New Study Contradicts the ‘Metabolism First’ Hypothesis

Image of what would be a “compound genome”. Different molecules (in various colours) join the globule or corpuscle, which divides once it reaches a critical size. (Credit: Image provided by Doron Lancet)

Universitat Autonoma de Barcelona, January 25, 2010 — A new study published in Proceedings of National Academy of Sciences rejects the theory that the origin of life stems from a system of self-catalytic molecules capable of experiencing Darwinian evolution without the need of RNA or DNA and their replication.

The research, which was carried out with the participation of Mauro Santos, researcher of the Department of Genetics and Microbiology at Universitat Autònoma de Barcelona (UAB), has demonstrated that, through the analysis of what some researchers name “compound genomes,” these chemical networks cannot be considered evolutionary units because they lose properties which are essential for evolution when they reach a critical size and greater level of complexity.

The U.S. National Aeronautics and Space Administration (NASA) defines life as a “self-sustaining chemical system capable of Darwinian evolution.” The scientific theories on the origin of life revolve around two main ideas: one focuses on genetics — with RNA or DNA replication as an essential condition for Darwinian evolution to take place — and the other focuses on metabolism. It is clear that both situations must have begun with simple organic molecules formed by prebiotic processes, as was demonstrated by the Miller-Urey experiment (in which organic molecules were created from inorganic substances). The point in which these two theories differ is that the replication of RNA or DNA molecules is a far too complex process which requires a correct combination of monomers within the polymers to produce a molecular chain resulting from the replication.

Until now no plausible chemical explanation exists for how these processes occured. In addition, defenders of the second theory argue that the processes needed for evolution to take place depend on primordial metabolism. This metabolism is believed to be a type of chemical network entailing a high degree of mutual catalysis between its components which, in turn, eventually allows for adaptation and evolution without any molecular replication.

In the first half of the 20th century, Alexander Oparin established the “Metabolism First” hypothesis to explain the origin of life, thus strengthening the primary role of cells as small drops of coacervates (evolutionary precursors of the first prokaryote cells). Dr Oparin did not refer to RNA or DNA molecules since at that time it was not clear just how important the role of these molecules was in living organisms. However he did form a solid base for the idea of self-replication as a collective property of molecular compounds.

Science more recently demonstrated that sets of chemical components store information about their composition which can be duplicated and transmitted to their descendents. This has led to their being named “compound genomes” or composomes. In other words, heredity does not require information in order to be stored in RNA or DNA molecules. These “compound genomes” apparently fulfil the conditions required to be considered evolutionary units, which suggests a pathway from pre-Darwinian dynamics to a minimum protocell.

Researchers in this study nevertheless reveal that these systems are incapable of undergoing a Darwinian evolution. For the first time a rigorous analysis was carried out to study the supposed evolution of these molecular networks using a combination of numerical and analytical simulations and network analysis approximations. Their research demonstrated that the dynamics of molecular compound populations which divide after having reached a critical size do not evolve, since during this process the compounds lose properties which are essential for Darwinian evolution.

Researchers concluded that this fundamental limitation of “compound genomes” should lead to caution towards theories that set metabolism first as the origin as life, even though former metabolic systems could have offered a stable habitat in which primitive polymers such as RNA could have evolved.

Researchers state that different prebiotic Earth scenarios can be considered. However, the basic property of life as a system capable of undergoing Darwinian evolution began when genetic information was finally stored and transmitted such as occurs in nucleotide polymers (RNA and DNA).

RNA That Replicates Itself Indefinitely

Rendering of DNA molecules. Scientists have synthesized for the first time RNA enzymes that can replicate themselves without the help of any proteins or other cellular components, and the process proceeds indefinitely. (Credit: iStockphoto)

 

 

Scripps Research Institute — One of the most enduring questions is how life could have begun on Earth. Molecules that can make copies of themselves are thought to be crucial to understanding this process as they provide the basis for heritability, a critical characteristic of living systems. New findings could inform biochemical questions about how life began.

Now, a pair of Scripps Research Institute scientists has taken a significant step toward answering that question. The scientists have synthesized for the first time RNA enzymes that can replicate themselves without the help of any proteins or other cellular components, and the process proceeds indefinitely.  The work was published in the journal Science.

