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Origin of life: The chicken-and-egg problem

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Origin of life: The chicken-and-egg problem

A Ludwig-Maximilians-Universitaet (LMU) in Munich team has shown that slight alterations in transfer-RNA molecules (tRNAs) allow them to self-assemble into a functional unit that can replicate information exponentially. tRNAs are key elements in the evolution of early life-forms.

Life as we know it is based on a complex network of interactions, which take place at microscopic scales in biological cells, and involve thousands of distinct molecular species. In our bodies, one fundamental process is repeated countless times every day. In an operation known as replication, proteins duplicate the genetic information encoded in the DNA molecules stored in the cell nucleus — before distributing them equally to the two daughter cells during cell division. The information is then selectively copied (‘transcribed’) into what are called messenger RNA molecules (mRNAs), which direct the synthesis of the many different proteins required by the cell type concerned. A second type of RNA — transfer RNA (tRNA) — plays a central role in the ‘translation’ of mRNAs into proteins. Transfer RNAs act as intermediaries between mRNAs and proteins: they ensure that the amino-acid subunits of which each particular protein consists are put together in the sequence specified by the corresponding mRNA.

How could such a complex interplay between DNA replication and the translation of mRNAs into proteins have arisen when living systems first evolved on the early Earth? We have here a classical example of the chicken-and-the-egg problem: Proteins are required for transcription of the genetic information, but their synthesis itself depends on transcription.

LMU physicists led by Professor Dieter Braun have now demonstrated how this conundrum could have been resolved. They have shown that minor modifications in the structures of modern tRNA molecules permit them to autonomously interact to form a kind of replication module, which is capable of exponentially replicating information. This finding implies that tRNAs — the key intermediaries between transcription and translation in modern cells — could also have been the crucial link between replication and translation in the earliest living systems. It could therefore provide a neat solution to the question of which came first — genetic information or proteins?

Strikingly, in terms of their sequences and overall structure, tRNAs are highly conserved in all three domains of life, i.e. the unicellular Archaea and Bacteria (which lack a cell nucleus) and the Eukaryota (organisms whose cells contain a true nucleus). This fact in itself suggests that tRNAs are among the most ancient molecules in the biosphere.

Like the later steps in the evolution of life, the evolution of replication and translation — and the complex relationship between them — was not the result of a sudden single step. It is better understood as the culmination of an evolutionary journey. “Fundamental phenomena such as self-replication, autocatalysis, self-organization and compartmentalization are likely to have played important roles in these developments,” says Dieter Braun. “And on a more general note, such physical and chemical processes are wholly dependent on the availability of environments that provide non-equilibrium conditions.”

In their experiments, Braun and his colleagues used a set of reciprocally complementary DNA strands modeled on the characteristic form of modern tRNAs. Each was made up of two ‘hairpins’ (so called because each strand could partially pair with itself and form an elongated loop structure), separated by an informational sequence in the middle. Eight such strands can interact via complementary base-pairing to form a complex. Depending on the pairing patterns dictated by the central informational regions, this complex was able to encode a 4-digit binary code.

Each experiment began with a template — an informational structure made up of two types of the central informational sequences that define a binary sequence. This sequence dictated the form of the complementary molecule with which it can interact in the pool of available strands. The researchers went on to demonstrate that the templated binary structure can be repeatedly copied, i.e. amplified, by applying a repeating sequence of temperature fluctuations between warm and cold. “It is therefore conceivable that such a replication mechanism could have taken place on a hydrothermal microsystem on the early Earth,” says Braun. In particular, aqueous solutions trapped in porous rocks on the seafloor would have provided a favorable environment for such reaction cycles, since natural temperature oscillations, generated by convection currents, are known to occur in such settings.

During the copying process, complementary strands (drawn from the pool of molecules) pair up with the informational segment of the template strands. In the course of time, the adjacent hairpins of these strands also pair up to form a stable backbone, and temperature oscillations continue to drive the amplification process. If the temperature is increased for a brief period, the template strands are separated from the newly formed replicate, and both can then serve as template strands in the next round of replication.

