Biology LIFE

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Apr 24, 2013
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Another piece in the puzzle:

When Caitlin Cornell looked down her microscope, she saw large bright spots against a black background. They resembled miniature suns, blazing against the backdrop of space. And when Cornell showed the spots to her supervisor, Sarah Keller, a chemist at the University of Washington, “we got really excited,” she recalls. “It was a bit of an ‘Aha!’ moment.” Those spots, she realized, might help address a long-standing puzzle about the origin of life itself.

The cells that make up all living things, despite their endless variations, contain three fundamental elements. There are molecules that encode information and can be copied—DNA and its simpler relative, RNA. There are proteins—workhorse molecules that perform important tasks. And encapsulating them all, there’s a membrane made from fatty acids. Go back far enough in time, before animals and plants and even bacteria existed, and you’d find that the precursor of all life—what scientists call a “protocell”—likely had this same trinity of parts: RNA and proteins, in a membrane. As the physicist Freeman Dyson once said, “Life began with little bags of garbage.”
The bags—the membranes—were crucial. Without something to corral the other molecules, they would all just float away, diffusing into the world and achieving nothing. By concentrating them, membranes transformed an inanimate world of disordered chemicals into one teeming with redwoods and redstarts, elephants and E. coli, humans and hagfish. Life, at its core, is about creating compartments. And that’s much easier and much harder than it might seem.

First, the easy bit. Early cell membranes were built from fatty acids—molecules that look like lollipops, with round heads and long tails. The heads enjoy the company of water; the tails despise it. So, when placed in water, fatty acids self-assemble into hollow spheres, with the water-hating tails pointing inward and the water-loving heads on the surface. These spheres can enclose RNA and proteins, making protocells. Fatty acids, then, can automatically create the compartments that were necessary for life to emerge. It almost seems too good to be true.
And it is, for two reasons. Life first arose in salty oceans, and salt catastrophically destabilizes the fatty-acid spheres. Also, certain ions, including magnesium and iron, cause the spheres to collapse, which is problematic since RNA—another key component of early protocells—requires these ions. How, then, could life possibly have arisen, when the compartments it needs are destroyed by the conditions in which it first emerged, and by the very ingredients it needs to thrive?

Caitlin Cornell and Sarah Keller have an answer to this paradox. They’ve shown that the spheres can withstand both salt and magnesium ions, as long as they’re in the presence of amino acids—the simple molecules that are the building blocks of proteins. The little suns that Cornell saw under her microscope were mixtures of amino acids and fatty acids, holding their spherical shape in the presence of salt.
I find that utterly magical. It means that two of the essential components of life, a protocell’s membrane and its proteins, provided the conditions for each other to exist. By sticking to the fatty acids, the amino acids gave them stability. In turn, the fatty acids concentrated the amino acids, perhaps encouraging them to coalesce into proteins. From the very beginning, these partners were locked in a two-step dance that continued for 3.5 billion years, and helped create all the richness of biology from a starting place of mere chemistry. “I agree completely,” Keller tells me. “It’s completely magical. You need those two parts together.”

“It’s fantastic work,” says Neal Devaraj, of UC San Diego. “Their suggestion that membranes could promote the synthesis of [proteins] is really fascinating.”


 
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The role of sugar-backbone heterogeneity and chimeras in the simultaneous emergence of RNA and DNA

Subhendu Bhowmik & Ramanarayanan Krishnamurthy

Nature Chemistry (2019)

Abstract

Hypotheses of the origins of RNA and DNA are generally centred on the prebiotic synthesis of a pristine system (pre-RNA or RNA), which gives rise to its descendent. However, a lack of specificity in the synthesis of genetic polymers would probably result in chimeric sequences; the roles and fate of such sequences are unknown. Here, we show that chimeras, exemplified by mixed threose nucleic acid (TNA)–RNA and RNA–DNA oligonucleotides, preferentially bind to, and act as templates for, homogeneous TNA, RNA and DNA ligands. The chimeric templates can act as a catalyst that mediates the ligation of oligomers to give homogeneous backbone sequences, and the regeneration of the chimeric templates potentiates a scenario for a possible cross-catalytic cycle with amplification. This process provides a proof-of-principle demonstration of a heterogeneity-to-homogeneity scenario and also gives credence to the idea that DNA could appear concurrently with RNA, instead of being its later descendent.
 