In the modern world, DNA carries the genetic sequence for advanced organisms, while RNA is dependent on DNA for performing its roles such as building proteins. But one prominent theory about the origins of life, called the RNA World model, postulates that because RNA can function as both a gene and an enzyme, RNA might have come before DNA and protein and acted as the ancestral molecule of life. However, the process of copying a genetic molecule, which is considered a basic qualification for life, appears to be exceedingly complex, involving many proteins and other cellular components.

For years, researchers have wondered whether there might be some simpler way to copy RNA, brought about by the RNA itself. Some tentative steps along this road had previously been taken by the Joyce lab and others, but no one could demonstrate that RNA replication could be self-propagating, that is, result in new copies of RNA that also could copy themselves.

In Vitro Evolution

A few years after Tracey Lincoln arrived at Scripps Research from Jamaica to pursue her Ph.D., she began exploring the RNA-only replication concept along with her advisor, Professor Gerald Joyce, M.D., Ph.D., who is also Dean of the Faculty at Scripps Research. Their work began with a method of forced adaptation known as in vitro evolution. The goal was to take one of the RNA enzymes already developed in the lab that could perform the basic chemistry of replication, and improve it to the point that it could drive efficient, perpetual self-replication.

Lincoln synthesized in the laboratory a large population of variants of the RNA enzyme that would be challenged to do the job, and carried out a test-tube evolution procedure to obtain those variants that were most adept at joining together pieces of RNA.

Ultimately, this process enabled the team to isolate an evolved version of the original enzyme that is a very efficient replicator, something that many research groups, including Joyce’s, had struggled for years to obtain. The improved enzyme fulfilled the primary goal of being able to undergo perpetual replication. “It kind of blew me away,” says Lincoln.

Immortalizing Molecular Information

The replicating system actually involves two enzymes, each composed of two subunits and each functioning as a catalyst that assembles the other. The replication process is cyclic, in that the first enzyme binds the two subunits that comprise the second enzyme and joins them to make a new copy of the second enzyme; while the second enzyme similarly binds and joins the two subunits that comprise the first enzyme. In this way the two enzymes assemble each other — what is termed cross-replication. To make the process proceed indefinitely requires only a small starting amount of the two enzymes and a steady supply of the subunits.

“This is the only case outside biology where molecular information has been immortalized,” says Joyce.

Not content to stop there, the researchers generated a variety of enzyme pairs with similar capabilities. They mixed 12 different cross-replicating pairs, together with all of their constituent subunits, and allowed them to compete in a molecular test of survival of the fittest. Most of the time the replicating enzymes would breed true, but on occasion an enzyme would make a mistake by binding one of the subunits from one of the other replicating enzymes. When such “mutations” occurred, the resulting recombinant enzymes also were capable of sustained replication, with the most fit replicators growing in number to dominate the mixture. “To me that’s actually the biggest result,” says Joyce.

The research shows that the system can sustain molecular information, a form of heritability, and give rise to variations of itself in a way akin to Darwinian evolution. So, says Lincoln, “What we have is non-living, but we’ve been able to show that it has some life-like properties, and that was extremely interesting.”

Knocking on the Door of Life

The group is pursuing potential applications of their discovery in the field of molecular diagnostics, but that work is tied to a research paper currently in review, so the researchers can’t yet discuss it.

But the main value of the work, according to Joyce, is at the basic research level. “What we’ve found could be relevant to how life begins, at that key moment when Darwinian evolution starts.” He is quick to point out that, while the self-replicating RNA enzyme systems share certain characteristics of life, they are not themselves a form of life.

The historical origin of life can never be recreated precisely, so without a reliable time machine, one must instead address the related question of whether life could ever be created in a laboratory. This could, of course, shed light on what the beginning of life might have looked like, at least in outline. “We’re not trying to play back the tape,” says Lincoln of their work, “but it might tell us how you go about starting the process of understanding the emergence of life in the lab.”

Joyce says that only when a system is developed in the lab that has the capability of evolving novel functions on its own can it be properly called life. “We’re knocking on that door,” he says, “But of course we haven’t achieved that.”

