Post by crystalriver on Nov 5, 2009 15:22:09 GMT -5
www.newscientist.com/article/dn13252
Two artificial DNA "letters" that are accurately and efficiently replicated by a natural enzyme have been created by US researchers. Adding the two artificial building blocks to the four that naturally comprise DNA could allow wildly different kinds of genetic engineering, they say.
Eventually, the researchers say, they may be able to add them into the genetic code of living organisms.
The diversity of life on earth evolved using genetic code made from arrangements of four genetic "bases", sometimes described as letters. They are divided into two pairs, which bond together from opposite strands of a DNA molecule to form the rungs of its characteristic double-helix shape.
The unnatural but functional new base pair is the fruit of nearly a decade of research by chemical biologist Floyd Romesberg, at the Scripps Research Institute, La Jolla, California, US.
Romesberg and colleagues painstakingly created a library of nearly 200 potential new genetic bases that are slight variations on the natural ones. Unfortunately, none of them were similar enough in structure and chemistry to the real thing to be copied accurately by the polymerase enzymes that replicate DNA inside cells.
Random generation
Frustrated by the slow pace designing and synthesising potential new bases one at a time, Romesberg borrowed some tricks from drug development companies. The resulting large scale experiments generated many potential bases at random, which were then screened to see if they would be treated normally by a polymerase enzyme.
With the help of graduate student Aaron Leconte, the group synthesized and screened 3600 candidates. Two different screening approaches turned up the same pair of molecules, called dSICS and dMMO2.
The molecular pair that worked surprised Romesberg. "We got it and said, 'Wow!' It would have been very difficult to have designed that pair rationally."
But the team still faced a challenge. The dSICS base paired with itself more readily than with its intended partner, so the group made minor chemical tweaks until the new compounds behaved properly.
Novel DNA
"We probably made 15 modifications," says Romesberg, "and 14 made it worse." Sticking a carbon atom attached to three hydrogen atoms onto the side of dSICS, changing it to d5SICS, finally solved the problem. "We now have an unnatural base pair that's efficiently replicated and doesn't need an unnatural polymerase," says Romesberg. "It's staring to behave like a real base pair."
The team is now eager to find out just what makes it work. "We still don't have a detailed understanding of how replication happens," says Romesberg. "Now that we have an unnatural base pair, we are continuing experiments to understand it better."
In the near future, Romesberg expects the new base pairs will be used to synthesize DNA with novel and unnatural properties. These might include highly specific primers for DNA amplification; tags for materials, such as explosives, that could be detected without risk of contamination from natural DNA; and building novel DNA-based nanomaterials.
Increased 'evolvability'
More generally, Romesberg notes that DNA and RNA are now being used for hundreds of purposes: for example, to build complex shapes, build complex nanostructures, silence disease genes, or even perform calculations. A new, unnatural, base pair could multiply and diversify these applications.
The most challenging goal, says Romesberg, will be to incorporate unnatural base pairs into the genetic code of organisms. "We want to import these into a cell, study RNA trafficking, and in the longest term, expand the genetic code and 'evolvability' of an organism."
Stanford University chemist Eric Kool, has studied the fundamental chemistry of base-pair bonding. He foresees challenges, but great potential in the unnatural bases.
"It requires a long effort by multiple laboratories, but I think ultimately it will lead to some important tools," he says. "The ability to encode amino acids with unnatural base pairs will be quite powerful when it comes."
Journal reference: Journal of the American Chemical Society (DOI: 10.1021/ja078223d)
Genetics - Keep up with the pace in our continually updated special report.
If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.
Have your say
Comment title Your name Email Website Comment
read all 51 comments Comments 1 | 2 | 3 | 4 | 5 | 6 Word
Wed Jan 30 16:11:42 GMT 2008 by Word
Word. Genetic engineering. Lets make manbearpigs.
reply report this comment Word
Wed Jan 30 16:43:21 GMT 2008 by Excel
Or have sharks with frickin' laser beams.
reply report this comment view thread
Word
Wed Jan 30 17:21:57 GMT 2008 by John W. Blount
Better word up. 'Hubris'.
Our stupid pride makes us suckers for stupid stuff. In several senses, this is one of the stupidest things I have ever heard.
There may be good and legitimate uses for this mess, but going on past record, if there is a way to screw it up, we'll do it just to see what happens. "Hey, this works! Let's improve on human DNA, make it more 'evolvable'!"
GOOD GRIEF!
Mankind already has the 'word' for our tombstone, 'Hey guys! Look at this!'
reply report this comment Word
Wed Jan 30 18:14:37 GMT 2008 by Gadget
I can only imagine all the discoveries that led up to YOU being able to share your opinion with the entire planet (i.e. Electricity, medicine, etc.). Yet here you are, typing away, living past 30 (I assume), and possibly even have all you teeth.
