Sunday, December 21, 2014

Abiogenesis - How Life Began

What do we know about how life began?

We're close to revealing the whole story. And - to use the cliche - it's a doozy.

We know life emerged through chemistry - the natural behavior of matter. And that natural behavior includes spontaneous self-assembly, growth, feeding, information storage, replication and evolution - all compelled by simple mechanical and chemical forces. How do we know? Well, we can prove it.

The chemical precursors for life are derived from the universe's most abundant elements: hydrogen, carbon, nitrogen, oxygen, phosphorus and sulphur. These six elements constitute 99% of all matter in living organisms. All were originally forged, no less, in the furnaces of stars, through a process called stellar nucleosynthesis:

These elements combine - not just on Earth, but throughout the universe - into an infinite variety of complex organic molecules.

Organic molecules are those built around carbon; with four unpaired electrons in its outermost valence (electron orbit) shell, carbon is unique in its versatility -  silicon being the next closest in versatility.

Carbon is a promiscuous element, happily mingling with a wide range of chemical partners, in an infinite number of configurations, including rings, sheets, lattices, chains and even tubes.

Among proteins in particular, one finds the most complex configurations known, - organic molecules which bend, fold and twist upon themselves, able to change shape in response to specific chemical stimuli.

But how did we get from such lifeless chemicals to living, breathing, eating, and replicating organisms?Astoundingly, mounting evidence suggests that the process - the emergence of life - is inevitable.

MIT physicist Jeremy England says that thermodynamics predicts life must emerge. Bombarding atoms in an aqueous environment (like an ocean) with external energy like stellar (UV) light, lightning, or volcanic heat causes them to spontaneously restructure to dissipate increasingly more energy. This means, says Dr. England, that given the right conditions, matter is compelled to take on the attributes of living systems by the need to shed energy.

Modern experiments further bolster Dr. England's hypothesis - indicating that not only was our planet able to spontaneously produce life, but under relatively common conditions, the emergence of life may be an inevitability throughout the universe.

Experiments have repeatedly shown that, given an energy source such as heat, stellar (UV) light or electricity, inorganic matter naturally combines to form all the components necessary for life to evolve.

But progressing from non-life to life isn't accomplished in a single step; logically, the emergence of life must have proceeded in four stages:

1) Organic monomers formed - molecular building blocks like nucleobases (RNA and DNA subunits), amino acids (protein subunits), fatty acids (lipid subunits), and monosaccharides (carbohydrate subunits);

2) Organic polymers formed - chains of repeating monomers such as RNA, DNA, proteins, carbohydrates, and lipids;

3) Protective membranes formed around these polymers;

4) Protobionts (lifelike structures) evolved from half a billion years of incremental improvements in survivability - until the emergence of truly living cells, with complex inner functional structures called organelles.

Chemical evolution commenced at some point during stages 1 and 2: just as living organisms do, chemical systems demonstrably compete for chemical resources, until only the most efficient varieties dominate.

Monomer "building blocks" spontaneously form everywhere in the universe, which can then combine into complex chain molecules called polymers.

In the 1920s, Russian biochemist Alexander Oparin was the first to propose that Earth's early ocean chemistry produced these organic polymers, eventually giving rise to life. Dr. Oparin found that stirring fatty oils (lipids) - into water with a wavelike motion created stable membrane-enclosed bubbles he called coacervates. If he added enzymes to the mix and further agitated them, some of these enzymes would become trapped within the coacervates, where they would continue to function.

Coacervates, NASA, 1966. 
Enzymes are special proteins which speed up or otherwise control biochemical reactions upon substrates - the chemicals upon which they act. In an aqueous (water-based) solution, enzyme-containing coacervates will selectively absorb and release specific compounds, much like bacteria feeding and excreting. However, unlike living organisms, simple coacervates are incapable of true complex replication.

The oldest signs of life are some 3.4 billion years old, from the Eoarchean Era, the period after Earth's molten crust first cooled and solidified. It was widely believed the atmosphere at the time consisted mainly of methane, ammonia, water, hydrogen sulfide, carbon dioxide, carbon monoxide and phosphate. The most common forms of molecular oxygen - (O2) and ozone (O3) were likely nearly nonexistent.

This type of atmosphere is said to be reducing (a term from archaic chemistry in which elements appeared to grow lighter from chemical reactions, though the effects are actually caused by a gain of high-energy electrons); experiments show that applying energy to a reducing environment produces an abundant variety of organic monomers:

Using an artificial reducing atmosphere as a model of ancient Earth, graduate student Stanley Miller and professor Harold Urey created a miniature early Earth environment at a University of Chicago lab in 1953. They alternately heated, cooled and applied electricity to a sealed flask of methane, hydrogen, ammonia and water for a week, then tested the contents for signs of organic matter. The results were stunning - the experiment produced many of the most critical organic monomers in great abundance, including 23 different amino acids and formaldehyde, a sugar precursor.

In the intervening six decades, analytical techniques and knowledge of Earth's earliest atmosphere have improved, further solidifying the weight of these findings.

Many variants of the Miller-Urey procedure have since been conducted, producing virtually all the necessary ingredients for life, and showing unmistakeably that, given an energy source and lack of natural barriers, inorganic matter can and does naturally assemble into all the basic components necessary for life. These components include all the monomers for nucleic acids like RNA and DNA, proteins, sugars, fats and oils, as well as the basic chemistry for metabolism - the extraction and use of energy to maintain life.

