speculative: Is 20 the ideal number of basic building blocks? Would additional amino acids lead to organisms with enhanced function? Why has the genetic code not evolved further?

"Why did life settle on 20 amino acids?" asks Ryan Mehl, Ph.D., previously a researcher at the Scripps Research Institute in La Jolla, Calif., and now on the faculty of Franklin & Marshall College in Lancaster, Pa. "Would more amino acids give you a better organism -- one that could more effectively adapt if placed under selective pressure?"

To address this question, Mehl and a team of scientists led by Peter Schultz, Ph.D., professor of chemistry at Scripps, added a pathway to an E. coli bacterium that allows it to make a new amino acid -- p-aminophenylalanine (pAF) -- from simple carbon sources. Analytical techniques showed that pAF was incorporated into proteins with a fidelity rivaling that of the 20 natural amino acids.

"This allows you to have a totally autonomous organism that you can 'race'in one pot by evolving the new bacterium alongside its ancestors with 20 amino acids," says Christopher Anderson, a researcher at Scripps and another author of the paper. By racing the organisms -- exposing both to selective pressures at the same time and watching their development -- the researchers hope to see if the organism with the expanded genetic code has an evolutionary advantage over natural organisms.

A number of scientists have previously added unnatural amino acids to organisms, but most of these experiments involved eliminating the organism's supply of the natural amino acid and substituting a close relative. "So, in the end, you still have a 20 amino acid bacterium, but it's using an unnatural amino acid instead of the natural one," Anderson says.

"What our group really wanted to do is expand the genetic code, not just recode it. To do that, it takes a lot more effort. You have to come up with some way of specifically denoting how the protein is going to encode this 21st amino acid, because everything else in the genetic code already has a meaning associated with it."

To solve the problem, they used a process called amber suppression. This requires taking a stop codon -- a chunk of the genetic code that acts as a roadblock for protein synthesis -- and making it no longer mean "stop." Instead it now codes for the unnatural amino acid, so that the only way to suppress the codon is with the proper unnatural amino acid. "So you basically have a whole new pathway that you've created where the unnatural amino acid gets specifically [placed] onto a t-RNA," Anderson says.

The true novelty of the current paper is in biosynthesis -- the ability of the bacterium to make the new amino acid by itself, as opposed to being fed an unnatural amino acid from an outside source. "This bug is self-sufficient; it can make, load and incorporate the new amino acid in the emerging protein all on its own," Mehl says. "It's a bona fide unnatural organism now. Essentially, this bacterium can be added to a minimal media (salts and a basic carbon source) and it's able to do the rest."

E. coli is notorious for its ability to quickly reproduce, which could conjure images of mutant bacteria running wild. "We crippled the organism's ability to biosynthesize leucine [one of the 20 essential amino acids] to avoid any risk that the organism could propagate outside a controlled lab setting," Anderson says. "Our unnatural organism will always live in the lab. We have no intention of putting it out in the wild or in commercial products where it could 'get out.'"

How this organism behaves in future experiments will determine, in part, where the research goes from here. "We are now focusing on more 'useful' unnatural amino acids such as ketone- and PEG-containing amino acids," Anderson says. PEG stands for polyethylene glycol, a polymer that can be connected to proteins used in medicines to enhance their therapeutic value. "I don't think it is at all unrealistic to imagine that in the not-too-distant future there will be a transgenic goat that can biosynthesize a PEG amino acid and incorporate it into therapeutic proteins secreted into the animal's milk," Anderson says. "We are just beginning to look at the applications, but we have many projects in the works."


TOPICS: News/Current Events
KEYWORDS: biology; crevolist; evolution; genetics
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Pushing the genetic code in new directions...
1 posted on 01/14/2003 6:55:21 AM PST by forsnax5
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To: *crevo_list; VadeRetro; PatrickHenry; jennyp; balrog666; general_re; Right Wing Professor; ...
Evil geneticists add new protein to helpless microbe! Film at Eleven!
2 posted on 01/14/2003 7:02:42 AM PST by forsnax5
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To: forsnax5
Marking for later reading..
3 posted on 01/14/2003 7:05:56 AM PST by AntiGuv (™)
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To: VadeRetro; jennyp; Junior; longshadow; *crevo_list; RadioAstronomer; Scully; Piltdown_Woman; ...
Mmrruuuhahahahahah!

[This ping list for the evolution -- not creationism -- side of evolution threads, and sometimes for other science topics. To be added (or dropped), let me know via freepmail.]

4 posted on 01/14/2003 7:11:43 AM PST by PatrickHenry (PH is really a great guy! Why don't the creos understand him?)
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To: forsnax5
Proof of intelligent design!!!1!

It's no such thing, actually. I just wanted to be the first of many to float this canard.