A bleak future won't be the result of discovery; it will be the result of ignorance.
By the way, the earth is not flat
reply report this comment Word
Fri Feb 01 00:16:30 GMT 2008 by Zentub
Interestingly that is hwat this discovery is about.
It is hoped that using a new life form we will have the means to create cheap/free energy and a way to clean up the mess of a century of fossil fuel.
It will be a way to give the entire population of the planet a lifestyle like that of the top three without having to go and find a few more earths to mine the guts out of.
Something like that discovery of powering your home using bacteria.
reply report this comment 2 more replies
view thread
Word
Wed Jan 30 18:54:12 GMT 2008 by Redx
Well yeah, we needed the extra genetic bases so it could be 50% man, 50% bear and 50% pig.
The math doesn't work with only 4 base pairs, but now that we have a 150% increase in available pairs, we can do it.
reply report this comment Word
Thu Jan 31 01:34:52 GMT 2008 by Ferro
Buahahahahaha all we need now after this is a certain man bear pig hunter to kill of this genetic monstrosity that is bound to come one day or another
reply report this comment view thread
Word
Thu Jan 31 06:46:55 GMT 2008 by Windy
I would imagine that the intention of creating the new artifical "DNA letters" the genetic engineering of novel new drug therapies.
So I don't think they are talking about wanting to manipulate man-bear-pigs or whatever.
But the problem is that we don't know enough about how these artificial DNA letters will react inside animal or human bodies.
They'll do lab testing, of course, and these new drugs with the artificial DNA letters may even pass those tests.
But I am still worried. Nature adapts herself in unforseen ways, and once these things are "out there" we have no idea how they will interact with the natural environment.
So there is good reason to be worried.
reply report this comment Word
Fri Feb 01 13:48:09 GMT 2008 by Rationalthinker
There is no such thing as "Nature" with some bizarre female attributes. Also, nothing that exists can be "unnatural"
reply report this comment Word
Fri Feb 01 15:25:56 GMT 2008 by Boss
I'm so glad that someone else is as bugged as I am by people calling things 'unnatural' that just aren't!
reply report this comment Word
Fri Feb 01 15:42:48 GMT 2008 by Mark Mywords
Chemical biologist Floyd Romesberg, himself, said "unnaturual" at least twice in the article. Let's figure he knows what he's talking about, shall we? I'm sure that by "unnatural" he meant "something that doesn't already exist in nature but requires to be human-made."
reply report this comment 1 more reply
view thread
Viabilty?
Wed Jan 30 16:34:47 GMT 2008 by Allaun
Is there proof that this new base pair would be inherited by the organisms offspring? And could introducing a artificial base pair cause replication errors due to interference? Or even introduce rejection from the host organism? That said, It's quite a accomplishment. To find a novel way of creating new building blocks is a laudable goal. And because it seems like a perfect quote..... "There what you call a survivor?"
"A few cells are still alive, it's more than I need."
"Could you at least idenfity it?"
"We tried. But the computer went off the charts. You see, normal human beings have 40 DNA memo groups, which is more than enough for any species to perpetuate itself. This has 200,000... The cell is for the lack of a better word... Perfect."
"This is a normal human DNA chain. Ok? You, me, anybody, right? Watch this... The compositional elements of this DNA chain are the same as ours. There's simply more of them, tightly packed with infinite genetic knowledge. Almost like this being was engineered."
reply report this comment All Your Base Are Belong To Us
Wed Jan 30 16:43:34 GMT 2008 by Monkey Liar
Awesome use of a 5th element quote there dude.
This sounds like a tool of the future in the making to me...
reply report this comment All Your Base Are Belong To Us
Fri Jun 27 23:21:55 BST 2008 by Carlos Romero
Who funds this sort of research? I guess the taxes that the ignorant majority pays so that a few "curious scientist" will determine what the sex of angels is...
Scripps.. Wake up! there are people in America starving even though their 4-letter genetic code is healthy and hungry... Put your research money to work on something constructive
reply report this comment view thread
read all 51 comments Comments 1 | 2 | 3 | 4 | 5 | 6 All comments should respect the New Scientist House Rules. If you think a particular comment breaks these rules then please use the "Report" link in that comment to report it to us.
If you are having a technical problem posting a comment, please contact technical support.
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Two artificial DNA "letters" that are accurately and efficiently replicated by a natural enzyme have been created by US researchers. Adding the two artificial building blocks to the four that naturally comprise DNA could allow wildly different kinds of genetic engineering, they say.
Eventually, the researchers say, they may be able to add them into the genetic code of living organisms.