It all starts with one of the most common compounds in the universe - hydrogen cyanide. While HCN is deadly to aerobic (oxygen-breathing) organisms, it can be used to jumpstart virtually all of life's chemical subsystems.

Exposing HCN or its close cousin ammonium cyanide (NH4CN) to heat or ultraviolet light produces nucleobases - the building blocks of RNA and DNA.

When water reacts with hydrogen cyanide, it creates formamide, another substance found throughout the universe. Heating and exposing formamide to various Earth-based minerals produces all four RNA nucleobases, as well as a number of other organic molecules.

Amazingly, simply freezing ammonia cyanide also forms seven types of amino acids and 11 kinds of nucleobases. This is because, as water freezes, it expands into fixed, orderly crystal lattices, physically lining up compatible monomers into chain molecule patterns which can then bond.

In fact, organic monomers are surprisingly easy to produce: in 1962, Spanish biochemist Joan Oro i Florensa first synthesized the nucleobase adenine simply by leaving ammonium cyanide in standing water. Since then, Oro and many others have synthesized sugars, amino acids, lipids, and two of the five RNA-DNA nucleic acid bases by applying UV radiation (sunlight), heat or electricity to mixtures of methane, ammonia and water.

Florida State biochemist Dr. Sidney W. Fox also found that naturally-occuring environments easily fuse monomers into polymers, although they typically form random sequences: if one leaves amino acids out to dry upon hot clay, sand or rock, they naturally polymerize into peptides - the chain molecules from which proteins are made.

On ancient Earth, ocean waves likely splashed amino acid monomers onto hot rocks or lava, then rinsed the newly-formed peptides back into the sea. With little atmospheric oxygen to break apart those molecular bonds, and no bacteria to cause decay, organic molecules could well have accumulated and filled early Earth's oceans with a thick, warm organic soup for hundreds of millions of years.

Dr. Fox further demonstrated that amino acids in proximity to deep-sea hydrothermal vents will cluster into microspheres, protein globules superficially resembling primitive bacteria in structure.

Many scientists believe deep-sea hydrothermal vents produced the very first life; all the ingredients and conditions necessary for primitive life to emerge would have been - and still are - found in and around such vents. Nobel prizewinner Jack W. Szostak, a Harvard University genetics professor, is among those who are certain life originated from these deep-sea hydrothermal vents, more commonly known as black smokers.

Similar conditions are found in hot mineral springs like those found in Yellowstone National Park. It is in such conditions where stromatolites are found, fossil remains of some of Earth's oldest known life forms.

Under these conditions, molten rock from the earth's mantle sheds hydrogen-rich fluids into carbon dioxide-rich water. As electron-donating hydrogen meets electron-accepting carbon dioxide, it creates perpetual electron exchanges called redox reactions (reduction-oxidation reactions).

These continuous, highly exothermic (energy-releasing) chemical processes provide constant, intense life-feeding and molecule-fusing energy - ideal conditions for producing concentrated organic molecules. Even today, such vents produce million-fold concentrations of organic precursor molecules, and RNA molecules have been found to spontaneously self-assemble in and around them.

In the earliest oceans, those conditions would have been much more pronounced, with a thousand-fold greater concentration of carbon dioxide. Combining this CO2 with tremendous outpourings of methane and hydrogen, deep-sea hydrothermal vents would have provided a constant, dense soup of organic monomers, driven by volcanic heat to combine, undisturbed by chemically disruptive oxygen.

Volcanic regions would have covered much of the Earth, both out of and under the seas, where transient heating and cooling bonded, separated and rebonded nucleic acids and other organic molecules.

Deep-sea vents also emit bubbles of iron and nitrogen sulfides, minerals that contain negatively charged, highly reactive sulfur S2− . These sulfide bubbles create energy-dense, protective membrane-bound sacs which readily trap organic molecules within. Laboratory studies have demonstrated such sulfides also drive the conversion of formate - abundant near sea vents - into nucleobases.

Hydrothermal vents might also have birthed more exotic predecessors of modern organic molecules across ejection zones many kilometers in diameter by ejecting exotic minerals such as zinc and alabandite, which can store UV radiation, providing energy for polymer synthesis.

With no protective ozone layer, UV levels on ancient Earth would have been up to 100 times more intense than today; any "charged" volcanic metals could easily have provided energy to drive the synthesis of organic polymers. Montana State University's Zachary Adam suggests that radioactivity from uranium and other radioactive elements strewn about Earth's first beaches could also have provided energy to synthesize amino acids, sugars, and other organic molecules.

Perhaps the strongest support for the oceanic origin-of-life scenario is the fact that deep hydrothermal vents - which reach temperatures of up to 400 degrees celsius - are still sources of a rich ecosystem built around extremophile microorganisms.

Genetic analyses show the gene sequences of these microorganisms place them at the very base of the tree of life - closest to that of the Last Universal Common Ancestor - the theoretical ancestor of all known life on Earth.

Of course, life cannot function without energy for metabolism.

Metabolism consists of the orderly, cyclical biochemical breakdown (catabolism) and buildup (anabolism) of organic molecules like sugars, proteins, nucleic acids, and lipids. Both processes are concurrent and constant.

Researchers have long been trying to determine how metabolism first evolved. Now, it appears they have found the answer - it arises naturally, given a wide range of favorable conditions.