The team was able to show that the system is capable of exponential replication. This is an important finding, as it shows that the replication mechanism is particularly resistant to collapse owing to the accumulation of errors. The fact that the structure of the replicator complex itself resembles that of modern tRNAs suggests that early forms of tRNA could have participated in molecular replication processes, before tRNA molecules assumed their modern role in the translation of messenger RNA sequences into proteins. “This link between replication and translation in an early evolutionary scenario could provide a solution to the chicken-and-the-egg problem,” says Alexandra Kühnlein. It could also account for the characteristic form of proto-tRNAs, and elucidate the role of tRNAs before they were co-opted for use in translation.

Laboratory research on the origin of life and the emergence of Darwinian evolution at the level of chemical polymers also has implications for the future of biotechnology. “Our investigations of early forms of molecular replication and our discovery of a link between replication and translation brings us a step closer to the reconstruction of the origin of life,” Braun concludes.

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Mechanism found to determine which memories last

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Origin of life: The chicken-and-egg problem


Neuroscientists have established in recent decades the idea that some of each day’s experiences are converted by the brain into permanent memories during sleep the same night. Now, a new study proposes a mechanism that determines which memories are tagged as important enough to linger in the brain until sleep makes them permanent.

Led by researchers from NYU Grossman School of Medicine, the study revolves around brain cells called neurons that “fire” — or bring about swings in the balance of their positive and negative charges — to transmit electrical signals that encode memories. Large groups of neurons in a brain region called the hippocampus fire together in rhythmic cycles, creating sequences of signals within milliseconds of each other that can encode complex information.

Called “sharp wave-ripples,” these “shouts” to the rest of the brain represent the near-simultaneous firing of 15 percent of hippocampal neurons, and are named for the shape they take when their activity is captured by electrodes and recorded on a graph.

While past studies had linked ripples with memory formation during sleep, the new study, published online in the journal Science on March 28, found that daytime events followed immediately by five to 20 sharp wave-ripples are replayed more during sleep and so consolidated into permanent memories. Events followed by very few or no sharp wave-ripples failed to form lasting memories.

“Our study finds that sharp wave-ripples are the physiological mechanism used by the brain to ‘decide’ what to keep and what to discard,” said senior study author György Buzsáki, MD, PhD, the Biggs Professor of Neuroscience in the Department of Neuroscience and Physiology at NYU Langone Health.

Walk and Pause

The new study is based on a known pattern: mammals including humans experience the world for a few moments, then pause, then experience a little more, then pause again. After we pay attention to something, say the study authors, brain computation often switches into an “idle” re-assessment mode. Such momentary pauses occur throughout the day, but the longest idling periods occur during sleep.

Buzsaki and colleagues had previously established that no sharp wave-ripples occur as we actively explore sensory information or move, but only during the idle pauses before or after. The current study found that sharp wave-ripples represent the natural tagging mechanism during such pauses after waking experiences, with the tagged neuronal patterns reactivated during post-task sleep.

Importantly, sharp wave-ripples are known to be made up the firing of hippocampal “place cells” in a specific order that encodes every room we enter, and each arm of a maze entered by a mouse. For memories that are remembered, those same cells fire at high speed, as we sleep, “playing back the recorded event thousands times per night.” The process strengthens the connections between the cells involved.

For the current study, successive maze runs by study mice were tracked via electrodes by populations of hippocampal cells that constantly changed over time despite recording very similar experiences. This revealed for the first time the maze runs during which ripples occurred during waking pauses, and then were replayed during sleep.

Sharp wave-ripples were typically recorded when a mouse paused to enjoy a sugary treat after each maze run. The consumption of the reward, say the authors, prepared the brain to switch from an exploratory to an idle pattern so that sharp wave-ripples could occur.

