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THIS WEEK 10 | NewScientist | 28 April 2012 ALL of a sudden, DNA has no reason to feel special. For decades it seemed that only a handful of molecules could store genetic information and pass it on. But now synthetic biologists have discovered that six others can pull off the same trick, and there may be many more to discover. The finding suggests that life on other planets need not be based on DNA – although re-running life on Earth would probably still have resulted in our DNA world (see “If I had my time again…”). The ability to copy information from one molecule to another is fundamental to all life. Organisms pass their genes to their offspring, often with small changes, and as a result life can evolve over the generations. Barring a few exceptions that rely on RNA, all known organisms use DNA as the information carrier. A host of alternative nucleic acids have been made in labs over the years, but none has shared DNA and RNA’s trick for copying genetic information – XNA: new to the gene scene A 500-million-year-old bacterial gene got a second chance at evolution this year. The experiment may help biologists understand the extent to which evolution is predictable. Biologists have long wondered whether life would evolve the same way again if we could rewind the tape. Eric Gaucher and Betül Arslan at Georgia Tech University in Atlanta hope to find out. They focused on EF-Tu, a gene in Escherichia coli that plays a crucial role in protein synthesis. Gaucher had previously worked out what this gene’s DNA sequence must have been 500 million years ago, by comparing the sequences of many modern bacteria and reasoning backwards. Now Arslan has synthesised the ancient gene and inserted it into E. coli in place of the modern version. The bacteria with the old gene grew less than half as fast as usual. Arslan then let eight bacterial lines evolve independently for 1000 generations. All eight lineages eventually grew faster — a sign that evolution had occurred. When Arslan sequenced their genomes, though, she found IF I HAD MY TIME AGAINSynthetic version of DNA created Michael Marshall the hallmark of heredity. Until now, that is. “This unique ability of DNA and RNA to encode information can be implemented in other backbones,” says Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK, whose team has done just that in six synthetic molecules. “Everyone thought we were limited to RNA and DNA,” says John Sutherland, also of the MRC Laboratory of Molecular Biology, who was not involved in the study. “This paper is a game-changer.” Holliger’s team focused on six XNAs (xeno-nucleic acids). DNA and RNA are made up of repeated units of a phosphate, a sugar and a base. The XNAs had different sugars, and in some of them the sugars are replaced with completely different molecules. The researchers then set out to create enzymes that could copy information from DNA to each of the XNAs, and other enzymes that could copy it back into DNA. They started with enzymes that do this in DNA only. Over the years the team tweaked them until they produced enzymes that could work on XNAs. Once they had created these enzymes, they were able to store information in each of the XNAs, copy it to DNA, and copy it back into a new XNA. In effect, the first XNA passed its information on to the second XNA – albeit via a DNA intermediary (Science, DOI: 10.1126/science.1217622). “The cycle we have is a bit like a retrovirus, which cycles between RNA and DNA,” Holliger says. This is the first time artificial molecules have been made to pass genes on to their descendants. Because the XNAs can do this, they are capable of evolution. “There is no overwhelming functional imperative to use DNA and RNA,” Holliger says. On other planets, where the chemistry is different, conditions might favour XNA. “I would be surprised if we find truly extraterrestrial life that was based on DNA and RNA,” he says. Holliger doubts that XNA was involved in the origin of life on Earth, though. Life may have begun with RNA simply because it was made in large quantities on the early Earth, before later switching to more stable DNA. “The question is whether these XNAs can be introduced into cells,” says Farren Isaacs of Yale University. Once the XNAs were installed, they could replicate and evolve on their own. “That would be remarkable.” n “This is the first time that artificial molecules have been made to pass genes on to their descendants” PASIEKA/SPL that EF-Tu was unchanged. What had evolved — differently in each lineage — were the genes that interact with EF-Tu. She reported the work at NASA’s Astrobiology Science Conference 2012 in Atlanta. The sheer number of interacting genes in protein synthesis means that random mutations are more likely to hit one of EF-Tu’s partners than EF-Tu itself. Eventually, though, EF-Tu may begin to evolve — either following the same path it began 500 million years ago or not. The experiment continues. Bob Holmes

Move over DNA: Six new molecules can carry genes

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THIS WEEK

10 | NewScientist | 28 April 2012

ALL of a sudden, DNA has no reason to feel special. For decades it seemed that only a handful of molecules could store genetic information and pass it on. But now synthetic biologists have discovered that six others can pull off the same trick, and there may be many more to discover.