Highly alkaline (-ion rich) water carries a strong negative charge, and is thus a reducing agent, meaning that it either removes oxygen or adds hydrogen to stabilize molecular charges; conversely, highly acidic (+ion rich) water carries a strong positive charge, and is thus an oxidizing agent, stripping away electrons and adding oxygen or removing hydrogen.

Based upon these principles, the same hydrothermal vents which produce abundant organic molecules also supply abundant metabolic energy. This would have been particularly pronounced when carbon dioxide levels were a thousandfold higher. Black smokers would have provided constant, intense energy by spewing highly alkaline material into oceans made highly acidic by concentrated carbon dioxide, providing a pH gradient - the buildup of opposing electron charges.

Such a pH gradient is precisely the mechanism used by living cells to create and sustain a membrane potential - a built-up charge resulting from a cell's highly alkaline interior separated by a thin membrane from a highly acidic exterior - ions are attracted toward one another across the membrane, thus intensifying the charge, and acting like a natural capacitor that can build up a charge and release it when needed.

To produce life-sustaining energy and structural materials, most living organisms consume carbohydrates, commonly referred to as sugars. These carbohydrates can be monomers like glucose, or polymers like cellulose and chitin. All these carbohydrates share a common chemical formula - molecular "chain links" of CH2O - carbon, hydrogen, oxygen in a ratio of 1:2:1.

Through a series of chemical reactions called cellular respiration, the carbohydrate glucose can be broken down to form adenosine triphosphate (ATP), a "rechargeable molecular battery" used to transport chemical energy within cells.

Temporarily splitting off one phosphate group releases energy to power life-sustaining biological functions, so ATP is continuously broken down and re-constructed to release and store chemical energy.

As mentioned above, cells build up charges against the walls of their membranes to drive life processes. This is the same principle at work in typical store-bought batteries - the natural repulsive and attractive forces between negatively-charged electrons and positively-charged protons creates a kind of electronic pressure called voltage, which can be harnessed to power physical movement or chemical processes.

The buildup of electron charge distributions - a gradient - can be produced by breaking ATP bonds. Thus, ATP is really at the heart of what it means to be "alive".

In 1963, Carl Sagan and colleagues first synthesized ATP by shining ultraviolet light upon water filled with DNA and RNA precursors (adenine, ribose and ethyl metaphosphate) - vital organic molecules called "nucleic acids" because they tend to be concentrated within a cell's nucleus.

But the enzymes required to naturally synthesize and break down ATP may not initially have existed on Earth. Thus early life may have used a special "imported" variety, so to speak. This may have given life a jumpstart: phosphorus - a key element of essential organic molecules, including ATP and DNA, is commonly found on Earth in a nonreactive form - one that doesn't readily combine with other chemicals.

But Dr. Terry Kee at the University of Leeds has found that ATP precursors can be produced by placing meteoric samples into hot acidic pools - such as those which would have covered much of the early Earth. Meteors and interstellar dust constantly bombarded early Earth, seeding it with exotic minerals, including a highly reactive iron-nickel-phosphorus compound called schreibersite.

Dr. Kee incubated meteoric schreibersite in heated test tubes of volcanic acid from Iceland over a period four days, followed by 30 days of cooling at room temperature. The resulting solution was found to contain pyrophosphite, a chemical cousin of ATP, which Dr. Kee believes was an earlier form of that life-sustaining molecule. The energy from pyrophosphite, he contends, could power the formation of ever greater molecular sophistication and complex behaviors, eventually culminating in the first life.

Today, aerobic organisms use one central series of chemical reactions to produce ATP, meaning it is almost certainly one of the first parts of metabolism - and life itself - to have evolved. This is the Krebs Cycle or Citric Acid Cycle. But there are alternative chemical pathways which may have emerged first to power life:

In the 1980s, Drs. Geter Wächtershäuser and Karl R. Popper mapped out possible ancestral metabolic pathways that use iron-sulfur compounds to synthesize organic molecules. Instead of relying upon external sources of energy like UV (sun)light or lightning, their Wächtershäuser systems use built-in energy from redox reactions with mineral sulfides like pyrite.

In this way, the Acetyl-CoA Pathway would have enabled organic chemicals to self-organize upon metal sulfide surfaces, bypassing the need for the Citric Acid Cycle.

Such psuedo "chemical life" systems would have been an intermediate step between inorganic rock and the first living organisms, analagous to machines capable of moving and responding to their environments, while not genuinely alive.

This is not mere speculation, as a class of microbes alive today feed by oxidizing inorganic compounds, including ferrous iron, hydrogen, ammonia or sulfur compounds, a system known as chemolithotrophy. Some of these same prokaryotes are vital for soil fertility.

In 2014, Cambridge University's Markus Ralser demonstrated how the first pseudo organisms could become metabolically active - breaking down nutrients for energy storage or macromolecule assembly. The first steps in the natural transition from simple, inorganic matter into the building blocks of life can be initiated by exposure to common metal ions, which promote the formation of not just metabolic components, but also virtually all the vital monomers, including amino acids, lipids and nucleic acids.

Based upon geological records of ancient ocean sediments, Dr. Ralser and his team reconstructed the chemistry of Earth's four-billion-year-old Archean ocean. At that time, soluble iron had been one of the most abundant molecules in the seas which bathed most of the planet's surface.