The subunits in the enzymes the team constructed each contain many nucleotides, so they are relatively complex and not something that would have been found floating in the primordial ooze. But, while the building blocks likely would have been simpler, the work does finally show that a simpler form of RNA-based life is at least possible, which should drive further research to explore the RNA World theory of life’s origins.


ScienceDaily.com — With the aid of a straightforward experiment, researchers have provided some clues to one of biology’s most complex questions: how ancient organic molecules came together to form the basis of life.

Specifically, this study demonstrated how ancient RNA joined together to reach a biologically relevant length.

RNA, the single-stranded precursor to DNA, normally expands one nucleic base at a time, growing sequentially like a linked chain. The problem is that in the primordial world RNA molecules didn’t have enzymes to catalyze this reaction, and while RNA growth can proceed naturally, the rate would be so slow the RNA could never get more than a few pieces long (for as nucleic bases attach to one end, they can also drop off the other).

Ernesto Di Mauro and colleagues examined if there was some mechanism to overcome this thermodynamic barrier, by incubating short RNA fragments in water of different temperatures and pH.

They found that under favorable conditions (acidic environment and temperature lower than 70 degrees Celsius), pieces ranging from 10-24 in length could naturally fuse into larger fragments, generally within 14 hours.

The RNA fragments came together as double-stranded structures then joined at the ends. The fragments did not have to be the same size, but the efficiency of the reactions was dependent on fragment size (larger is better, though efficiency drops again after reaching around 100) and the similarity of the fragment sequences.

The researchers note that this spontaneous fusing, or ligation, would a simple way for RNA to overcome initial barriers to growth and reach a biologically important size; at around 100 bases long, RNA molecules can begin to fold into functional, 3D shapes.


Story Source: Adapted from materials provided by American Society for Biochemistry and Molecular Biology

Stardust from Murchison-meteorite. New finding suggests that parts of the raw materials to make the first molecules of DNA and RNA may have come from the stars. (Credit: Argonne National Laboratory, Department of Energy)

 

 

Imperial College London — Scientists confirmed over a year ago, that an important component of early genetic material which has been found in meteorite fragments is extraterrestrial in origin..

The finding suggests that parts of the raw materials to make the first molecules of DNA and RNA may have come from the stars.

The scientists, from Europe and the USA, say that their research provides evidence that life’s raw materials came from sources beyond the Earth.

The materials they have found include the molecules uracil and xanthine, which are precursors to the molecules that make up DNA and RNA, and are known as nucleobases.

The team discovered the molecules in rock fragments of the Murchison meteorite, which crashed in Australia in 1969.

They tested the meteorite material to determine whether the molecules came from the solar system or were a result of contamination when the meteorite landed on Earth.

The analysis shows that the nucleobases contain a heavy form of carbon which could only have been formed in space. Materials formed on Earth consist of a lighter variety of carbon.

Lead author Dr Zita Martins, of the Department of Earth Science and Engineering at Imperial College London, says that the research may provide another piece of evidence explaining the evolution of early life. She says:

“We believe early life may have adopted nucleobases from meteoritic fragments for use in genetic coding which enabled them to pass on their successful features to subsequent generations.”

Between 3.8 to 4.5 billion years ago large numbers of rocks similar to the Murchison meteorite rained down on Earth at the time when primitive life was forming. The heavy bombardment would have dropped large amounts of meteorite material to the surface on planets like Earth and Mars.

Co-author Professor Mark Sephton, also of Imperial’s Department of Earth Science and Engineering, believes this research is an important step in understanding how early life might have evolved. He added:

“Because meteorites represent left over materials from the formation of the solar system, the key components for life — including nucleobases — could be widespread in the cosmos. As more and more of life’s raw materials are discovered in objects from space, the possibility of life springing forth wherever the right chemistry is present becomes more likely.”

