In the molecular dance that gave birth to life on Earth, RNA appears to be a central player. But the origins of the molecule, which can store genetic information as DNA does and speed chemical reactions as proteins do, remain a mystery. Now, a team of researchers has shown for the first time that a set of simple starting materials, which were likely present on early Earth, can produce all four of RNA’s chemical building blocks.

Those building blocks—cytosine, uracil, adenine, and guanine—have  previously been re-created in the lab from other starting materials. In  2009, chemists led by John Sutherland at the University of Cambridge in the United Kingdom devised a set of five compounds likely present on early Earth that could give rise to cytosine and uracil, collectively known as pyrimidines. Then, 2 years ago, researchers led by Thomas Carell, a chemist at Ludwig Maximilian University in Munich, Germany, reported that his team had an equally easy way to form adenine and guanine, the building blocks known as purines. But the two sets of chemical reactions were different. No one knew how the conditions for making both pairs of building blocks could have occurred in the same place at the same time.

Now, Carell says he may have the answer.  On Tuesday, at the Origins of Life Workshop here, he reported that he and his colleagues have come up with a simple set of reactions that could have given rise to all four RNA bases.

Ingredients regarded as crucial for the origin of life on Earth have been discovered at the comet that ESA’s Rosetta spacecraft has been probing for almost two years.

They include the amino acid glycine, which is commonly found in proteins, and phosphorus, a key component of DNA and cell membranes.

Scientists have long debated the important possibility that water and organic molecules were brought by asteroids and comets to the young Earth after it cooled following its formation, providing some of the key building blocks for the emergence of life.

While some comets and asteroids are already known to have water with a composition like that of Earth’s oceans, Rosetta found a significant difference at its comet – fuelling the debate on their role in the origin of Earth’s water.

But new results reveal that comets nevertheless had the potential to deliver ingredients critical to establish life as we know it.

Rosetta’s comet contains ingredients for life

Amino acids are biologically important organic compounds containing carbon, oxygen, hydrogen and nitrogen, and form the basis of proteins.

Hints of the simplest amino acid, glycine, were found in samples returned to Earth in 2006 from Comet Wild-2 by NASA’s Stardust mission. However, possible terrestrial contamination of the dust samples made the analysis extremely difficult.

Now, Rosetta has made direct, repeated detections of glycine in the fuzzy atmosphere or ‘coma’ of its comet. (...)

How can life originate from a lifeless chemical soup? This question has puzzled scientists since Darwin's 'Origin of species'. University of Groningen chemistry professor Sijbren Otto studies 'chemical evolution' to see if self-organization and autocatalysis will provide the answer. His research group previously developed self-replicating molecules—molecules that can make copies of themselves—and have now observed diversification in replicator mutants. They found that if you start with one ancestral set of replicator mutants, a second set will branch off spontaneously. This means that ecological diversity as encountered in biology may well have its roots at the molecular level. The results were published on Jan. 4, 2016, in Nature Chemistry.

Life must have started at some point, but how remains a mystery. Charles Darwin himself speculated in a letter to Joseph Hooker in 1871: 'But if (and oh what a big if) we could conceive in some warm little pond with all sorts of ammonia and phosphoric salts,—light, heat, electricity & c. present, that a protein compound was chemically formed, ready to undergo still more complex changes, at the present day such matter wd be instantly devoured, or absorbed, which would not have been the case before living creatures were formed.'

It is impossible to know how life on Earth really started, but that doesn't stop scientists from trying to find out how it could have started. This is not just a matter of curiosity. The processes involved include autocatalysis (where molecules promote the formation of copies of themselves) and self-organization (where molecules spontaneously organize themselves into higher-order structures) which are important concepts in such fields as materials science.

Replicators

Otto has been working on chemical evolution for several years now. 'It started with a chance discovery', he explains. 'We found some small peptides that could arrange themselves into rings, which could then form stacks.' Once a stack began to form, it would continue to grow and would then multiply by breaking into two smaller stacks. These would both grow and break again, and so on. The stacks also stimulated the formation of the rings from which they are composed. The stacks and rings are called 'replicators', as they are able to make copies of themselves.

Jan Sadownik, a postdoc in the Otto group, discovered that if you offer the replicators two different types (A and B) of building blocks ('food') they will make copies of themselves. He observed the emergence of a set of replicator mutants that specialized in food A, but also incorporated some B. The rings mainly comprised the A building blocks, with just a few B's.