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Scientists studying how life arose from the primordial soup have been too eager to clean up the clutter.

Four billion years ago, the prebiotic Earth was a messy place, a chaotic mélange of diverse starting materials. Even so, certain key molecules still somehow managed to emerge from that chemical mayhem — RNA, DNA and proteins among them. But in the quest to understand how that happened, according to Ramanarayanan Krishnamurthy, a chemist at the Scripps Research Institute in California, researchers have been so myopic in their focus on reactions that generate molecules relevant to the planet’s current inhabitants that they’ve overlooked other possibilities.

“They are trying to impose biology today on prebiotic chemistry,” he said. “But trying to make the final product right from the raw material — it misleads us.”

“We forget the mixture,” he added — and with it, the more circuitous chemical routes that could have potentially led to the same biological outcome, the intermediate stages on the path to life that have since faded without a trace.

It makes sense that experimentalists preferred to keep things clean and direct — to synthesize important compounds like amino acids or nucleotides in bits and pieces, and to think of life as bubbling out of more pristine beginnings. “The feeling was that if you tried to incorporate too much into your system,” said John Sutherland, a chemist at the MRC Laboratory of Molecular Biology in England, “everything would start to degrade and you’d just get a mess.”

But research is beginning to show that starting with the right kind of mess is not only more realistic, but more effective at generating the materials vital to life, while also doing away with problems that have plagued purer systems. “There are times when we have mixtures, rather than just the isolated reactants that people typically use, and we get better results,” said Nicholas Hud, a chemist at the Georgia Institute of Technology. When mixtures are taken into consideration, the emergence of life on Earth in some ways “is not as hard as we might think it is.”


In the most compelling evidence to date, Krishnamurthy and a postdoctoral researcher in his lab, Subhendu Bhowmik, looked at how a system of chimeric RNA-DNA molecules — molecules built from the chemical units of both RNA and DNA — produced pure RNA and pure DNA more easily than systems that started out pure. The work, published today in Nature Chemistry, highlights just how essential a diverse, complex blend of ingredients may have been to life’s earliest evolution.

Bring On the Hybrid Monsters

The narrative that has tantalized origin-of-life researchers for decades is the RNA world scenario: Pure RNA arose within the original prebiotic broth of molecules; the RNA made copies of itself but also later evolved and invented DNA as a more stable partner in replication; peptides joined the dance somewhere along the way. This theory has mainly been bolstered by the discovery that RNA can act both as a genetic material and as a catalyst, meaning it could have performed those roles early in life’s history and handed the baton over to DNA and proteins later on.

But the RNA world isn’t a perfect solution. Perhaps the biggest stumbling block is that there have been serious problems with getting pure RNA to replicate itself sustainably in the laboratory. As a first step toward making a copy of itself, a single strand of RNA can take up complementary nucleotide building blocks from its surroundings and stitch them together. But the paired RNA strands then tend to bind to each other so tightly that they don’t unwind without help, which prevents them from acting as either catalysts or templates for further RNA strands.

“It’s a real challenge,” Sutherland said. “It’s held the field back for a long time.”

But perhaps starting with a jumble of compounds instead of pure RNA alone could fix that, Krishnamurthy thought, after a 2016 experiment involving just such a melting pot yielded unexpected results.

He, Hud and their colleagues had been investigating the properties of a hybrid molecule composed of an assortment of RNA and DNA building blocks, which they dubbed a “chimera” — a nod to the monster from Greek mythology that combined lion, goat and serpent body parts. Such chimeras, they thought, might provide insights into the transition from an RNA world to one that also contained DNA. The researchers found that when the chimeras formed double-stranded complexes, they were less stable than double-stranded complexes of pure RNA or pure DNA. At the time, the team interpreted the surprising finding as an indication of why molecules of pure RNA and pure DNA became nature’s favored medium of genetic inheritance over something more mixed.