Light becomes polarized in detectable ways when reflected from chlorophyll and other chiral molecules necessary to life, so scientists working at NIST have built a device that can detect this polarization–potentially offering a way to find extraterrestrial life from great distances. Their device has already proved itself able to discern the polarized light scattered from the chlorophyll in leaves and also cyanobacteria (image), one-celled organisms that evolved early in the history of life on Earth. (Credit: Roger Burks (University of California at Riverside), Mark Schneegurt (Wichita State University), and Cyanosite (www-cyanosite.bio.purdue.edu))

 

 

National Institute of Standards and Technology — Visiting aliens may be the stuff of legend, but if a scientific team working at the National Institute of Standards and Technology (NIST) is right, we may be able to find extraterrestrial life even before it leaves its home planet—by looking for left- (or right-) handed light.

The technique the team has developed for detecting life elsewhere in the universe will not spot aliens directly. Rather, it could allow spaceborne instruments to see a telltale sign that life may have influenced a landscape: a preponderance of molecules that have a certain “chirality,” or handedness. A right-handed molecule has the same composition as its left-handed cousin, but their chemical behavior differs. Because many substances critical to life favor a particular handedness, Thom Germer and his colleagues think chirality might reveal life’s presence at great distances, and have built a device to detect it.

“You don’t want to limit yourself to looking for specific materials like oxygen that Earth creatures use, because that makes assumptions about what life is,” says Germer, a physicist at NIST. “But amino acids, sugars, DNA—each of these substances is either right- or left-handed in every living thing.”

Many molecules not associated with life exhibit handedness as well. But when organisms reproduce, their offspring possess chiral molecules that have the same handedness as those in their parents’ bodies. As life spreads, the team theorizes, the landscape will eventually have a large amount of molecules that favor one handedness.

“If the surface had just a collection of random chiral molecules, half would go left, half right,” Germer says. “But life’s self-assembly means they all would go one way. It’s hard to imagine a planet’s surface exhibiting handedness without the presence of self assembly, which is an essential component of life.”

Because chiral molecules reflect light in a way that indicates their handedness, the research team built a device to shine light on plant leaves and bacteria, and then detect the polarized reflections from the organisms’ chlorophyll from a short distance away. The device detected chirality from both sources.

The team intends to improve its detector so it can look at pond surfaces and then landscape-sized regions on Earth. Provided the team continues to get good results, Germer says, they will propose that it be built into a large telescope or mounted on a space probe.

“We need to be sure we get a signal from our own planet before we can look at others,” he says. “But what’s neat about the concept is that it is sensitive to something that comes from the process behind organic self-assembly, but not necessarily life as we know it.”

Funding for this research was provided by STSI and the European Space Agency.

A simulated ribosome (white and purple subunits) processing an amino acid (green). (Credit: Courtesy Los Alamos National Laboratory)

 

 

American Chemical Society — Flash back three or four billion years — Earth is a hot, dry and lifeless place. All is still. Without warning, a meteor slams into the desert plains at over ten thousand miles per hour. With it, this violent collision may have planted the chemical seeds of life on Earth.

Scientists have presented evidence that desert heat, a little water, and meteorite impacts may have been enough to cook up one of the first prerequisites for life: The dominance of “left-handed” amino acids, the building blocks of life on this planet.

In a report at the 235th national meeting of the American Chemical Society, Ronald Breslow, Ph.D., University Professor, Columbia University, and former ACS President, described how our amino acid signature came from outer space.

Chains of amino acids make up the protein found in people, plants, and all other forms of life on Earth. There are two orientations of amino acids, left and right, which mirror each other in the same way your hands do. This is known as “chirality.” In order for life to arise, proteins must contain only one chiral form of amino acids, left or right, Breslow noted.

“If you mix up chirality, a protein’s properties change enormously. Life couldn’t operate with just random mixtures of stuff,” he said.

With the exception of a few right-handed amino acid-based bacteria, left-handed “L-amino acids” dominate on earth. The Columbia University chemistry professor said that amino acids delivered to Earth by meteorite bombardments left us with those left-handed protein units.

“These meteorites were bringing in what I call the ‘seeds of chirality,'” stated Breslow. “If you have a universe that was just the mirror image of the one we know about, then in fact, presumably it would have right-handed amino acids. That’s why I’m only half kidding when I say there is a guy on the other side of the universe with his heart on the right hand side.”