Dr. Ralser's team added sugar phosphates - critical for metabolism. They next heated the lab seawater to temperatures like those of hydrothermal vents. While such high temperatures - up to 400°C - quickly destroy modern protein enzymes, they actually promote the formation of life-sustaining metabolites.

Follow-up analyses showed that ferrous iron (iron atoms from which two electrons have been stripped via oxidation) had played a major role in driving 29 separate life-critical chemical reactions related to metabolism.

Among the 29 chemical reactions the research team observed were several which synthesize essential organic molecules, including precursors of lipids, and amino and nucleic acids - necessary for proteins and RNA. Ferrous iron also facilitated the formation of molecules necessary for glycolysis (nutrient-splitting) as well as the pentose-phosphate pathways - two of the most critical and central chemical cascades in metabolism.

Dr. Ralser's experiments produced some of the most important life-sustaining chemical reactions used by modern cells. Prior to these findings, it was believed such reactions required highly-evolved, complex enzymes - proteins which regulate biochemical activity. Surprisingly however, these core reactions could occur without enzymes, instead relying only upon ions present in the ancient Archean sea. In other words, the processes underlying metabolism could naturally develop before life ever evolved.

Of particular note to Dr. Ralser's team was the production of ribose 5-phosphate, critical for RNA synthesis. RNA alone can encode genetic information for replication, and can catalyze life-sustaining chemical reactions.

But a terrestrial "organic soup" may not have been the (only) way life first emerged:

Within the last half-century, many scientists have come to the conclusion that Earth was seeded with the precursors for life from outer space, the process known as panspermia.

Cosmic dust permeating the universe contains complex organic molecules naturally produced in huge quantities by stellar activity. The synthesis of such organic molecules appears to be common among planetary star systems. Thus, the seeds of life may have been organic molecules formed on dust and other particles in the protoplanetary accretion disk surrounding the Sun - matter which was destined to coalesce into our home planet, as well as other members of the solar system.

Progressively heavier elements are produced by generations of supernovae - the apocalyptic explosions of dying stars. Such events, which led to the current structure of the universe, spread heavy elements essential to the formation of life-supporting planets.

In the meantime, as these heavy elements spread, their radiation helped fuse organic molecules in molecular clouds and circumstellar envelopes throughout space. Most of these organic compounds carried by interstellar dust particles are major components required for the function and evolution of living organisms.

This is because three of the most critical organic molecules share essentially the same three-part "recipe":
a 5-carbon sugar, a nitrogen-containing base and a phosphate group. 

These three nucleotide-based molecules include:

1) Adenosine phosphates like ATP, the cellular energy carrier.

2) Coenzymes like NAD+ and related chemicals used in the third stage of cellular respiration - electron transport:

3) Nucleic Acids like RNA and DNA.

Glycolaldehyde - the smallest possible sugar-related molecule - has been found in star dust near the center of the Milky Way and other star systems, suggesting that organic molecules may form in stellar systems prior to planet formation, seeding nascent planets with the precursors for life.

Glycolaldehyde can be used to form RNA; and since sugars are used in both metabolic pathways and genetic code systems - two of the most essential aspects of life - the discovery of sugar outside our planet further increases the probability of extraterrestrial life. NASA astrobiologist Carl Pilcher says these findings strengthen the argument that " in the universe may be common rather than rare."

Recent experiments also show that DNA - and even some living organisms - can survive the conditions of outer space, as well as atmospheric entry to Earth.

Extremophiles - microorganisms which thrive in extremely high-or low-temperature environments - can potentially survive in outer space - and perhaps for a very, very long time: when researchers from the German Aerospace Centre in Cologne mixed bacterial spores with sandstone, then launched them into space for two weeks via Russia's FOTON satellite, nearly all the spores survived.

Even more surprising was the recent finding that cyanobacteria, better known as blue-green algae, had survived for 533 days in space attached to the hull of the International Space Station.

But experiments show bacterial spores embedded in meteorites or comets could survive indefinitely - or at least for hundreds of millions of years - like the spores which survived 30 million years in the abdomen of a bee lodged in amber; or those found embedded for 250 million years in salt crystals from the Permian era.

But life need not have evolved separately on individual planets; perhaps it evolved on one, then spread through the galaxy from star system to star system via comets or meteorites. In other words, the ancestors of all life on earth could have been extraterrestrial microbes.

Meteorites - rocky extraterrestrial fragments which fall to Earth - have been literally and constantly "raining down upon us" since the birth of our planet. Much of this debris burns up due to friction igniting flammable gasses in our atmosphere; however, our planet still accumulates up to a million kg of such space debris every day.

In the end, generally only about 1% is large enough to recover and identify. A special class of them - carbonaceous chondrites - are fragments of asteroids which have remained relatively unchanged since the formation of our solar system 4.6 billion years ago. They contain large quantities of carbon incorporated into organic materials like polycyclic aromatic hydrocarbons (PAHs).

PAHs are the byproducts of stellar and planetary birth, and as such, have existed in great quantities since shortly after the Big Bang. Distributed throughout the universe, they're found in meteorites, comets and even interstellar space. NASA researchers believe as much as 20% of the carbon in the universe may be contained in PAHs, which could act as interstellar seeds for biogenesis. Stellar radiation and temperature fluctuations readily and often transform these PAHs into complex organic molecules, including amino acids and nucleobases.