But it also got Krishnamurthy thinking: What if the chimeric instability was, instead, secretly beneficial and offered a more natural way to get to a world of pure RNA and pure DNA right out of the gate?

That’s what he and Bhowmik showed in their new study. Because the nucleic acids with mixed backbones formed weaker two-strand systems, they didn’t succumb to the strand separation problem that prevented replication for pure RNA. Moreover, during their replication process, the RNA-DNA chimeras preferentially synthesized strands of pure RNA and pure DNA rather than new chimeric molecules — and they produced more of those pure compounds than pure nucleic acid templates did.

There was no need to cleanly synthesize RNA early on to get the materials that life ended up with. Messy, impure templates didn’t just suffice, they worked better. “If you let the reactions happen in a mixture, they automatically give you the molecules you’re looking for without you actually wanting it,” Krishnamurthy said.

This figure contrasts two theorized mechanisms for the evolution of RNA and DNA as we known them: the RNA World Theory, in which pure molecules of RNA somehow arose from a non-RNA precursor, and the Systems Chemistry Theory, in which hybrid molecules made of RNA and DNA subunits preferentially synthesized pure RNA and DNA.


Such RNA-DNA Frankenstein molecules aren’t just convenient inventions pieced together for the sake of the experiment. While no known living microbe or creature has a chimeric genome, one research team has artificially created E. coli that do. And yeast and other microorganisms have been observed to accidentally make such mixtures, though they have enzymatic systems that eliminate such mistakes.

Krishnamurthy and Bhowmik applied their chimeras-first concept to another system, too, with mixtures of RNA and TNA, an artificial nucleotide often used to model what might have come before the RNA world. The results were the same: The more complicated mixture outperformed the systems of pure RNA or pure TNA. “That means the principle of a mixture giving rise to clean [products] is probably very general,” Krishnamurthy said. “It’s not unique to RNA-DNA.”

The findings, according to Antonio Lazcano Araujo, an origin-of-life researcher at the National Autonomous University of Mexico, demonstrate “the chemical wonderland that must have been available prior to the emergence of the first replication systems” — a chemical wonderland that’s now yielding crucial new insights into how life began.


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Life is, I'm afraid vastly overrated until it's compared to the alternative.

Much new stuff coming out about the Archaea (single cell organisms that ain't bacteria) and the relationship to eukaryocytes (multicellular organisms). Over the last decade Genetics has shown some unexpected commonality of some genes between some Archaea and eukaryotic cells and this study from Yale https://news.yale.edu/2019/09/11/molecular-fossils-help-explain-key-evolutionary-event, they found nuclear localization signals (NLS) in all major branches of the Archaea, including the most ancient groups Microarchaeota and Diapherotrites. These were thought to be only found in Eukaryocytes because they concern signalling from the nucleus and their presence, along with genetic evidence suggests the relationship between the 3 main extant domains looks like this.

First cells evolved into either---> Archaea (many different types but one got a nucleus, complex organelles) -plus a very long time ---> Eukaryocytes
or into ---------------------------->Bacteria
 
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Earliest signs of life: Scientists find microbial remains in ancient rocks

by Isabelle Dubach,

Western Australia's famous 3.5-billion-year-old stromatolites contain microbial remains of some of the earliest life on Earth, UNSW scientists have found. Scientists have found exceptionally preserved microbial remains in some of Earth's oldest rocks in Western Australia—a major advance in the field, offering clues for how life on Earth originated. The UNSW researchers found the organic matter in stromatolites—fossilized microbial structures—from the ancient Dresser Formation in the Pilbara region of Western Australia. The stromatolites have been thought to be of biogenic origin ever since they were discovered in the 1980s. However, despite strong textural evidence, that theory was unproven for nearly four decades, because scientists hadn't been able to show the definitive presence of preserved organic matter remains—until today's publication in Geology.

"This is an exciting discovery—for the first time, we're able to show the world that these stromatolites are definitive evidence for the earliest life on Earth," says lead researcher Dr. Raphael Baumgartner, a research associate of the Australian Centre for Astrobiology in Professor Martin Van Kranendonk's team at UNSW. Professor Van Kranendonk says the discovery is the closest the team have come to a "smoking gun" to prove the existence of such ancient life. "This represents a major advance in our knowledge of these rocks, in the science of early life investigations generally, and—more specifically—in the search for life on Mars. We now have a new target and new methodology to search for ancient life traces," Professor Van Kranendonk says.