These amino acids “seeds” formed in interstellar space, possibly on asteroids as they careened through space. At the outset, they have equal amounts of left and right-handed amino acids. But as these rocks soar past neutron stars, their light rays trigger the selective destruction of one form of amino acid. The stars emit circularly polarized light–in one direction, its rays are polarized to the right. 180 degrees in the other direction, the star emits left-polarized light.

All earthbound meteors catch an excess of one of the two polarized rays. Breslow said that previous experiments confirmed that circularly polarized light selectively destroys one chiral form of amino acids over the other. The end result is a five to ten percent excess of one form, in this case, L-amino acids. Evidence of this left-handed excess was found on the surfaces of these meteorites, which have crashed into Earth even within the last hundred years, landing in Australia and Tennessee.

Breslow simulated what occurred after the dust settled following a meteor bombardment, when the amino acids on the meteor mixed with the primordial soup. Under “credible prebiotic conditions”– desert-like temperatures and a little bit of water — he exposed amino acid chemical precursors to those amino acids found on meteorites.

Breslow and Columbia chemistry grad student Mindy Levine found that these cosmic amino acids could directly transfer their chirality to simple amino acids found in living things. Thus far, Breslow’s team is the first to demonstrate that this kind of handedness transfer is possible under these conditions.

On the prebiotic Earth, this transfer left a slight excess of left-handed amino acids, Breslow said. His next experiment replicated the chemistry that led to the amplification and eventual dominance of left-handed amino acids. He started with a five percent excess of one form of amino acid in water and dissolved it.

Breslow found that the left and right-handed amino acids would bind together as they crystallized from water. The left-right bound amino acids left the solution as water evaporated, leaving behind increasing amounts of the left-amino acid in solution. Eventually, the amino acid in excess became ubiquitous as it was used selectively by living organisms.

Other theories have been put forth to explain the dominance of L-amino acids. One, for instance, suggests polarized light from neutron stars traveled all the way to earth to “zap” right-handed amino acids directly. “But the evidence that these materials are being formed out there and brought to us on meteorites is overwhelming,” said Breslow.

The steps afterward that led towards the genesis of life are shrouded in mystery. Breslow hopes to shine more light on prebiotic Earth as he turns his attention to nucleic acids, the chemical units of DNA and its more primitive cousin RNA.

“This work is related to the probability that there is life somewhere else,” said Breslow. “Everything that is going on on Earth occurred because the meteorites happened to land here. But they are obviously landing in other places. If there is another planet that has the water and all of the things that are needed for life, you should be able to get the same process rolling.”

Fragment of the Murchison meteorite (at right) and isolated individual particles (shown in the test tube). (Credit: DOE/Argonne National Laboratory)

 

 

 

Arizona State University — An important discovery was made with respect to the mystery of “handedness” in biomolecules. Researchers led by Sandra Pizzarello, a research professor at Arizona State University, found that some of the possible abiotic precursors to the origin of life on Earth have been shown to carry “handedness” in a larger number than previously thought.

Pizzarello, in ASU’s Department of Chemistry and Biochemistry, worked with Yongsong Huang and Marcelo Alexandre, of Brown University, in studying the organic materials of a special group of meteorites that contain among a variety of compounds, amino acids that have identical counterparts in terrestrial biomolecules. These meteorites are fragments of asteroids that are about the same age as the solar system (roughly 4.5 billion years.)

Scientists have long known that most compounds in living things exist in mirror-image forms. The two forms are like hands; one is a mirror reflection of the other. They are different, cannot be superimposed, yet identical in their parts.

When scientists synthesize these molecules in the laboratory, half of a sample turns out to be “left-handed” and the other half “right-handed.” But amino acids, which are the building blocks of terrestrial proteins, are all “left-handed,” while the sugars of DNA and RNA are “right-handed.” The mystery as to why this is the case, “parallels in many of its queries those that surround the origin of life,” said Pizzarello.

Years ago Pizzarello and ASU professor emeritus John Cronin analyzed amino acids from the Murchison meteorite (which landed in Australia in 1969) that were unknown on Earth, hence solving the problem of any contamination. They discovered a preponderance of “left-handed” amino acids over their “right-handed” form.

