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Enzymes stitch together non-natural DNA [Getting closer to lab-made life]
Nature Magazine ^ | 24 February 2004 | PHILIP BALL

Posted on 02/24/2004 3:55:22 AM PST by PatrickHenry

Guided evolution and HIV help create man-made stuff of life.

Researchers have found new ways to string together artificial DNA bases. The techniques could aid the creation of altered genetic material for applications in medicine and technology.

Floyd Romesberg and co-workers at the Scripps Research Institute in La Jolla, California, have harnessed the principles of evolution to find an enzyme capable of assembling non-standard DNA1.

In a second study, Steven Benner of the University of Florida in Gainesville and colleagues used an enzyme made by HIV, the virus that causes AIDS, to do the same job. Benner's enzyme is even capable of making multiple copies of non-natural DNA, opening up the possibility that the code could eventually evolve on its own2.

All natural DNA is made up of just four bases, but researchers have created non-natural bases. These can be used to make forms of DNA that are more robust than the natural kind and do not break apart when exposed to high temperatures. Such super-DNA could be useful in a wide range of medical and technological applications.

Stitched up

The tricky part is stitching these artificial bases into a chain, and getting the chains to replicate as natural DNA does. An enzyme called DNA polymerase does the job in nature.

DNA polymerase works its way along a template strand of DNA, reading each base and collecting a matching base to create a new, copied strand. But the enzyme turns up its nose at artificial bases.

By systematically tinkering with the structure of DNA polymerase at one or two specific locations, researchers can make enzymes that work with artificial bases. But this technique, called 'rational design', is a tedious and unpredictable process.

"Going the full distance is very difficult to do in a rational way," says Rui Sousa of the University of Texas Health Science Center at San Antonio. Sousa has designed polymerases that are being used commercially.

Romesberg and his co-workers tried a different approach called 'directed evolution'. They made millions of mutant polymerases by randomly scrambling part of the natural enzyme's chemical structure. Most of the mutants were useless, but some were quite good at stitching together non-standard bases. They plucked these useful mutants out of the crowd, and repeated the mutation and selection process to fine-tune their abilities.

After four rounds of selection, they found several mutants capable of doing the job. One was particularly good: it was able to copy the sequence of a template molecule into the modified form of DNA as efficiently and faithfully as DNA polymerase working with natural bases.

Carbon copies

But the mutant is not perfect. Like most modified polymerases, Romesberg's top candidate runs out of steam and stops working after adding five artificial bases to a growing chain.

Benner's team created a more successful polymerase by starting with a different enzyme altogether - a reverse transcriptase (RT) that is made by the HIV-1 form of the virus that causes AIDS. This RT mutates when the virus is hit with anti-HIV drugs. Benner's group checked mutated forms to find a modified RT capable of stitching two non-standard bases into strings of DNA. They fine-tuned this enzyme using rational design.

Their enzyme even works in a process called the polymerase chain reaction (PCR) , which is often used in biotechnology to make copies of short strands of DNA. Most constructed polymerases fail when researchers try to make multiple copies of artificial DNA using PCR; after several rounds of copying, imperfect polymerases start to weed out non-standard DNA. But Benner's enzyme does not seem to have this problem.


The four letters of life are being added to.


TOPICS: Culture/Society; Miscellaneous; Philosophy
KEYWORDS: crevolist; darwin; dna; enzymes; evolution
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Footnotes are at the original website. Bold font added by your humble poster.

This involves promising lab results, and practical benefits too. What are the anti-evos gonna do now?

1 posted on 02/24/2004 3:55:23 AM PST by PatrickHenry
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To: *crevo_list; VadeRetro; jennyp; Junior; longshadow; RadioAstronomer; Physicist; LogicWings; ...
PING. [This ping list is for the evolution side of evolution threads, and sometimes for other science topics. FReepmail me to be added or dropped.]
2 posted on 02/24/2004 3:56:24 AM PST by PatrickHenry
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To: Charles Henrickson

3 posted on 02/24/2004 4:08:20 AM PST by martin_fierro (I miss the Media Schadenfreude Ping)
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To: PatrickHenry
What are the anti-evos gonna do now?

Does it really matter what they say or do?
It's best to just ignore them.

They've been left behind.

4 posted on 02/24/2004 4:15:28 AM PST by ASA Vet ("Those who know, don't talk, those who talk, don't know.")
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To: PatrickHenry; thesummerwind
We are seeing the building blocks of molecular nanotechnology being created. Think of this "artifical DNA" as storage media for molecular assemblers!
5 posted on 02/24/2004 4:16:46 AM PST by marktwain
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To: PatrickHenry
What are the anti-evos gonna do now?

What they always do and move the goalpost.