Some days later Sadownik saw a second set of mutants emerge that specialized in food B, but also tolerated some A. This second set proved to be a descendant of the first set, which meant there was an ancestral relationship between the sets. This is very similar to how new species form from existing ones during biological evolution, except that this process of species formation does not involve full-fledged biological organisms, but occurs instead at the molecular level. (...)

(...) After the first touchdown at Agilkia, the gas-sniffing instruments Ptolemy and COSAC analyzed samples entering the lander and determined the chemical composition of the comet’s gas and dust, important tracers of the raw materials present in the early solar system.

COSAC analyzed samples entering tubes at the bottom of the lander kicked up during the first touchdown, dominated by the volatile ingredients of ice-poor dust grains. This revealed a suite of 16 organic compounds comprising numerous carbon and nitrogen-rich compounds, including four compounds — methyl isocyanate, acetone, propionaldehyde and acetamide — that have never before been detected in comets.

Meanwhile, Ptolemy sampled ambient gas entering tubes at the top of the lander and detected the main components of coma gases — water vapour, carbon monoxide, and carbon dioxide, along with smaller amounts of carbon-bearing organic compounds, including formaldehyde.

Importantly, some of these compounds detected by Ptolemy and COSAC play a key role in the prebiotic synthesis of amino acids, sugars, and nucleobases — the ingredients for life. For example, formaldehyde is implicated in the formation of ribose, which ultimately features in molecules like DNA.

The existence of such complex molecules in a comet, a relic of the early solar system, imply that chemical processes at work during that time could have played a key role in fostering the formation of prebiotic material. (...)

Mimicking natural evolution in a test tube, scientists at The Scripps Research Institute (TSRI) have devised an enzyme with a unique property that might have been crucial to the origin of life on Earth.

Aside from illuminating one possible path for life's beginnings, the achievement is likely to yield a powerful tool for evolving new and useful molecules.

"When I start to tell people about this, they sometimes wonder if we're merely suggesting the possibility of such an enzyme—but no, we actually made it," said Gerald F. Joyce, professor in TSRI's Departments of Chemistry and Cell and Molecular Biology and director of the Genomics Institute of the Novartis Research Foundation.

Joyce was the senior author of the new report, which was published online ahead of print by the journal Nature on October 29, 2014.

The Challenge of Making Copies

The new enzyme is called a ribozyme because it is made from ribonucleic acid (RNA). Modern DNA-based life forms appear to have evolved from a simpler "RNA world," and many scientists suspect that RNA molecules with enzymatic properties were Earth's first self-replicators.

The new ribozyme works essentially in that way. It helps knit together a "copy" strand of RNA, using an original RNA strand as a reference or "template." However, it doesn't make a copy of a molecule completely identical to itself. Instead it makes a copy of a mirror image of itself—like the left hand to its right—and, in turn, that "left-hand" ribozyme can help make copies of the original.

No one has ever made such "cross-chiral" enzymes before. The emergence of such enzymes in a primordial RNA world—which the new study shows was plausible—could have overcome a key obstacle to the origin of life.

Biology on Earth evolved in such a way that in each class of molecules, one chirality, or handedness, came to predominate. Virtually all RNA, for example, are right-handed and called D-RNA. That structural sameness makes interactions within that class more efficient—just as a handshake is more efficient when it joins two right or two left hands, rather than a left and a right.

"Scientists generally are taught to think that there has to be a common chirality among interacting molecules for biology to work," said Joyce.

It seems likely, however, that simple RNA molecules on the primordial Earth would have consisted of mixes of both right- and left-handed forms. Despite this reasoning, 30 years ago Joyce, then a graduate student, published a paper in Nature showing that self-replicators would have had a tough time evolving in such a mix. Any strand of RNA that gathered stray nucleotides onto itself would eventually have incorporated an RNA nucleotide of the opposite handedness—which would have blocked further assembly of that copy.

"Since then we've all been wondering how RNA replication could have started on the primitive Earth," Joyce said. (...)

Stanley Miller, the chemist whose landmark experiment published in 1953 showed how some of the molecules of life could have formed on a young Earth, left behind boxes of experimental samples that he never analyzed. The first-ever analysis of some of Miller's old samples has revealed another way that important molecules could have formed on early Earth.