The finding suggests that life on other planets need not be based on DNA – although re-running life on Earth would probably still have resulted in our DNA world (see “If I had my time again…”).

The ability to copy information from one molecule to another is fundamental to all life. Organisms pass their genes to their offspring, often with small changes, and as a result life can evolve over the generations. Barring a few exceptions that rely on RNA, all known organisms use DNA as the information carrier.

A host of alternative nucleic acids have been made in labs over the years, but none has shared DNA and RNA’s trick for copying genetic information –

XNA: new to the gene scene

A 500-million-year-old bacterial gene got a second chance at evolution this year. The experiment may help biologists understand the extent to which evolution is predictable.

Biologists have long wondered whether life would evolve the same way again if we could rewind the tape. Eric Gaucher and Betül Arslan at Georgia Tech University in Atlanta hope to find out.

They focused on EF-Tu, a gene in Escherichia coli that plays a crucial role in protein synthesis. Gaucher had previously worked out what this

gene’s DNA sequence must have been 500 million years ago, by comparing the sequences of many modern bacteria and reasoning backwards.

Now Arslan has synthesised the ancient gene and inserted it into E. coli in place of the modern version. The bacteria with the old gene grew less than half as fast as usual. Arslan then let eight bacterial lines evolve independently for 1000 generations.

All eight lineages eventually grew faster — a sign that evolution had occurred. When Arslan sequenced their genomes, though, she found

if i had my time again…

Synthetic version of dna createdMichael Marshall the hallmark of heredity.

Until now, that is. “This unique ability of DNA and RNA to encode information can be implemented in other backbones,” says Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK, whose team has done just that in six synthetic molecules.

“Everyone thought we were limited to RNA and DNA,” says John Sutherland, also of the MRC

Laboratory of Molecular Biology, who was not involved in the study. “This paper is a game-changer.”

Holliger’s team focused on six XNAs (xeno-nucleic acids). DNA and RNA are made up of repeated units of a phosphate, a sugar and a base. The XNAs had different sugars, and in some of them the sugars are replaced with completely different molecules.

The researchers then set out to create enzymes that could copy information from DNA to each of

the XNAs, and other enzymes that could copy it back into DNA.

They started with enzymes that do this in DNA only. Over the years the team tweaked them until they produced enzymes that could work on XNAs.

Once they had created these enzymes, they were able to store information in each of the XNAs, copy it to DNA, and copy it back into a new XNA. In effect, the first XNA passed its information on to the second XNA – albeit via a DNA

intermediary (Science, DOI: 10.1126/science.1217622).

“The cycle we have is a bit like a retrovirus, which cycles between RNA and DNA,” Holliger says.

This is the first time artificial molecules have been made to pass genes on to their descendants. Because the XNAs can do this, they are capable of evolution.

“There is no overwhelming functional imperative to use DNA and RNA,” Holliger says. On other planets, where the chemistry is different, conditions might favour XNA. “I would be surprised if we find truly extraterrestrial life that was based on DNA and RNA,” he says.

Holliger doubts that XNA was involved in the origin of life on Earth, though. Life may have begun with RNA simply because it was made in large quantities on the early Earth, before later switching to more stable DNA.

“The question is whether these XNAs can be introduced into cells,” says Farren Isaacs of Yale University. Once the XNAs were installed, they could replicate and evolve on their own. “That would be remarkable.” n

“this is the first time that artificial molecules have been made to pass genes on to their descendants”

PaSI

EKa

/SPl

that EF-Tu was unchanged. What had evolved — differently in each lineage — were the genes that interact with EF-Tu. She reported the work at NASA’s Astrobiology Science Conference 2012 in Atlanta.

The sheer number of interacting genes in protein synthesis means that random mutations are more likely to hit one of EF-Tu’s partners than EF-Tu itself. Eventually, though, EF-Tu may begin to evolve — either following the same path it began 500 million years ago or not. The experiment continues. Bob Holmes

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