NASA researchers estimate that during the Late Heavy Bombardment, when the massive gravitational influence of the gas giants Jupiter and Saturn sent asteroids and comets hurtling throughout the inner solar system, comets and meteorites dropped five million tons of organic matter a year upon the Earth's surface; NASA biochemist Loren Williams says this transformed ancient Earth into a "dirty RNA World" where proteins, lipids and RNA could have evolved more or less concurrently.

This scenario seems increasingly likely as the data increases - among the extraterrestrial materials found on meteorites, scientists have detected the nucleobases adenine, guanine and uracil, as well as fatty acids, and 74 different types of amino acids. The amino acid glycine was also detected in the Comet Wild-2 in 2004. In fact, scientists have known since 1971 that comets are key transporters of organic molecules to Earth's early biosphere.

Comets are encrusted with tar-like outer layers of material believed to be composed of complex organic molecules produced when carbon compounds are exposed to ionizing stellar radiation. Rich in carbon and water, they carry a number of organic precursors like amino acids and other hydrocarbons. Together, comets and meteorites rained huge quantities of water and complex organic matter upon Earth - five million tons a year for about one hundred million years.

NASA has said that Saturn's largest moon Titan and Jupiter's moon Europa also harbor complex organic chemicals, but the agency's main focus has shifted to Mars, where multiple lines of chemical evidence suggest the Red Planet may have originally been more favorable than Earth for producing RNA. If this is true, precursor molecules may have been produced on Mars, then travelled to Earth via meteors, seeding our planetary home.

Currently, NASA's prime objective is the search for signs of ancient life on Mars, using the Curiosity and Opportunity rovers. The agency hopes to find evidence of ancient water, or fossilized evidence of autotrophic (self-feeding), chemotrophic (chemical consuming), or chemolithoautotrophic (mineral-converting) microorganisms.

Aside from assembling coherent structures and metabolizing energy, living organisms also need a means of perpetuating their existence through reproduction.

Life's inherent fragility poses a key challenge for survival - loose complex organic molecules have extremely short lifespans, soon deteriorating and breaking down. Because of this, evolution (essentially a very lengthy process of biochemical trial and error) has devised an extremely clever means of sustaining life - using chemicals for data storage - data storage which provides a template for growth and reproduction.

The earliest reproduction was probably just the simple splitting of a growing structure into two or more identical or nearly identical parts, each containing an energy-production and growth system. This may even have been just a simple shaking apart by ocean waves or some other physical disturbance.

However, in our present world, reproduction is provided by sophisticated molecular templates - the nucleic acids RNA and DNA, which carry codes for self-replication and for protein synthesis.

The data for building proteins is contained within specific data regions called genes, linked within the double helix of deoxyribonucleic acid (DNA). These genes are first transcribed into ribonucleic acid (RNA) molecules, then translated into specific amino acid sequences which make up a polypeptide chain.

The polypeptide chain, guided by ionic charges upon its surfaces, then folds into a complex functional structure called a protein. Whether that protein acts as an enzyme controlling biochemical reactions,
a transcription factor regulating protein manufacture, or a structural component depends upon the type and order of amino acids in its polypeptide chain(s). Minor chemical charges carried by these amino acids and the order in which they are strung together determine how each protein's polypeptide chains fold and twist into specific three-dimensional shapes.

Complex molecules can evolve via natural selection - survival of the fittest - just like organisms in nature. The process has been demonstrated repeatedly in the laboratory:

In 1961, American molecular biologist Sol Spiegelman discovered a phage - a bacteria-infecting virus - he called MS2, which functioned entirely upon RNA, without any DNA. Its RNA was also surprisingly simple - consisting of only 218 nucleobases, making it easy to isolate and then synthesize.

Seigelman isolated the the replicase - replicating enzyme - which permitted the virus to copy its RNA, and synthesized it in the laboratory. He then could mass produce many copies of his "little monster" - the viral RNA. He found that, by applying selective pressures (environmental survival challenges), such as temperature or nutrient changes, he could induce the evolution of a wide range of mutant RNA molecules.

Nobel Prize-winning German biochemist Manfred Eigen would follow up on Spiegelman's experiments to produce an even smaller version of Spiegelman's monster: a complete, viable, evolving, organic chemical system containing only 48 nucleotides - essentially material existing between the state of life vs. non-living matter.

But this is the point at which scientists encountered a "stumbling block" in their detective work:

Life evolved from a comparatively simple self-replicating molecular system some 3.8 billion years ago. However, there is a chicken-vs.-egg problem here: nucleic acids are needed to synthesize proteins, and protein enzymes are needed to synthesize nucleic acids. This mutual dependency results in the central paradox regarding origins of life - which came first, nucleic acids or proteins?

DNA and RNA are composed of alternating links of five repeating base molecules strung along an alternating sugar-phosphate backbone. Each base is either a double-ring "purine" (adenine or guanine), or a single-ring "pyrimidine" (thymine, cytosine or uracil); each also attaches to a "pentose" (five-carbon) sugar - either deoxyribose (named for the absence of one oxygen atom) or ribose.

By combining with a phosphate group (a molecule containing one phosphorous and three oxygen atoms) and shedding a water molecule, the bases assemble in chains up to nearly two meters in length. These are protein-assembling blueprints. Thus, RNA and DNA are built up of repeating 3-part monomers, made up of a nucleobase, a ribose sugar and a phosphate group.

