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Synthetic Genetic Evolution

Scientists show that manmade nucleic acids can replicate and evolve, ushering in a new era in synthetic biology.

By | April 19, 2012

image: Synthetic Genetic Evolution Wikimedia Commons, Christoph Bock (Max Planck Institute for Informatics)

WIKIMEDIA COMMONS, CHRISTOPH BOCK (MAX PLANCK INSTITUTE FOR INFORMATICS)

Synthetic genetic polymers, broadly referred to as XNAs, can replicate and evolve just like their naturally occurring counterparts, DNA and RNA, according to a new study published today (April 19) in Science. The results of the research have implications not only for the fields of biotechnology and drug design, but also for research into the origins of life—on this planet and beyond.

“It’s a breakthrough,” said Gerald Joyce of The Scripps Research Institute in La Jolla, California, who was not involved in the study—“a beautiful paper in the realm of synthetic biology.”

“It shows that you don’t have to stick with the ribose and deoxyribose backbones of RNA and DNA in order to have transmittable, heritable, and evolvable information,” added Eric Kool of Stanford University, California, who also did not participate in the research.

Over the years, scientists have created a range of XNAs, in which the ribose or deoxyribose portions of RNA and DNA are replaced with alternative molecules. For example, threose is used to make TNA, and anhydrohexitol is used to make HNA. These polymers, which do not exist naturally, are generally studied with various biotechnological and therapeutic aims in mind.  But some researchers, like Philipp Holliger of the MRC Laboratory of Molecular Biology in Cambridge, UK, think XNAs might also provide insights into the origins of life. They might help to answer questions such as, “why is life based on DNA and RNA, and, if we ever find life beyond earth, is it likely to be based on the same molecule or could there be other possibilities?” Holliger said.

To get at some of these questions, Holliger and his colleagues had to first create enzymes that could replicate XNAs, a necessary first step to evolution. They did this both by randomly mutating and screening existing DNA polymerases for their ability to read XNA, and by an iterative process of selecting polymerase variants with capacities for XNA synthesis. In the end, they had several polymerases that could synthesize six different types of XNA.

To see whether XNAs could evolve, they generated random HNA sequences, then selected for those that could bind to two target molecules. After selection, the HNAs were amplified by the newly designed polymerases and again selected for their ability to bind the targets. Eight rounds of selection later, the HNA sequences were no longer random, as those with a particular target-binding motif became more abundant. Through selection and replication, the HNAs had evolved.

The finding in itself is not surprising, said Kool. “Chemists have been working for 20 years to find new backbones for DNA and the feeling always was that it would be interesting and quite possible that some of them might be replicated one day.” It was, nevertheless, impressive, he added. “The hard part was finding the enzymes that could do it. So the big leap ahead for this paper was finding those enzymes.”

The new polymerases synthesized XNA through rounds of DNA-to-XNA and XNA-to-DNA synthesis. Generating polymerases that can make XNA direct from XNA will be the next step, Holliger said, but it will be a lot harder “because both strands would be foreign to the polymerase.”

Holliger also explained that there was actually a benefit to having a DNA intermediate. “It allowed us to access the whole gamut of technologies that are available for analyzing DNA sequences.” Working with XNAs uniquely, he said, “is like being thrown back to the way molecular biology was in the early 1970s, in that we have to develop all our tools afresh.”

Holliger’s polymerases maybe the first addition to the XNA toolbox but, as more tools are created the potential for XNA biology will grow, said Jack Szostak of Harvard Medical School, who was not involved in the study. “In the longer run, it may be possible to design and build new forms of life that are based on one or more of these non-natural genetic polymers,” he said. That said, “I think it’s too early to say whether such novel life-forms would have any practical applications,” he added.

Regardless of what the future holds, the new polymerases could have applications right away. “We hope to be able to evolve XNA aptamers”—molecules that bind specific targets—“against medically interesting targets,” Holliger said. Scientists are already creating DNA and RNA aptamers, but their use in the body is severely hampered by their susceptibility to naturally occurring nucleases that degrade DNA and RNA. “XNAs are not natural and so are not susceptible to nucleases,” explained Joyce. “These things are bullet-proof.”

Beyond the medical applications of the work, Holliger is finally getting some answers about the basis of life. “The exciting finding of our work is that there really seems to be many possibilities,” he said. “There isn’t anything Goldilocks about DNA or RNA.” Does this mean that life elsewhere in the cosmos is more likely than previously thought? “I would say a cautious yes,” said Holliger.