Using dual-sided silicon probes, the research team was able to record up to 500 neurons simultaneously in the hippocampus of animals during maze runs. This in turn created a challenge because data becomes exceedingly complex the more neurons are independently recorded. To gain an intuitive understanding of the data, visualize neuronal activity, and form hypotheses, the team successfully reduced the number of dimensions in the data, in some ways like converting a three-dimensional image into a flat one, and without losing the data’s integrity.

“We worked to take the external world out of the equation, and looked at the mechanisms by which the mammalian brain innately and subconsciously tags some memories to become permanent,” said first author Wannan (Winnie) Yang, PhD, a graduate student in Buzsáki’s lab. “Why such a system evolved is still a mystery, but future research may reveal devices or therapies that can adjust sharp wave-ripples to improve memory, or even lessen recall of traumatic events.”

Along with Drs. Buzsáki and Yang, study authors from the Neuroscience Institute at NYU Langone Health were Roman Huszár and Thomas Hainmueller. Kirill Kiselev of the Center for Neural Science at New York University was also an author, as was Chen Sun of Mila, the Quebec Artificial Intelligence Institute, in Montréal. The work was supported by National Institute of Health grants R01MH122391 and U19NS107616.



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Long-period oscillations control the Sun’s differential rotation

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Origin of life: The chicken-and-egg problem


The Sun’s differential rotation pattern has puzzled scientists for decades: while the poles rotate with a period of approximately 34 days, mid-latitudes rotate faster and the equatorial region requires only approximately 24 days for a full rotation. In addition, in past years advances in helioseismology, i.e. probing the solar interior with the help of solar acoustic waves, have established that this rotational profile is nearly constant throughout the entire convection zone. This layer of the Sun stretches from a depth of approximately 200,000 kilometers to the visible solar surface and is home to violent upheavals of hot plasma which play a crucial role in driving solar magnetism and activity.

While theoreticaThe interior of the Sun does not rotate at the same rate at all latitudes. The physical origin of this differential rotation is not fully understood. A team of scientists at the Max Planck Institute for Solar System Research (MPS) in Germany has made a ground-breaking discovery. As the team reports today in the journal Science Advances, the long-period solar oscillations discovered by MPS scientists in 2021 play a crucial role in controlling the Sun’s rotational pattern. The long-period oscillations are analogous to the baroclinically unstable waves in Earth’s atmosphere that shape the weather. In the Sun, these oscillations carry heat from the slightly hotter poles to the slightly cooler equator. To obtain their new results, the scientists interpreted observations from NASA’s Solar Dynamics Observatory using cutting-edge numerical simulations of the solar interior. They found that the difference in temperature between the poles and the equator is about seven degrees.

l models have long postulated a slight temperature difference between solar poles and equator to maintain the Sun’s rotational pattern, it has proven notoriously difficult to measure. After all, observations have to “look through” the background of the Sun’s deep interior which measures up to million degrees in temperature. However, as the researchers from MPS show, it is now possible to determine the temperature difference from the observations of the long-period oscillations of the Sun.

In their analysis of observational data obtained by the Helioseismic and Magnetic Imager (HMI) onboard NASA’s Solar Dynamics Observatory from 2017 to 2021, the scientists turned to global solar oscillations with long periods that can be discerned as swirling motions at the solar surface. Scientists from MPS reported their discovery of these inertial oscillations three years ago. Among these observed modes, the high-latitude modes with velocities of up to 70 km per hour, proved to be especially influential.

To study the nonlinear nature of these high-latitude oscillations, a set of three-dimensional numerical simulations was conducted. In their simulations, the high-latitude oscillations carry heat from the solar poles to the equator, which limits the temperature difference between the Sun’s poles and the equator to less than seven degrees. “This very small temperature difference between the poles and the equator controls the angular momentum balance in the Sun and thus is an important feedback mechanism for the Sun’s global dynamics” says MPS Director Prof. Dr. Laurent Gizon.