The repeating units of ribose sugar and phosphates form a molecular "backbone" upon which the nucleotide bases line up. But free nucleobases must bond to the ribose along this sugar-phosphate backbone, something which has proven difficult to induce spontaneously. All three components easily form under natural conditions, but how they spontaneously combine into longer polymers is still a bit of a mystery. So far, a few possible ways have been demonstrated:

Many organic molecules are synthesized through dehydration synthesis. In this process, removal of a water molecule leaves mutually-attractive molecular free ends which bond. Glycosidic bonds - those between ribose sugars and nucleic acid bases - are formed this way. The problem is that protein enzymes are normally required to drive dehydration synthesis and join momoners into polymers such as proteins, carbohydrates, RNA and lipids. What's more, in ocean water, free-floating monomers will immediately rebond with water, making them unavailable for polymerization.

But Dr. Oro and others have shown that adding cyanamide - a direct product of hydrogen cyanide - triggers nucleotide assembly of bases, sugars and phosphates, just as it assists the polymerization of peptide chains from amino acids. (Polyphosphates - precursors of key organic compounds like ATP - have also been shown to drive amino acid polymerization.)

Recent experiments at the Georgia Institute of Technology also show that simply drying nucleobases can prompt them to spontaneously bond with ribose.

Dr. John Sutherland and colleagues at the University of Cambridge found yet another pathway -  simply heating a mixture of water and organic molecules to the point of evaporation, then irradiating the mixture with ultraviolet light (like that outside Earth's protective ozone layer) assembles organic precursors into RNA. The trick is in the precursors Dr. Sutherland's team uses: naturally-forming intermediates, which spontaneously bond with phosphates under ultraviolet light.

His team also found that ultraviolet radiation converts hydrogen cyanide and certain metals into the sugar building blocks glycolaldehyde and glyceraldehyde. Formaldehyde - found throughout space and especially in the ice of comets - also spontaneously forms sugars - a fact demonstrated as far back as 1861 by the founder of modern chemistry, Alexander Butlerov.

Protein precursors - peptide chains - also spontaneously form given the right conditions, but without nucleic acids, there is no means of storing or transferring instructions for assembling the correct sequences of amino acids into proteins. Thus, it has long been believed that RNA must have been the first organic polymer to evolve.

There are a number of lines of evidence to support this. For example, two central components of RNA - ribose sugar and the nucleobase adenine - are nearly ubiquitous - as part of the most important metabolic chemicals - ATP, NAD, FAD, coenzyme A, cyclic AMP and GTP. These molecular energy carriers all participate in the electron transport chain, a series of chemical electron exchanges (redox reactions) - that ultimately supply living cells with energy.

Metabolism, as we saw, is the sum of all activities in which an organism engages to sustain life. It consists of catabolism - the breakdown of nutrients to provide energy or raw materials for tissue repair and growth
 - and anabolism - the synthesis of macromolecules - mainly proteins for growth and regulatory activities, as well as  polysaccharides (complex sugars) like glycogen (a sugar storage molecule used by animals) and adipose (body fat) for long-term glucose energy storage.

(In the case of plants, that energy storage molecule is starch, or the structural molecule cellulose, and in the case of fungi, insects, crustaceans, molluscs, and cephalopods like squid and octopuses, the structural molecule chitin. Bacteria also produce polysaccharides, usually as protective outer coatings.)

Modern metabolic regulation is much more complex and thus requires specialized enzymes, long thought to only consist of proteins. And proteins, of course, are all built according to blueprints encoded in regions of DNA known as genes, and synthesized by combinations of specialized RNA and additional regulatory proteins. Because of this, evolutionary biochemists are faced with the aforementioned chicken-vs.-egg dilemma: RNA and DNA - nucleic acid - synthesis requires proteins, but protein synthesis requires nucleic acids. You can't have one without the other - or so it was thought.

However, in the early 1980s, Dr. Tomas Cech at the University of Colorado discovered special forms of RNA in living cells which not only store information, but can also function as catalysts (from the Latin for "breaking downward"), substances which promote chemical reactions without being consumed in the process. In living cells, catalysts - usually protein enzymes - drive all life-sustaining processes.

Dr. Cech's discovery meant that primitive life could have been jumpstarted by RNA alone, until the evolution of a more complex form of data-storing nucleic acid - DNA - and more versatile metabolism-controlling protein enzymes.

Dr. Cech called his enzyme-like RNA molecules “ribozymes", to indicate both their structure and function. Capable of both storing information and catalyzing chemical reactions, ribozymes have both basic features necessary for self-replication and evolution.

Dr. Cech would eventually win a Nobel Prize for his discovery, and in the interim, over 500 more ribozymes would be found; since then, RNA has been shown capable of nearly any task performed by proteins.

Remarkably, RNA can tailor itself - removing unwanted nucelotide sequences called "introns". RNA can also synthesize additional forms of RNA, such as specialized messenger RNA, ribosomal RNA, and transfer RNA.

Common montmorillonite clay - used worldwide in the drilling industry - can also guide RNA formation from free nucleotides. Zinc ions in the clay act as a catalyst to polymerize nucleotides into RNA strands.