The diversity of life on earth evolved using genetic code made from arrangements of four genetic "bases", sometimes described as letters. They are divided into two pairs, which bond together from opposite strands of a DNA molecule to form the rungs of its characteristic double-helix shape.
The unnatural but functional new base pair is the fruit of nearly a decade of research by chemical biologist Floyd Romesberg, at the Scripps Research Institute, La Jolla, California, US.
Romesberg and colleagues painstakingly created a library of nearly 200 potential new genetic bases that are slight variations on the natural ones. Unfortunately, none of them were similar enough in structure and chemistry to the real thing to be copied accurately by the polymerase enzymes that replicate DNA inside cells.
Random generation
Frustrated by the slow pace designing and synthesising potential new bases one at a time, Romesberg borrowed some tricks from drug development companies. The resulting large scale experiments generated many potential bases at random, which were then screened to see if they would be treated normally by a polymerase enzyme.
With the help of graduate student Aaron Leconte, the group synthesized and screened 3600 candidates. Two different screening approaches turned up the same pair of molecules, called dSICS and dMMO2.
The molecular pair that worked surprised Romesberg. "We got it and said, 'Wow!' It would have been very difficult to have designed that pair rationally."
But the team still faced a challenge. The dSICS base paired with itself more readily than with its intended partner, so the group made minor chemical tweaks until the new compounds behaved properly.
Novel DNA
"We probably made 15 modifications," says Romesberg, "and 14 made it worse." Sticking a carbon atom attached to three hydrogen atoms onto the side of dSICS, changing it to d5SICS, finally solved the problem. "We now have an unnatural base pair that's efficiently replicated and doesn't need an unnatural polymerase," says Romesberg. "It's staring to behave like a real base pair."
The team is now eager to find out just what makes it work. "We still don't have a detailed understanding of how replication happens," says Romesberg. "Now that we have an unnatural base pair, we are continuing experiments to understand it better."
In the near future, Romesberg expects the new base pairs will be used to synthesize DNA with novel and unnatural properties. These might include highly specific primers for DNA amplification; tags for materials, such as explosives, that could be detected without risk of contamination from natural DNA; and building novel DNA-based nanomaterials.
Increased 'evolvability'
More generally, Romesberg notes that DNA and RNA are now being used for hundreds of purposes: for example, to build complex shapes, build complex nanostructures, silence disease genes, or even perform calculations. A new, unnatural, base pair could multiply and diversify these applications.
The most challenging goal, says Romesberg, will be to incorporate unnatural base pairs into the genetic code of organisms. "We want to import these into a cell, study RNA trafficking, and in the longest term, expand the genetic code and 'evolvability' of an organism."
Stanford University chemist Eric Kool, has studied the fundamental chemistry of base-pair bonding. He foresees challenges, but great potential in the unnatural bases.
"It requires a long effort by multiple laboratories, but I think ultimately it will lead to some important tools," he says. "The ability to encode amino acids with unnatural base pairs will be quite powerful when it comes."
Journal reference: Journal of the American Chemical Society (DOI: 10.1021/ja078223d)
Genetics - Keep up with the pace in our continually updated special report.
If you would like to reuse any content from New Scientist, either in print or online, please contact the syndication department first for permission. New Scientist does not own rights to photos, but there are a variety of licensing options available for use of articles and graphics we own the copyright to.
Have your say
Comment title Your name Email Website Comment
read all 51 comments Comments 1 | 2 | 3 | 4 | 5 | 6 Word
Wed Jan 30 16:11:42 GMT 2008 by Word
Word. Genetic engineering. Lets make manbearpigs.
reply report this comment Word
Wed Jan 30 16:43:21 GMT 2008 by Excel
Or have sharks with frickin' laser beams.
reply report this comment view thread
Word
Wed Jan 30 17:21:57 GMT 2008 by John W. Blount
Better word up. 'Hubris'.
Our stupid pride makes us suckers for stupid stuff. In several senses, this is one of the stupidest things I have ever heard.
There may be good and legitimate uses for this mess, but going on past record, if there is a way to screw it up, we'll do it just to see what happens. "Hey, this works! Let's improve on human DNA, make it more 'evolvable'!"
GOOD GRIEF!
Mankind already has the 'word' for our tombstone, 'Hey guys! Look at this!'
reply report this comment Word
Wed Jan 30 18:14:37 GMT 2008 by Gadget
I can only imagine all the discoveries that led up to YOU being able to share your opinion with the entire planet (i.e. Electricity, medicine, etc.). Yet here you are, typing away, living past 30 (I assume), and possibly even have all you teeth.
A bleak future won't be the result of discovery; it will be the result of ignorance.