Drilling deep, looking closely

Ever since the Dresser Formation was discovered in the 1980, scientists have wondered whether the structures were truly microbial and therefore the earliest signs of life. "Unfortunately, there is a climate of mistrust of textural biosignatures in the research community. Hence, the origin of the stromatolites in the Dresser Formation has been a hotly debated topic," Dr. Baumgartner says. "In this study, I spent a lot of time in the lab, using micro-analytical techniques to look very closely at the rock samples, to prove our theory once and for all."

Stromatolites in the Dresser Formation are usually sourced from the rock surface, and are therefore highly weathered. For this study, the scientists worked with samples that were taken from further down into the rock, below the weathering profile, where the stromatolites are exceptionally well preserved. "Looking at drill core samples allowed us to look at a perfect snapshot of ancient microbial life," Dr. Baumgartner says.

Using a variety of cutting-edge micro-analytical tools and techniques—including high-powered electron microscopy, spectroscopy and isotope analysis—Dr. Baumgartner analyzed the rocks. He found that the stromatolites are essentially composed of pyrite—a mineral also known as 'fool's gold' – that contains organic matter. "The organic matter that we found preserved within pyrite of the stromatolites is exciting—we're looking at exceptionally preserved coherent filaments and strands that are typically remains of microbial biofilms," Dr. Baumgartner says.

The researchers say that such remains have never been observed before in the Dresser Formation, and that actually seeing the evidence down the microscope was incredibly exciting. "I was pretty surprised—we never expected to find this level of evidence before I started this project. I remember the night at the electron microscope where I finally figured out that I was looking at biofilm remains. I think it was around 11pm when I had this 'eureka' moment, and I stayed until three or four o'clock in the morning, just imaging and imaging because I was so excited. I totally lost track of time," Dr. Baumgartner says.

Clues for search for life on Mars

Just over two years ago, Dr. Baumgartner's colleague Tara Djokic, a UNSW Ph.D. candidate, found stromatolites in hot spring deposits in the same region in WA, pushing back the earliest known existence of microbial life on land by 580 million years. "Tara's main findings were these exceptional geyserite deposits that indicate that there have been geysers in this area, and therefore fluid expulsions on exposed land surface," Dr. Baumgartner says. "Her study was focused on the broader geological setting of the paleo-environment—lending support to the theory that life originated on land, rather than in the ocean—whereas my study really went deeper on the finer details of the stromatolite structures from the area."

The scientists say that both studies are helping us answer a central question: where did humanity come from?

"Understanding where life could have emerged is really important in order to understand our ancestry. And from there, it could help us understand where else life could have occurred—for example, where it was kick-started on other planets," Dr. Baumgartner says. Just last month, NASA and European Space Agency (ESA) scientists spent as week in the Pilbara with Martin Van Kranendonk for specialist training in identifying signs of life in these same ancient rocks. It was the first time that Van Kranendonk shared the region's insights with a dedicated team of Mars specialists—a group including the Heads of NASA and ESA Mars 2020 missions. "It is deeply satisfying that Australia's ancient rocks and our scientific know-how is making such a significant contribution to our search for extra-terrestrial life and unlocking the secrets of Mars," says Professor Van Kranendonk.

 
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Chemists map an artificial molecular self-assembly pathway with complexities of life

by University of Tokyo
November 15, 2019



1573890785148.png

Two pathways diverged in a chemical synthesis, and one molecule took them both. Chemists at the University of Tokyo have studied how molecular building blocks can either form a spherical cage or an ultrathin sheet that shows some of the basic properties of a "smart" material that can respond to its environment.

"This molecule is interesting because it builds different structures depending on the conditions when it reaches the bifurcation point of its synthesis," said Professor Shuichi Hiraoka from the Department of Basic Science. Hiraoka's research interests are about how molecules put themselves together, including DNA in living cells or micelles, found in both nature and the cosmetics industry.