If supplied with sufficient nucleotides, some RNA can even replicate itself within a test tube: relatively short replicase RNA, has been artificially produced in the lab independently by both Nobel laureate and Harvard geneticist Dr. Jack William Szostak and graduate student Tracey Lincoln at the Scripps Research Institute. This RNA acts as both a genetic storage molecule and a catalyst capable of replication using its own genetic code.

However, the assembly of nucleotides into anything other than molecular gibberish requires guidance. Therefore, it's possible that smaller nucleotide assemblies - pre-RNA polymers - existed first, eventually guiding the assembly of ever more complex molecules. This scenario has been backed up by experiments by Danish molecular biologists like Peter E. Nielsen and Michael Egholm, who showed that shorter, simpler molecules like Peptide Nucleic Acids can be used to assemble RNA and DNA strands. One alternative form of DNA -  Phosphoramidate DNA - can even spontaneous self-assemble.

These simpler alternatives to modern RNA and DNA may have first emerged - nucleic acid analogues like PNA, TNA or GNA - then later evolved into RNA. Instead of relying upon comparatively unstable sugars like ribose, their backbones can be built from peptides or small 2- to 3-carbon fragments like glycolaldehyde, cyanamide or other very simple organic precursors.

Genetic replication, because it includes copying errors - commonly referred to as mutations - allows for evolution - development over time to survive environmental challenges. As they continue to replicate, copying errors - mutations - sometimes introduce advantageous quirks that increase the chance of a given strain multiplying. Because of this, just as living organisms do, simple strains of RNA and its precursors can differentiate and compete within a given environment, ensuring that only the hardiest molecules proliferate and build an enduring lineage.

The problem with artificially-induced RNA chain polymerization in the lab is that it tends to produce random sequences, but if one of these sequences begins to increase its catalytic rate, that is enough to "jump-start" the process of chemical evolution - among the random nucleotide collections, those which replicate the fastest will grow to dominate the chemical "population" - the point at which evolution begins.

Once RNA had emerged, it evolved further into DNA, likely through a process which can be readily seen in the natural world today: retroviruses like HIV synthesize DNA from RNA through a process called reverse transcription

Comparatively more stable, DNA confers a tremendous survival advantage over RNA; it's now used by nearly every known living organism on Earth for storage of the genetic blueprint.

Living cells need a means of containing and protecting their constituent parts. Membrane encapsulation sequesters fragile essential biomolecules, protecting them against environmental hazards and maintaining interior stability. This also allows for individuality - each cell can be different from its neighbor.

When agitated in water, simple fatty acids spontaneously form beads called vesicles. These fatty acid vesicles are potentially stable for months, but on the molecular level, the individual fatty acid molecules are dynamic, perpetually joining and leaving the membrane, and flipping between the inner and outer surfaces. This activity is thought to be the reason simpler fatty acid vesicles are permeable to some organic molecules. This permeability is amplified when heat is applied, and declines as the solution cools.

Tests run upon sample organic molecules from one of the world's most famous meteorites - the Murchison meteorite - demonstrate that fatty acid vesicles will also grow by absorbing free-floating fatty acids - in a sense "eating":

Once organic molecules within a vesicle have become highly concentrated, it creates osmotic pressure - the drive to equalize chemistry both within and without an enclosed membrane, which draws in water - forcing the membrane to expand; the greater the osmotic pressure of the membrane, the more it is driven to syphon off fatty acids from other vesicles, in effect "eating" them.

Thus, an abundance of organic molecules such as RNA trapped in fatty acid vesicles will compel the "feeding" upon other fatty acid vesicles, to increase the membrane surface area, and thereby reduce tension upon it. The force driving the process is this simple osmotic pressure - the need for a cell to equalize the chemistry inside and outside itself.

Fatty acid vesicles can also be shaken into smaller "daughter" vesicles by mechanical force - e.g. waves - without losing the contents. Thus daughter vesicles can "inherit" polymers from the parent. Any monomers which have polymerized inside will have become too large to escape and will be trapped within.

When exposed to high temperatures, such as those near hydrothermic vents, the permeability of vesicle membranes increases, easily absorbing more of the massive flow of organic monomers being formed at such sites. However, these high temperatures tend to break nucleotide bonds. After the membranes cool, however, polymerization can once again occur, and the cycle can be repeated.

Adding a simple alcohol to fatty acids produces lipids, which are more stable. Bonded to phosphates, these produce phospholipids, special polar versions of lipids, with glycerol heads and fatty acid chain tails. The molecule's glycerol head is hydrophilic - attracted to water - while its fatty acid tail is hydrophobic - water repellant. Because of this structure, phospholipids will self-assemble into stable, bilayer vesicles in water.

This is due to water's polarity. In H2O, the oxygen molecule at one end is slightly more negative, because the electrons "prefer" to cluster up near the larger number of protons, leaving the twin hydrogen molecules at the opposite end comparatively more positive.

But fatty acid molecules are non-polar; the number of positive protons and negative electrons are balanced, so they don't carry an attractive or repulsive charge. This prevents them from interacting with water and makes them effective for watertight barriers.

When agitated in water, phospholipids also form beads, potentially trapping any organic matter floating in them - but nucleotides cannot enter or exit phospholipid membranes without special transporter proteins. This means that capturing organic molecules already in water is a trickier matter.

Experiments show that cycles of drying and wetting accomplish the feat: organic molecules are sandwiched between alternating lipid bilayers as they dry. When rehydrated, many of these organic molecules will be captured within the vesicles.