5 posted on 01/14/2003 7:17:29 AM PST by Physicist
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To: forsnax5
>Expanding The Genetic Code: The World’s First Truly Unnatural Organism

Sooner or later,
everyone will have to learn
what rishathra means...

6 posted on 01/14/2003 7:20:29 AM PST by theFIRMbss
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To: forsnax5
Incorporation of unnatural amino acids is nothing new.

The article does says so, despite its misleading sensationalist title:

The true novelty of the current paper is in biosynthesis -- the ability of the bacterium to make the new amino acid by itself, as opposed to being fed an unnatural amino acid from an outside source.

The questions asked at the beginning are the stuff asked 40 years at the RNA Tie club and the like.

James Watson has a new book out. I'm sure there are other books that go over those times and the ideas.

7 posted on 01/14/2003 7:21:22 AM PST by tallhappy
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To: forsnax5
E. coli is notorious for its ability to quickly reproduce, which could conjure images of mutant bacteria running wild. "We crippled the organism's ability to biosynthesize leucine [one of the 20 essential amino acids] to avoid any risk that the organism could propagate outside a controlled lab setting," Anderson says. "Our unnatural organism will always live in the lab. We have no intention of putting it out in the wild or in commercial products where it could 'get out.'"

LOL... apparently they missed the central theme of Jurassic Park.

8 posted on 01/14/2003 7:23:18 AM PST by Teacher317
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To: forsnax5
"Why did life settle on 20 amino acids?" asks Ryan Mehl, Ph.D., previously a researcher at the Scripps Research Institute in La Jolla, Calif., and now on the faculty of Franklin & Marshall College in Lancaster, Pa. "Would more amino acids give you a better organism -- one that could more effectively adapt if placed under selective pressure?"

No, it'll just give you a Cadillac with those stuck-on gold carriage lights.

Simply having another amino acid available doesn't mean that it will be used unless a particular pre-existing gene codes for its use in a protein. The two ways a pre-existing gene could code for its use are 1. a spontaneous point mutation (or several of them, depending on how different the codon is from those for the 20 standard AAs) results in the amino acid substitution in the pre-existing gene, 2. someone deliberately engineers the mutations into a specific gene. The significance of this still has to be seen in the context of standard molecular biological techniques in which amino acid substitutions, deletions, or insertions are cloned into existing genes all the time in order to elucidate the wild type function of the protein in question. The story above would sort of be like someone deciding to include some completely unrelated building materials along with those for a pre-fab house in the hope of seeing whether or how the contractor will incorporate them into pre-existing building plans that don't specify their use.
9 posted on 01/14/2003 7:24:56 AM PST by aruanan
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To: forsnax5

10 posted on 01/14/2003 7:25:53 AM PST by egarvue (Martin Sheen is not my president...)
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11 posted on 01/14/2003 7:26:39 AM PST by Mo1 (Join the DC Chapter at the Patriots Rally III on 1/18/03)
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To: tallhappy
Perhaps the article itself is more interesting to you.
12 posted on 01/14/2003 7:28:26 AM PST by general_re
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To: Physicist
Why would you say it is not intelligent design? That is, of course, exactly what it is.

Studies like this do not address those questions. They are engineering feats that eventually may be of large value.

Read the comments of Anderson in the last paragraph to see what the article is about in implications. I, for one, appreciate that they've done this.

13 posted on 01/14/2003 7:28:35 AM PST by tallhappy
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To: Teacher317
LOL... apparently they missed the central theme of Jurassic Park.

Uh, the central theme of the fictional Jurassic Park came from the reality of the leucine-less E coli bacteria used in molecular biological research.
14 posted on 01/14/2003 7:29:02 AM PST by aruanan
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To: Teacher317
Jurassic Park is make believe.
15 posted on 01/14/2003 7:30:03 AM PST by tallhappy
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To: general_re
Thanks for the link.
16 posted on 01/14/2003 7:31:58 AM PST by tallhappy
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To: tallhappy
My pleasure. Unfortunately, it'll have to be our (and a few others here, I expect) little secret, since I don't think that link is available to the general (subscription-less) public ;)
17 posted on 01/14/2003 7:34:32 AM PST by general_re
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To: tallhappy
Jurassic Park is make believe.

With a clear message, too... kind of like Aesop's Fables.

18 posted on 01/14/2003 7:40:01 AM PST by Oberon
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To: forsnax5
YEC read later
19 posted on 01/14/2003 7:47:58 AM PST by LiteKeeper
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To: tallhappy
Jurassic Park is make believe.

Suuuuure it is.

HA! You probably think that the moon landing was real!

/sarcastic humor>

20 posted on 01/14/2003 7:48:26 AM PST by Teacher317
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