The study discovered a path from simple to complex compounds amid Earth's prebiotic soup. More than 4 billion years ago, amino acids could have been attached together, forming peptides. These peptides ultimately may have led to the proteins and enzymes necessary for life's biochemistry, as we know it.

In the new study, scientists analyzed samples from an experiment Miller performed in 1958. To the reaction flask, Miller added a chemical that at the time wasn't widely thought to have been available on early Earth. The reaction had successfully formed peptides, the new study found. The new study also successfully replicated the experiment and explained why the reaction works. (...)

Imagination is perhaps the most powerful tool we have for creating the future. The same might be said when it comes to creating the past, especially as it pertains to origin of life. Under what conditions did the energetic processes of life first evolve? That question is the subject of a remarkable perspective piece just published in Science. Authors William Martin, Filipa Sousa, and Nick Lane come to the startling conclusion that the energy-harvesting system in ancient microbes can best be understood if it is viewed a microcosm of the larger-scale geochemical processes of the day. In particular, they imagine a process by which natural ion gradients in alkaline hydrothermal vents, much like the "Lost City" ecosystem still active in the mid-Atlantic today, ignited the ongoing chemical reaction of life.

When it comes to origin of life discussions the so-called "RNA World" often comes to mind. While fascinating, that set of ideas is not what is under discussion here. According to the authors, it's all about the acetogens, the methanogens, and the chemical transformations that were key to their evolution. These microorganisms synthesize ATP using electrons from H+ to reduce CO2. In the process they generate either acetate or methane. The shared backbone in the energy metabolism of these microorganisms is the most primitive CO2-fixing pathway we know of—the acetyl-coenzyme A pathway. This pathway is generally referred to as the hub of metabolism as is links glycolytic energy production in the cell with oxidative energy production in its endosymbionts, the mitochondria. (...)

A reconstruction of Earth's earliest ocean in the laboratory revealed the spontaneous occurrence of the chemical reactions used by modern cells to synthesize many of the crucial organic molecules of metabolism (bottom pathway). Whether and how the first enzymes adopted the metal-catalyzed reactions described by the scientists remain to be established. Credit: Molecular Systems Biology

The chemical reactions behind the formation of common metabolites in modern organisms could have formed spontaneously in the earth's early oceans, questioning the events thought to have led to the origin of life.

In new research funded by the Wellcome Trust, researchers at the University of Cambridge reconstructed the chemical make-up of the earth's earliest ocean in the laboratory. The team found the spontaneous occurrence of reaction sequences which in modern organisms enable the formation of molecules essential for the synthesis of metabolites such as amino acids, nucleic acids and lipids. These organic molecules are critical for the cellular metabolism seen in all living organisms.

The detection of one of the metabolites, ribose 5-phosphate, in the reaction mixtures is particularly noteworthy, as RNA precursors like this could in theory give rise to RNA molecules that encode information, catalyze chemical reactions and replicate.

It was previously assumed that the complex metabolic reaction sequences, known as metabolic pathways, occurring in modern cells were only possible due to the presence of enzymes. Enzymes are highly complex molecular machines that are thought to have come into existence during the evolution of modern organisms. However, the team's reconstruction reveals that metabolism-like reactions could have occurred naturally in our early oceans, before the first organisms evolved.

Almost 4 billion years ago life on Earth began in iron-rich oceans that dominated the surface of the planet. This was an oxygen-free world, pre-dating photosynthesis, when the redox state of iron was different and much more soluble to act as potential catalysts. In the Archean sea, iron, other metals and phosphate, facilitated a series of reactions which resemble the core of cellular metabolism occurring in the absence of enzymes.

The findings suggests that metabolism predates the origin of life and evolved through the chemical conditions that prevailed in the worlds earliest oceans.

"Our results show that reaction sequences that resemble two essential reaction cascades of metabolism, glycolysis and the pentose-phosphate pathways, could have occurred spontaneously in the earth's ancient oceans," says Dr. Markus Ralser at the Department of Biochemistry at the University of Cambridge and the National Institute for Medical Research, who led the study.

"In our reconstructed version of the ancient Archean ocean, these metabolic reactions were particularly sensitive to the presence of ferrous iron which was abundant in the early oceans, and accelerated many of the chemical reactions that we observe. We were surprised by how specific these reactions were" he added. (...)