A protein that self-replicates

ETH scientists have been able to prove that a protein structure widespread in nature – the amyloid – is theoretically capable of multiplying itself. This makes it a potential predecessor to molecules that are regarded as the building blocks of life.

Lakes in volcanic surroundings could have been the breeding ground for the first biochemical compounds
around 4 to 4.5 billion years ago [Credit: Dhilung Kirat/Wikimedia, ETH Zurich]

Long regarded as a biological aberration, amyloids are fibrous aggregates of short protein fragments. Amyloids have a bad reputation because they are thought to be the cause of multiple neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Creutzfeldt–Jakob disease.

It was only recently that researchers discovered that amyloids appear as structural and functional building blocks in a wide range of life forms, from bacteria, yeast and fungi to humans. In vertebrates, they play a role in the production of the pigment melanin, while yeast cells use amyloid aggregates to form a kind of molecular memory.

Catalysts in prebiotic evolution

Composed of short peptides, amyloid fibres can accelerate chemical reactions in a similar way to enzymes; they have thus been viewed for several years as candidates for the first precursor molecules of life. Until now, however, an important chemical property was lacking in the theory of amyloids role in abiogenesis: self-replication.

Left: electron micrograph of an amyloid fibre. In green is a diagram of the sheet structure characteristic
for amyloids, consisting of multiple short peptide chains [Credit: Jason Greenwald/ETH Zurich]

Early proponents of the amyloid hypothesis include ETH Professor Roland Riek and his senior assistant Jason Greenwald, from the Laboratory of Physical Chemistry. In an experiment, they have now been able to show that amyloids can serve as a chemical template for the synthesis of short peptides. And the critical point: “This ability also potentially applies to the amyloid itself – meaning the molecules can self-replicate,” says Riek. The researchers reported their findings in a study in Nature Communications.

Template for self-replication

The ability to self-replicate is regarded as an essential prerequisite for every early form of life. By proving that amyloids self-replicate, Riek and his team have not only highlighted another amazing aspect of this commonly underestimated protein, but also filled in a previously missing link in the amyloid hypothesis’ argument.

Almost two years earlier, the ETH scientists had already proven in an experiment that amyloid structures can spontaneously form with astounding ease – from simple amino acids that probably already existed when the Earth was still lifeless, and under reaction conditions that appear very plausible for the primordial soup.

The self-replication mechanism of amyloid fibres depicted schematically: piece by piece, specific amino acids (coloured
building blocks) settle at the right site and chemically combine. During the process, the growing amyloid serves
as a template for itself [Credit: Lukas Frey/ETH Zurich]

The same is true for the newly discovered peptide synthesis: “The reaction mechanism seems to be of a general nature. It is stable over a wide range of temperatures and salt concentrations, in both acidic and alkaline environments,” explains Greenwald.

This discovery strengthens the researchers’ opinion that early in evolutionary history, amyloids could have played a central role in the development of early life forms as information carriers and catalytic units.

Not just an RNA world

Until now, however, the most widespread idea for the molecular beginnings of life has been the RNA hypothesis, which sees ribonucleic acid (RNA) as the only key player in the prebiotic primordial soup. This is because, like the genetic material DNA, RNA molecules can code information, and are also able to self-replicate.

The ETH researchers are now picking away at the prevailing dogma of an RNA-based world. They think that the amyloid hypothesis is more plausible; firstly, because RNA molecules with a biological function are much larger and more complex, so they are unlikely to form spontaneously under prebiotic conditions. “Additionally, amyloids are much more stable than early nucleic acid polymers, and they have a much simpler abiotic synthesis route compared to the complexity of known catalytic RNAs,” says Greenwald.

Riek adds: “We will never be able to prove which is true – to do so, we would have to turn back the last 4 to 4.5 billion years of evolution. However, we suspect that it was not one, but multiple molecular processes with various predecessor molecules that were involved in the creation of life.”

Author: Michael Keller | Source: ETH Zurich [February 22, 2018]

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Asteroid 'time capsules' may help explain how life started on Earth

In popular culture, asteroids play the role of apocalyptic threat, get blamed for wiping out the dinosaurs -- and offer an extraterrestrial source for mineral mining.

Credit: Pixabay

But for researcher Nicholas Hud, asteroids play an entirely different role: that of time capsules showing what molecules originally existed in our solar system. Having that information gives scientists the starting point they need to reconstruct the complex pathway that got life started on Earth.