By the way, the earth is not flat
reply report this comment Word
Fri Feb 01 00:16:30 GMT 2008 by Zentub
Interestingly that is hwat this discovery is about.
It is hoped that using a new life form we will have the means to create cheap/free energy and a way to clean up the mess of a century of fossil fuel.
It will be a way to give the entire population of the planet a lifestyle like that of the top three without having to go and find a few more earths to mine the guts out of.
Something like that discovery of powering your home using bacteria.
reply report this comment 2 more replies
view thread
Word
Wed Jan 30 18:54:12 GMT 2008 by Redx
Well yeah, we needed the extra genetic bases so it could be 50% man, 50% bear and 50% pig.
The math doesn't work with only 4 base pairs, but now that we have a 150% increase in available pairs, we can do it.
reply report this comment Word
Thu Jan 31 01:34:52 GMT 2008 by Ferro
Buahahahahaha all we need now after this is a certain man bear pig hunter to kill of this genetic monstrosity that is bound to come one day or another
reply report this comment view thread
Word
Thu Jan 31 06:46:55 GMT 2008 by Windy
I would imagine that the intention of creating the new artifical "DNA letters" the genetic engineering of novel new drug therapies.
So I don't think they are talking about wanting to manipulate man-bear-pigs or whatever.
But the problem is that we don't know enough about how these artificial DNA letters will react inside animal or human bodies.
They'll do lab testing, of course, and these new drugs with the artificial DNA letters may even pass those tests.
But I am still worried. Nature adapts herself in unforseen ways, and once these things are "out there" we have no idea how they will interact with the natural environment.
So there is good reason to be worried.
reply report this comment Word
Fri Feb 01 13:48:09 GMT 2008 by Rationalthinker
There is no such thing as "Nature" with some bizarre female attributes. Also, nothing that exists can be "unnatural"
reply report this comment Word
Fri Feb 01 15:25:56 GMT 2008 by Boss
I'm so glad that someone else is as bugged as I am by people calling things 'unnatural' that just aren't!
reply report this comment Word
Fri Feb 01 15:42:48 GMT 2008 by Mark Mywords
Chemical biologist Floyd Romesberg, himself, said "unnaturual" at least twice in the article. Let's figure he knows what he's talking about, shall we? I'm sure that by "unnatural" he meant "something that doesn't already exist in nature but requires to be human-made."
reply report this comment 1 more reply
view thread
Viabilty?
Wed Jan 30 16:34:47 GMT 2008 by Allaun
Is there proof that this new base pair would be inherited by the organisms offspring? And could introducing a artificial base pair cause replication errors due to interference? Or even introduce rejection from the host organism? That said, It's quite a accomplishment. To find a novel way of creating new building blocks is a laudable goal. And because it seems like a perfect quote..... "There what you call a survivor?"
"A few cells are still alive, it's more than I need."
"Could you at least idenfity it?"
"We tried. But the computer went off the charts. You see, normal human beings have 40 DNA memo groups, which is more than enough for any species to perpetuate itself. This has 200,000... The cell is for the lack of a better word... Perfect."
"This is a normal human DNA chain. Ok? You, me, anybody, right? Watch this... The compositional elements of this DNA chain are the same as ours. There's simply more of them, tightly packed with infinite genetic knowledge. Almost like this being was engineered."
reply report this comment All Your Base Are Belong To Us
Wed Jan 30 16:43:34 GMT 2008 by Monkey Liar
Awesome use of a 5th element quote there dude.
This sounds like a tool of the future in the making to me...
reply report this comment All Your Base Are Belong To Us
Fri Jun 27 23:21:55 BST 2008 by Carlos Romero
Who funds this sort of research? I guess the taxes that the ignorant majority pays so that a few "curious scientist" will determine what the sex of angels is...
Scripps.. Wake up! there are people in America starving even though their 4-letter genetic code is healthy and hungry... Put your research money to work on something constructive
reply report this comment view thread
read all 51 comments Comments 1 | 2 | 3 | 4 | 5 | 6 All comments should respect the New Scientist House Rules. If you think a particular comment breaks these rules then please use the "Report" link in that comment to report it to us.
If you are having a technical problem posting a comment, please contact technical support.
PRINTSEND ADVERTISEMENT
MoreLatest newsSony demos game controller to track motion and emotion
14:57 05 November 2009
Sony looks set to be the first major console maker to bring hands-free, full-body game control to the public
TV switch-over triggers rush to see rare stars
14:14 05 November 2009
The wavelengths previously used to broadcast analogue TV in the US are now open to radio astronomers – but not for long
Virtual crashes and clatters get real
22:00 04 November 2009
Sounds like the clash of a cymbal used to take weeks for software to mimic – now they can be synthesised in hours
SMSes offer smart apps to basic cellphones