In their simulations, the researchers for the first time described the crucial processes in a fully three-dimensional model. Former endeavors had been limited to two-dimensional approaches that assumed the symmetry about the Sun’s rotation axis. “Matching the nonlinear simulations to the observations allowed us to understand the physics of the long-period oscillations and their role in controlling the Sun’s differential rotation,” says MPS postdoc and the lead author of the study, Dr. Yuto Bekki.

The solar high-latitude oscillations are driven by a temperature gradient in a similar way to extratropical cyclones on the Earth. The physics is similar, though the details are different: “In the Sun, the solar pole is about seven degrees hotter than equator and this is enough to drive flows of about 70 kilometers per hour over a large fraction of the Sun. The process is somewhat similar to the driving of cyclones,” says MPS scientist Dr. Robert Cameron.

Probing the physics of the Sun’s deep interior is difficult. This study is important as it shows that the long-period oscillations of the Sun are not only useful probes of the solar interior, but that they play an active role in the way the Sun works. Future work, which will be carried out in the context of the ERC Synergy Grant WHOLESUN and the DFG Collaborative Research Center 1456 Mathematics of Experiments, will be aimed at better understanding the role of these oscillations and their diagnostic potential.



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Artificial reef designed by MIT engineers could protect marine life, reduce storm damage

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Origin of life: The chicken-and-egg problem


The beautiful, gnarled, nooked-and-crannied reefs that surround tropical islands serve as a marine refuge and natural buffer against stormy seas. But as the effects of climate change bleach and break down coral reefs around the world, and extreme weather events become more common, coastal communities are left increasingly vulnerable to frequent flooding and erosion.

An MIT team is now hoping to fortify coastlines with “architected” reefs — sustainable, offshore structures engineered to mimic the wave-buffering effects of natural reefs while also providing pockets for fish and other marine life.

The team’s reef design centers on a cylindrical structure surrounded by four rudder-like slats. The engineers found that when this structure stands up against a wave, it efficiently breaks the wave into turbulent jets that ultimately dissipate most of the wave’s total energy. The team has calculated that the new design could reduce as much wave energy as existing artificial reefs, using 10 times less material.

The researchers plan to fabricate each cylindrical structure from sustainable cement, which they would mold in a pattern of “voxels” that could be automatically assembled, and would provide pockets for fish to explore and other marine life to settle in. The cylinders could be connected to form a long, semipermeable wall, which the engineers could erect along a coastline, about half a mile from shore. Based on the team’s initial experiments with lab-scale prototypes, the architected reef could reduce the energy of incoming waves by more than 95 percent.

“This would be like a long wave-breaker,” says Michael Triantafyllou, the Henry L. and Grace Doherty Professor in Ocean Science and Engineering in the Department of Mechanical Engineering. “If waves are 6 meters high coming toward this reef structure, they would be ultimately less than a meter high on the other side. So, this kills the impact of the waves, which could prevent erosion and flooding.”

Details of the architected reef design are reported today in a study appearing in the open-access journal PNAS Nexus. Triantafyllou’s MIT co-authors are Edvard Ronglan SM ’23; graduate students Alfonso Parra Rubio, Jose del Auila Ferrandis, and Erik Strand; research scientists Patricia Maria Stathatou and Carolina Bastidas; and Professor Neil Gershenfeld, director of the Center for Bits and Atoms; along with Alexis Oliveira Da Silva at the Polytechnic Institute of Paris, Dixia Fan of Westlake University, and Jeffrey Gair Jr. of Scinetics, Inc.

Leveraging turbulence

Some regions have already erected artificial reefs to protect their coastlines from encroaching storms. These structures are typically sunken ships, retired oil and gas platforms, and even assembled configurations of concrete, metal, tires, and stones. However, there’s variability in the types of artificial reefs that are currently in place, and no standard for engineering such structures. What’s more, the designs that are deployed tend to have a low wave dissipation per unit volume of material used. That is, it takes a huge amount of material to break enough wave energy to adequately protect coastal communities.