The bifurcation point is a "fork in the road" of the chemical synthesis pathway where the same precursor molecules can connect in two different ways to eventually form different final structures. In the present reaction, the precursors take different paths depending on the presence or absence of a third molecule.

The precursor molecules are palladium metal atoms and an organic molecule—1,4-bis(3-pyridyloxy)benzene—made from three rings that can easily swing between an S-shape and C-shape orientation.

The third molecule whose presence or absence influences which path the precursors take is a negatively charged anion molecule (either nitrate or triflate).

In the presence of the anion, the organic molecule takes the C-shape and one at a time, four of those C's link together into two O-rings, locking the anion in a spherical cage. Two palladium atoms latch the four C's together at the top and bottom of the cage.

If the anion is absent, the organic molecule swings into the S-shape and connects together with other S-shaped molecules using the palladium atoms as links. Eventually, they form flat sheets about 4 nanometers thick and up to 5 micrometers in diameter.

However, when researchers add the anion to the completed sheet, the molecules will slowly rearrange themselves into the cage formation.

"The sheet is demonstrating some very primitive qualities of a so-called smart material—one that can sense and respond to its environment. This shift from the micrometer-sized sheets to the nanometer-sized cages is a very dramatic structural change," said Hiraoka.

The research team hopes that their work to understand the fundamental chemical properties of these molecules will lead to the possibility of designing molecules that can self-assemble and independently reorganize depending on environmental conditions.

Paths depend on thermodynamics and kinetics

The sheet and cage formations are more chemically stable in different ways. The cage formation is more thermodynamically stable, meaning it would require energy to move out of that formation. The sheet is more kinetically stable than the cage, meaning the molecules are slow to change position. Researchers are excited to have developed an artificial system that contains the complexities of these different stabilities.

"Complicated natural self-assembly reactions in living systems often have kinetic control," explains Hiraoka.

Proteins in living organisms are usually kinetically trapped to stay in their healthy formations even though it would be more thermodynamically stable to aggregate into useless clumps.

In the artificial system that Hiraoka's research team studied, when the precursor molecules form cages, the molecules stay in that final position because it is the lowest thermodynamic energy arrangement.

"The reaction in the early stage to form the cage is very fast, which tells us that the anion is acting as a kinetic template for the precursors to form the cage," said Hiraoka.

However, the reaction to form the sheet proceeds more slowly and researchers say that the molecules become kinetically trapped in the sheet formation without the presence of the anion to provide a template that pulls them into the cage formation.

Researchers plan to continue studying how the self-assembly pathway is controlled and how to manipulate the influence of the kinetic effect and thermodynamic stability.
 
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First detection of sugars in meteorites gives clues to origin of life

November 19, 2019
by Bill Steigerwald, Nancy Jones, NASA


An international team has found sugars essential to life in meteorites. The new discovery adds to the growing list of biologically important compounds that have been found in meteorites, supporting the hypothesis that chemical reactions in asteroids—the parent bodies of many meteorites—can make some of life's ingredients. If correct, meteorite bombardment on ancient Earth may have assisted the origin of life with a supply of life's building blocks.

The team discovered ribose and other bio-essential sugars including arabinose and xylose in two different meteorites that are rich in carbon, NWA 801 (type CR2) and Murchison (type CM2). Ribose is a crucial component of RNA (ribonucleic acid). In much of modern life, RNA serves as a messenger molecule, copying genetic instructions from the DNA molecule (deoxyribonucleic acid) and delivering them to molecular factories within the cell called ribosomes that read the RNA to build specific proteins needed to carry out life processes.

"Other important building blocks of life have been found in meteorites previously, including amino acids (components of proteins) and nucleobases (components of DNA and RNA), but sugars have been a missing piece among the major building blocks of life," said Yoshihiro Furukawa of Tohoku University, Japan, lead author of the study published in the Proceedings of the National Academy of Sciences November 18. "The research provides the first direct evidence of ribose in space and the delivery of the sugar to Earth. The extraterrestrial sugar might have contributed to the formation of RNA on the prebiotic Earth which possibly led to the origin of life."