V.B. Pinheiro et al., “Synthetic Genetic Polymers Capable of Heredity and Evolution,” Science, 336: 341-44, 2012.

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Comments

April 21, 2012

First thing first...Enzymes that could replicate XNA...Not from scratch as some use to say. It is just about how inheritance may start.

April 21, 2012

First thing first...Enzymes that could replicate XNA...Not from scratch as some use to say. It is just about how inheritance may start. A protein first, nor RNA enzyme that may have catalytic activity without regulatory power...A regulate catalytic activity, asymmetric distribution of ions as a form to harvest free energy change than life  as we now it and later inheritance.

Avatar of:

Posts: 0

April 21, 2012

First thing first...Enzymes that could replicate XNA...Not from scratch as some use to say. It is just about how inheritance may start.

Avatar of:

Posts: 0

April 21, 2012

First thing first...Enzymes that could replicate XNA...Not from scratch as some use to say. It is just about how inheritance may start. A protein first, nor RNA enzyme that may have catalytic activity without regulatory power...A regulate catalytic activity, asymmetric distribution of ions as a form to harvest free energy change than life  as we now it and later inheritance.

Avatar of:

Posts: 0

April 23, 2012

I just  hope none of that stuff escapes from the lab. ;-)

Avatar of: Jase Exum

Jase Exum

Posts: 1457

April 23, 2012

We are one step closer to proving that a deity was not needed to spark life.

Avatar of:

Posts: 0

April 23, 2012

We are one step closer to proving that a deity was not needed to spark life.

Avatar of: alberio792

alberio792

Posts: 1

April 23, 2012

I just  hope none of that stuff escapes from the lab. ;-)

Avatar of: danR

danR

Posts: 1457

April 26, 2012

I don't think it will do any harm.

Avatar of:

Posts: 0

April 26, 2012

I don't think it will do any harm.

Avatar of: Val Gee

Val Gee

Posts: 2

May 1, 2012

Jase Exum, I do not challenge your point, but I suggest that 'deity' must be defined before you can use the term to prove anything. As far back as we know of our own history, natural forces have been romanticized with a multitude of names and considered deities. This syndrome has given rise to much of the most deeply affecting literature, music, and art in our world. While 'God' hasn't created man, in the obvious ways, man has been provided with (and there are a multitude of delightful guesses there as to by what and by whom or how) the imagination to create the gods--and if people believe a god exists, then the very belief creates the god.

Avatar of: Val Gee

Val Gee

Posts: 2

May 1, 2012

Jase Exum, I'm not challenging your point, but I suggest that 'deity'
must be defined before anybody can use the term to prove anything. As far
back as we know of our own history, natural forces have been
romanticized and personified with a multitude of names and designated as deities. This syndrome has given rise to much of the most deeply affecting literature, music, and art in our world, to say nothing of spawning traditions. While a God may not have created man, in the literal sense, man has been provided with or enabled to develop imagination. There are a multitude of delightful hypotheses as to by what, by whom, and how. The imagination, and often a necessity for psychological survival, creation of gods indicates that if people believe a god exists, then that very belief creates the god.

Avatar of:

Posts: 0

May 1, 2012

Jase Exum, I do not challenge your point, but I suggest that 'deity' must be defined before you can use the term to prove anything. As far back as we know of our own history, natural forces have been romanticized with a multitude of names and considered deities. This syndrome has given rise to much of the most deeply affecting literature, music, and art in our world. While 'God' hasn't created man, in the obvious ways, man has been provided with (and there are a multitude of delightful guesses there as to by what and by whom or how) the imagination to create the gods--and if people believe a god exists, then the very belief creates the god.

Avatar of:

Posts: 0

May 1, 2012

Jase Exum, I'm not challenging your point, but I suggest that 'deity'
must be defined before anybody can use the term to prove anything. As far
back as we know of our own history, natural forces have been
romanticized and personified with a multitude of names and designated as deities. This syndrome has given rise to much of the most deeply affecting literature, music, and art in our world, to say nothing of spawning traditions. While a God may not have created man, in the literal sense, man has been provided with or enabled to develop imagination. There are a multitude of delightful hypotheses as to by what, by whom, and how. The imagination, and often a necessity for psychological survival, creation of gods indicates that if people believe a god exists, then that very belief creates the god.

Avatar of:

Posts: 0

May 18, 2012

Update Comprehension Of The Nature And Origin Of Earthlife:

Earth’s Primal Organisms (Per Sleep And Chirality)
AAAS Religion-Trade Union Dictates Notwithstanding
 
A.
Traces of Inaugural LifeGeologists, biologists join forces to tell new stories about the first cells on Earthhttp://www.sciencenews.or...
 