You can't create a cat from scratch in laboratory now can you?

6 posted on 02/24/2004 4:32:56 AM PST by qam1 (Are Republicans the party of Reagan or the party of Bloomberg and Pataki?)
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To: PatrickHenry
These can be used to make forms of DNA that are more robust than the natural kind and do not break apart when exposed to high temperatures.

I hope this stuff doesn't escape in viral form. Ouch!

7 posted on 02/24/2004 4:41:20 AM PST by <1/1,000,000th%
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To: PatrickHenry
I'm not sure what you mean. Why is this a problem for "anti-evos?"
8 posted on 02/24/2004 4:45:17 AM PST by Lucas McCain
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To: qam1
You can't create a cat from scratch in laboratory now can you?

I can create scratches from a cat, does that count?


9 posted on 02/24/2004 4:51:10 AM PST by Ichneumon
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To: Ichneumon
Maine Coon?
10 posted on 02/24/2004 4:56:08 AM PST by Saturnalia (My name is Matt Foley and I live in a VAN down by the RIVER.)
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To: PatrickHenry
Odd, absent the assertions that the work was done by 'harnessing the principles of evolution' and that in the future the artificial genome 'might evolve on its own', it sounds a bit more like an instance of intelligent design than of evolution: intelligent actors select what enzymes to use. And, where is the 'selection' process in this if not in the scientist's minds and actions?

All your rhetoric does is prove that evolutionism, whatever its scientific roots, has beeome as much a closed, unfalsifiable system in the minds of its vocal proponents as creationism is in the minds of its.

11 posted on 02/24/2004 4:56:29 AM PST by The_Reader_David
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To: Ichneumon
What a beautiful cat!
12 posted on 02/24/2004 4:59:10 AM PST by kaylar
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To: The_Reader_David
I agree. Darwinians have not harnessed the principles of evolution. These scientists have used their intelligence to manipulate a piece of machinery.
13 posted on 02/24/2004 5:30:30 AM PST by adakota
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To: Ichneumon
How about a cat named Scratches?
14 posted on 02/24/2004 5:51:35 AM PST by js1138
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To: PatrickHenry
By systematically tinkering with the structure of DNA polymerase at one or two specific locations, researchers can make enzymes that work with artificial bases. But this technique, called 'rational design', is a tedious and unpredictable process.

"Going the full distance is very difficult to do in a rational way," says Rui Sousa of the University of Texas Health Science Center at San Antonio. Sousa has designed polymerases that are being used commercially.

Romesberg and his co-workers tried a different approach called 'directed evolution'. They made millions of mutant polymerases by randomly scrambling part of the natural enzyme's chemical structure. Most of the mutants were useless, but some were quite good at stitching together non-standard bases. They plucked these useful mutants out of the crowd, and repeated the mutation and selection process to fine-tune their abilities.

Hah! It's turning out that "intelligent design" IS variation and [some or other kind of] selection.
15 posted on 02/24/2004 5:57:18 AM PST by VadeRetro
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To: The_Reader_David
Is a computer simulation of a bouncing ball a priori inaccurate or incorrect merely because it takes place in an artificial, simulated environment?
16 posted on 02/24/2004 6:04:18 AM PST by general_re (Ubi solitudinem faciunt, pacem appellant. - Tacitus)
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To: PatrickHenry
When they can create life out of nothing, then I'll pay attention.
17 posted on 02/24/2004 6:07:30 AM PST by ZULU (GOD BLESS SENATOR McCARTHY!!!!)
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To: The_Reader_David
Post 15. It's turning out that the fast way to get anywhere in bio design is to "randomly" create a ton of variations and then do some kind of selection trials. Then you do another round with the survivors.

That is precisely the Darwinian model.

18 posted on 02/24/2004 6:11:10 AM PST by VadeRetro
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To: The_Reader_David
All your rhetoric does is prove that evolutionism, whatever its scientific roots, has become as much a closed, unfalsifiable system in the minds of its vocal proponents as creationism is in the minds of its.

Worth repeating! I especially liked the little addition to the title of the article.

Also from the original article (sub-title):

Guided evolution and HIV help create man-made stuff of life.

Has there ever been anything *but* guided "evolution"?

19 posted on 02/24/2004 6:45:08 AM PST by Michael_Michaelangelo
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To: PatrickHenry
"to find an enzyme capable of assembling non-standard DNA1."

If you're going to try to "create life" in a lab, you should start with your own material - not God's.

When scientists create something from nothing, I'll be the first in line to praise them!

ampu

20 posted on 02/24/2004 6:49:08 AM PST by aMorePerfectUnion (Hi! I'm John Kerry - and did I mention I was in Vietnam?)
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