The MIT team instead looked for ways to engineer an artificial reef that would efficiently dissipate wave energy with less material, while also providing a refuge for fish living along any vulnerable coast.

“Remember, natural coral reefs are only found in tropical waters,” says Triantafyllou, who is director of the MIT Sea Grant. “We cannot have these reefs, for instance, in Massachusetts. But architected reefs don’t depend on temperature, so they can be placed in any water, to protect more coastal areas.”

The new effort is the result of a collaboration between researchers in MIT Sea Grant, who developed the reef structure’s hydrodynamic design, and researchers at the Center for Bits and Atoms (CBA), who worked to make the structure modular and easy to fabricate on location. The team’s architected reef design grew out of two seemingly unrelated problems. CBA researchers were developing ultralight cellular structures for the aerospace industry, while Sea Grant researchers were assessing the performance of blowout preventers in offshore oil structures — cylindrical valves that are used to seal off oil and gas wells and prevent them from leaking.

The team’s tests showed that the structure’s cylindrical arrangement generated a high amount of drag. In other words, the structure appeared to be especially efficient in dissipating high-force flows of oil and gas. They wondered: Could the same arrangement dissipate another type of flow, in ocean waves?

The researchers began to play with the general structure in simulations of water flow, tweaking its dimensions and adding certain elements to see whether and how waves changed as they crashed against each simulated design. This iterative process ultimately landed on an optimized geometry: a vertical cylinder flanked by four long slats, each attached to the cylinder in a way that leaves space for water to flow through the resulting structure. They found this setup essentially breaks up any incoming wave energy, causing parts of the wave-induced flow to spiral to the sides rather than crashing ahead.

“We’re leveraging this turbulence and these powerful jets to ultimately dissipate wave energy,” Ferrandis says.

Standing up to storms

Once the researchers identified an optimal wave-dissipating structure, they fabricated a laboratory-scale version of an architected reef made from a series of the cylindrical structures, which they 3D-printed from plastic. Each test cylinder measured about 1 foot wide and 4 feet tall. They assembled a number of cylinders, each spaced about a foot apart, to form a fence-like structure, which they then lowered into a wave tank at MIT. They then generated waves of various heights and measured them before and after passing through the architected reef.

“We saw the waves reduce substantially, as the reef destroyed their energy,” Triantafyllou says.

The team has also looked into making the structures more porous, and friendly to fish. They found that, rather than making each structure from a solid slab of plastic, they could use a more affordable and sustainable type of cement.

“We’ve worked with biologists to test the cement we intend to use, and it’s benign to fish, and ready to go,” he adds.

They identified an ideal pattern of “voxels,” or microstructures, that cement could be molded into, in order to fabricate the reefs while creating pockets in which fish could live. This voxel geometry resembles individual egg cartons, stacked end to end, and appears to not affect the structure’s overall wave-dissipating power.

“These voxels still maintain a big drag while allowing fish to move inside,” Ferrandis says.

The team is currently fabricating cement voxel structures and assembling them into a lab-scale architected reef, which they will test under various wave conditions. They envision that the voxel design could be modular, and scalable to any desired size, and easy to transport and install in various offshore locations. “Now we’re simulating actual sea patterns, and testing how these models will perform when we eventually have to deploy them,” says Anjali Sinha, a graduate student at MIT who recently joined the group.

Going forward, the team hopes to work with beach towns in Massachusetts to test the structures on a pilot scale.

“These test structures would not be small,” Triantafyllou emphasizes. “They would be about a mile long, and about 5 meters tall, and would cost something like 6 million dollars per mile. So it’s not cheap. But it could prevent billions of dollars in storm damage. And with climate change, protecting the coasts will become a big issue.”

This work was funded, in part, by the U.S. Defense Advanced Research Projects Agency.



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