“Earth’s first living organisms didn’t leave behind footprints or bite marks or bones. These single cells thrived quietly in a tiny pocket somewhere on the planetâ€쳌.
 
B.
EarthLife Genesis From Aromaticity/H-Bonding
http://universe-life.com/2011/...
 
The address of Earth Life Genesis, of phasing from inanimate to animate natural selection, is Aromaticity.Hydrogen Bonding.
 
Dov Henis
(comments from 22nd century)
http://universe-life.com/

Avatar of:

Posts: 0

May 18, 2012

XNAs and XNA biology with its tool kit make us to witness Xmen and Xwomen of future generations with X-genome pitted against XY-Human genomes. It has given scientists to understand the molecular biology of life and is trying to carry mortals like us to the synthetic life zone. With very little tools of knowledge with all faults and frailty a human faces a huge challenge of facing science in the realm of artificial life created in the robotic sciences and now in natural science. It took Professor Watson and Crick to crack open the shell of DNA to look at the biochemical yolk of life. Now with Craig Venter's creation of a synthetic bacteria and the development of new science synthetic biology a new whole world of XNAs biology stare at us with bewildering possibilities and probabilities.
Life with its infinite variety and uncertainty make this globe a wonderful place keeping all of us humans bound with emotional nucleosomes and linker love histones. Where XNAs will take us the great scientists of molecular, synthetic biology and artificial intelligence may decide. As Dr.John Nash said let us not not forget the mysterious equations of love keep us living as loving beings and let us not convert ourselves into scientific zombies when we continue our stretch to understand the science of life. The great scientists contribute to the quality of life we live in today and we salute them as ordinary humans. Your scientific achievements protect us and hope that continues to do so.

Avatar of: Dov

Dov

Posts: 1457

May 18, 2012

Update Comprehension Of The Nature And Origin Of Earthlife:

Earth’s Primal Organisms (Per Sleep And Chirality)
AAAS Religion-Trade Union Dictates Notwithstanding
 
A.
Traces of Inaugural LifeGeologists, biologists join forces to tell new stories about the first cells on Earthhttp://www.sciencenews.or...
 
“Earth’s first living organisms didn’t leave behind footprints or bite marks or bones. These single cells thrived quietly in a tiny pocket somewhere on the planetâ€쳌.
 
B.
EarthLife Genesis From Aromaticity/H-Bonding
http://universe-life.com/2011/...
 
The address of Earth Life Genesis, of phasing from inanimate to animate natural selection, is Aromaticity.Hydrogen Bonding.
 
Dov Henis
(comments from 22nd century)
http://universe-life.com/

May 18, 2012

XNAs and XNA biology with its tool kit make us to witness Xmen and Xwomen of future generations with X-genome pitted against XY-Human genomes. It has given scientists to understand the molecular biology of life and is trying to carry mortals like us to the synthetic life zone. With very little tools of knowledge with all faults and frailty a human faces a huge challenge of facing science in the realm of artificial life created in the robotic sciences and now in natural science. It took Professor Watson and Crick to crack open the shell of DNA to look at the biochemical yolk of life. Now with Craig Venter's creation of a synthetic bacteria and the development of new science synthetic biology a new whole world of XNAs biology stare at us with bewildering possibilities and probabilities.
Life with its infinite variety and uncertainty make this globe a wonderful place keeping all of us humans bound with emotional nucleosomes and linker love histones. Where XNAs will take us the great scientists of molecular, synthetic biology and artificial intelligence may decide. As Dr.John Nash said let us not not forget the mysterious equations of love keep us living as loving beings and let us not convert ourselves into scientific zombies when we continue our stretch to understand the science of life. The great scientists contribute to the quality of life we live in today and we salute them as ordinary humans. Your scientific achievements protect us and hope that continues to do so.

Avatar of: hu zhang

hu zhang

Posts: 1

May 20, 2012

first create it

Avatar of:

Posts: 0

May 20, 2012

first create it

Avatar of:

Posts: 0

May 21, 2012

Not really, as the universe itself may have deistic qualities.  And it's beside the point that this experiment still uses biologically evolved elements as basic to the synthesis.

Avatar of: Roy Niles

Roy Niles

Posts: 32

May 21, 2012

Not really, as the universe itself may have deistic qualities.  And it's beside the point that this experiment still uses biologically evolved elements as basic to the synthesis.

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