"It is remarkable that a molecule as fragile as ribose could be detected in such ancient material," said Jason Dworkin, a co-author of the study at NASA's Goddard Space Flight Center in Greenbelt, Maryland. "These results will help guide our analyses of pristine samples from primitive asteroids Ryugu and Bennu, to be returned by the Japan Aerospace Exploration Agency's Hayabusa2 and NASA's OSIRIS-REx spacecraft."

An enduring mystery regarding the origin of life is how biology could have arisen from non-biological chemical processes. DNA is the template for life, carrying the instructions for how to build and operate a living organism. However, RNA also carries information, and many researchers think it evolved first and was later replaced by DNA. This is because RNA molecules have capabilities that DNA lacks. RNA can make copies of itself without "help" from other molecules, and it can also initiate or speed up chemical reactions as a catalyst. The new work gives some evidence to support the possibility that RNA coordinated the machinery of life before DNA.

"The sugar in DNA (2-deoxyribose) was not detected in any of the meteorites analyzed in this study," said Danny Glavin, a co-author of the study at NASA Goddard. "This is important since there could have been a delivery bias of extraterrestrial ribose to the early Earth which is consistent with the hypothesis that RNA evolved first."

The team discovered the sugars by analyzing powdered samples of the meteorites using gas chromatography mass spectrometry, which sorts and identifies molecules by their mass and electric charge. They found that the abundances of ribose and the other sugars ranged from 2.3 to 11 parts per billion in NWA 801 and from 6.7 to 180 parts per billion in Murchison.

Since Earth is awash with life, the team had to consider the possibility that the sugars in the meteorites simply came from contamination by terrestrial life. Multiple lines of evidence indicate contamination is unlikely, including isotope analysis. Isotopes are versions of an element with different mass due to the number of neutrons in the atomic nucleus. For example, life on Earth prefers to use the lighter variety of carbon (12C) over the heavier version (13C). However, the carbon in the meteorite sugars was significantly enriched in the heavy 13C, beyond the amount seen in terrestrial biology, supporting the conclusion that it came from space.

The team plans to analyze more meteorites to get a better idea of the abundance of the extraterrestrial sugars. They also plan to see if the extraterrestrial sugar molecules have a left-handed or right-handed bias. Some molecules come in two varieties that are mirror images of each other, like your hands. On Earth, life uses left-handed amino acids and right-handed sugars. Since it's possible that the opposite would work fine—right-handed amino acids and left-handed sugars—scientists want to know where this preference came from. If some process in asteroids favors the production of one variety over the other, then maybe the supply from space via meteorite impacts made that variety more abundant on ancient Earth, which made it more likely that life would end up using it.

 
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Okay, now THIS is exciting.

1579257754737.png

Depiction of C. reinhardtii life cycles following evolution with (B2, B5) or without (K1) predators for 50 weeks. Categories (AD) show a variety of life cycle characteristics, from unicellular to various multicellular forms. Briefly, A shows the ancestral, wild-type life cycle; in B this is modified with cells embedded in an extracellular matrix; C is similar to B but forms much larger multicellular structures; while D shows a fully multicellular life cycle in which multicellular clusters release multicellular propagules. Evolved strains were qualitatively categorized based on growth during 72-hour time-lapse videos. Strains within each life cycle category are listed below illustrations. Representative microscopic images of each life cycle category are at the bottom (Depicted strain in boldface).

 
Snake,
Have you seen this - Yeasts & Ecoli living in 100% hydrogen Surprising study finds microbes can survive in all-hydrogen atmosphere

Why hasn't anyone tried this before? It's not limited by technology. Conceptual limitations, probably had to wait until all the weirdo 'extremophile' bacteria with unconventional metabolisms were discovered. Importantly these are 'normal' organisms representing 2 different domains. What have so called xenobiologists been doing? Bet there is a swag of experiments with all sorts of critters in different atmospheres, pressures and temperatures that represent potential alien environments. Has anyone tried it with a Mars analogue atmosphere? - Quick trip to Prof Google says yes - https://www.ncbi.nlm.nih.gov/pubmed/23289858/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876496/#B20
 
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