Director of the NSF-NASA Center for Chemical Evolution at the Georgia Institute of Technology, Hud says finding molecules in asteroids provides the strongest evidence that such compounds were present on the Earth before life formed. Knowing what molecules were present helps establish the initial conditions that led to the formation of amino acids and related compounds that, in turn, came together to form peptides, small protein-like molecules that may have kicked off life on this planet.

"We can look to the asteroids to help us understand what chemistry is possible in the universe," said Hud. "It's important for us to study materials from asteroids and meteorites, the smaller versions of asteroids that fall to Earth, to test the validity of our models for how molecules in them could have helped give rise to life. We also need to catalog the molecules from asteroids and meteorites because there might be compounds there that we had not even considered important for starting life."

Hud will be a panelist at a press briefing "Asteroids for Research, Discovery, and Commerce" on February 17 at the 2018 annual meeting of the American Association for the Advancement of Science (AAAS) in Austin, Texas.

NASA scientists have been analyzing compounds found in asteroids and meteorites for decades, and their work provides a solid understanding for what might have been present when the Earth itself was formed, Hud says.

"If you model a prebiotic chemical reaction in the laboratory, scientists can argue about whether or not you had the right starting materials," said Hud. "Detection of a molecule in an asteroid or meteorite is about the only evidence everyone will accept for that molecule being prebiotic. It's something we can really lean on."

The Miller-Urey experiment, conducted in 1952 to simulate conditions believed to have existed on the early Earth, produced more than 20 different amino acids, organic compounds that are the building blocks for peptides. The experiment was kicked off by sparks inside a flask containing water, methane, ammonia and hydrogen, all materials believed to have existed in the atmosphere when the Earth was very young.

Nicolas Hud, director of the NSF-NASA Center for Chemical Evolution at the Georgia Institute of Technology
[Credit: Fitrah Hamid, Georgia Tech]

Since the Miller-Urey experiment, scientists have demonstrated the feasibility of other chemical pathways to amino acids and compounds necessary for life. In Hud's laboratory, for instance, researchers used cycles of alternating wet and dry conditions to create complex organic molecules over time. Under such conditions, amino acids and hydroxy acids, compounds that differ chemically by just a single atom, could have formed short peptides that led to the formation of larger and more complex molecules -- ultimately exhibiting properties that we now associate with biological molecules.

"We now have a really good way to synthesize peptides with amino acids and hydroxy acids working together that could have been common on the early Earth," he said. "Even today, hydroxy acids are found with amino acids in living organisms -- and in some meteorite samples that have been examined."

Hud believes there are many possible ways that the molecules of life could have formed. Life could have gotten started with molecules that are less sophisticated and less efficient than what we see today. Like life itself, these molecules could have evolved over time.

"What we find is that these compounds can form molecules that look a lot like modern peptides, except in the backbone that is holding the units together," said Hud. "The overall structure can be very similar and would be easier to make, though it doesn't have the ability to fold into as complex structures as modern proteins. There is a tradeoff between the simplicity of forming these molecules and how close these molecules are to those found in contemporary life."

Geologists believe the Earth was very different billions of years ago. Instead of continents, there were islands protruding from the oceans. Even the sun was different, producing less light but more cosmic rays -- which could have helped power the protein-forming chemical reactions.

"The islands could have been potential incubators for life, with molecules raining down from the atmosphere," Hud said. "We think the key process that would have allowed these molecules to go to the next stage is a wet-dry cycling like what we are doing in the lab. That would have been perfect for an island out in the ocean."

Rather than a single spark of life, the molecules could have evolved slowly over time in gradual progression that may have taken place at different rates in different locations, perhaps simultaneously. Different components of cells, for example, may have developed separately where conditions favored them before they ultimately came together.

"There is something very special about peptides, nucleic acids, polysaccharides and lipids and their ability to work together to do something they couldn't have done separately," he said. "And there could have been any number of chemical processes on the early Earth that never led to life."

Knowing what conditions were like on the early Earth therefore gives scientists a stronger foundation for hypothesizing what could have taken place, and could offer hints to other pathways that may not have been considered yet.

"There are probably a lot more clues in the asteroids about what molecules were really there," said Hud. "We may not even know what we should be looking for in these asteroids, but by looking at what molecules we find, we can ask different and more questions about how they could have helped get life started."

Source: Georgia Institute of Technology [February 17, 2018]

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