“The findings of Cronin and Pizzarello were probably the first demonstration that there may be natural processes in the cosmos that generate a preferred amino acid handedness,” Jeffrey Bada of the Scripps Institution of Oceanography, La Jolla, Calif., said at the time.

The new PNAS work* was made possible by the finding in Antarctica of an exceptionally pristine meteorite. Antarctic ices are good “curators” of meteorites. After a meteorite falls — and meteorites have been falling throughout the history of Earth — it is quickly covered by snow and buried in the ice. Because these ices are in constant motion, when they come to a mountain, they will flow over the hill and bring meteorites to the surface.

“Thanks to the pristine nature of this meteorite, we were able to demonstrate that other extraterrestrial amino acids carry the left-handed excesses in meteorites and, above all, that these excesses appear to signify that their precursor molecules, the aldehydes, also carried such excesses,” Pizzarello said. “In other words, a molecular trait that defines life seems to have broader distribution as well as a long cosmic lineage.””

This study may provide an important clue to the origin of molecular asymmetry,” added Brown associate professor and co-author Huang.

*The work was published in the Early Edition of the Proceedings of the National Academy of Sciences. The paper is titled, “Molecular asymmetry in extraterrestrial chemistry: Insights from a pristine meteorite,” and is co-authored by Pizzarello, Huang and  Alexandre.

Biochemist David Deamer has been studying the origins of life for more than 20 years.

 (Credit: Image courtesy of University of California – Santa Cruz)

 

 

 

University of California – Santa Cruz  —  Researchers in the field of synthetic biology are still a long way from being able to assemble living cells from scratch in the laboratory. But according to biochemist David Deamer of the University of California, Santa Cruz, their efforts are yielding clues to the mystery of how life began on Earth.

Deamer has been investigating the origin of life for more than 20 years, focusing on the molecular self-assembly processes that led to the first “protocells” nearly 4 billion years ago. At the annual meeting of the American Association for the Advancement of Science (AAAS) over a year ago, he discussed evolution, biochemistry, and the origin of cellular life. His presentation was part of a symposium on evolution organized by Eugenie Scott, director of the National Center for Science Education in Oakland, Calif.

According to Deamer, life began with complex systems of molecules that came together through the self-assembly of nonliving components. A useful metaphor for understanding how this came about, he said, can be found in combinatorial chemistry, an approach in which thousands of experiments are carried out in parallel by robotic devices.

“I look at the origin of life as the result of combinatorial chemistry on a global scale,” said Deamer, a research professor of chemistry and biochemistry at UCSC who is also affiliated with the Department of Biomolecular Engineering in UCSC’s Jack Baskin School of Engineering.

The power of combinatorial chemistry lies in the vast numbers of structurally distinct molecules that can be synthesized and tested at the same time. Similarly, conditions on the early Earth allowed not only the synthesis of a wide variety of complex organic molecules, but also the formation of membrane-bound compartments that would have encapsulated different combinations of molecules.

“We have made protocells in the lab–artificial compartments containing complex systems of molecules,” Deamer said. “The creationists charge that it’s too unlikely for the right combination to have come together on its own, but combinatorial chemistry gives us a better way to think about the probability of life emerging from this process.”

Life began when one or a few protocells happened to have a mix of components that could capture energy and nutrients from the environment and use them to grow and reproduce. Efforts to replicate this process in the laboratory are still in their infancy, but Deamer said he is optimistic that scientists will eventually be able to assemble a living cell from a parts list and thereby achieve a better understanding of how life began.

The first forms of life did not evolve in the usual sense, he said, but simply grew. “Evolution began when large populations of cells had variations that led to different metabolic efficiencies,” Deamer said. “If the populations were in a confined environment, at some point they would begin to compete for limited resources.”

The first evolutionary selection processes would have favored those organisms that were most efficient in capturing energy and nutrients from the local environment, he said.

In his talk at the AAAS meeting, Deamer outlined the conditions that scientists think were necessary for life to emerge on the early Earth. He is currently working on a book about the origin of life to be published by UC Press.

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A.J. Hanson – “A construction for computer visualization of certain complex curves”. Amer.Math.Soc and Physics World