Modern membranes employ phospholipids in double layers, but ancient Earth cells may have used other amphiphilic - both hydrophilic (water-loving/polar) and lipophilic (fat-loving/nonpolar) - chain molecules to form membranes.

Natural selection among these early membrane-protected cells eventually produced the most stable membranes, which today, has come to mean phospholipids embedded with protein receptors, transporters and channels.

Once metabolically-active organic polymers capable of rudimentary replication were sequestered and concentrated within protective membranes, the game was on.

The latest theories say the earliest "pre-life structures" were basically just membrane-bound sacs of water with a few complex chemicals extracting energy from the environment. These floating organic bags randomly collected organic molecules, some of which could assemble into primitive nucleotides to store and perpetuate blueprints for replication.

These organic sacs were protobionts, objects which exhibited some - but not all - of the properties of life, including:
Anatomy - an organized structure
Homeostatic Regulation - the ability to maintain a consistent internal environment
Metabolism - coordinated chemical reactions using energy for repair, mobility, growth and reproduction
Reactivity to environmental stimuli
Adaptability to environmental changes
Growth and development

Danish biochemist Martin Hanczyc specializes in creating and studying protobionts - synthetic chemical systems which skirt the line between living and nonliving matter. Little more than chemically-modified droplets of oil, Dr. Hanczyc's "protocells" engage in many lifelike activities. They move about the environment harvesting "food" - chemical energy for growth and mobililty; they react to environmental changes, showing aversion and attraction; they grow; and they even, to an extent, reproduce and "evolve" into hybrids.

His system is simple, using just five chemicals which spontaneously form bodies that independently locate and interact with resources in their environment.

It's believed that Earth's first protocells - membrane-encapsulated nucleic acids - were well-equipped to outsurvive and outreproduce their less sophisticated chemical brethren. As self-organized, membrane-enclosed collections of self-replicating and protein-synthesizing organic chemicals, these working protocells were the final stepping stone en route to the birth of actual life.

They may have resembled the advanced protobionts made by Dr. Tadashi Sugawara and colleagues at the University of Tokyo - vesicles which grow and self-replicate using DNA. Although not truly alive, these structures exhibit the primary behaviors attributed to life, able to grow and split into new versions of themselves. This is the "bottom up" approach toward finding Earth's earliest life forms.

Meanwhile, at the Institute for Genomic Research's Dr. Craig Venter is trying the "top down" approach - simplifying life to its bare minimum. To do this, he has been gradually eliminating the genes in prokaryotic cells, in an attempt to determine the minimal requirements for life to exist. Dr. Venter is also credited with creating the first truly artificial life on Earth:

We already know creatures on the edge of the life-nonlife divide: viruses - which seem completely lifeless until they attach to a host. Upon entering a host, they then take over its cellular machinery to pump out billions of duplicates of themselves.

Life seems to require surprisingly few genes - Dr. Manfred Eigen's gene-deletion experiments show microbes can potentially survive on as few as 48. But that number is deceptively small, as each gene consists of - on average - 27,000 nucleotides, and some contain as many as two million.

All life needed to be jumpstarted was a single such protobiont which was inefficient at replication, so its copying errors would create a diverse population of descendants. In this way, about three and a half billion years ago, natural selection shaped progessively more sophisticated protobionts, until the first truly living
cells emerged. These were prokaryotes, creatures which lack a DNA-enveloping nucleus, like most modern single-celled organisms.

By analyzing and comparing RNA sequences, we know that at some point in history a single-celled creature we call LUCA - the Last Universal Common Ancestor - produced two different daughter cells. By exploiting different means of energy production, one daughter's lineage would evolve into bacteria, the other into archaea and eukaryotes, a diverse family of organisms which eventually included humans.

Image: The Last Universal Common Ancestor (LUCA), which gave rise to three domains of life Archaea, bacteria, and eukaryotes, all of which share similarities in metabolic and genetic systems. These similarities were derived from LUCA.

Archaea are single-celled organisms cosmetically similar to bacteria, while eukaryotes are cells with internal organelles that can form colonies and multicellular life.

Comparing gene and protein sequences between the three domains of life reveals the ancestral relationships, showing archaea and eukaryotes to be more closely related than either are to bacteria.

Dr. Lynn Margulis of the University of Massachusetts says that the first eukaryotic cells were a product of symbiosis - a mutually beneficial physical partnership between several different archaea. This symbiosis likely formed during horizontal gene transfer, as one cell engulfed another in an attempt to consume it.

Whatever the mechanism behind it may have been, one lineage of archaea initially evolved a membrane to protect its DNA, leading to the Eukaryote (good kernel) lineage. Eukaryotes would then go on to acquire mitochondria and/or chloroplasts - ATP energy-producing structures that carry separate, additional DNA.

Amazingly, this separate DNA very closely matches that of a strain of parasitic bacteria which causes the disease known as rickets. This means that hundreds of millions of years ago, eukaryote cells were invaded by parasitic bacteria, which later evolved to output ATP rather than consuming it, thus establishing a mutually beneficial and permanent partnership. In this way, several independent organisms may have contributed to creating the Last Universal Common Ancestor of all modern life.

“These are the things, like Saturn V rockets, and Sputnik, and DNA, and literature and science –
these are the things that hydrogen atoms do when given 13.7 billion years.” – Dr. Brian Cox, lecture, “CERN’s supercollider”, April 2008, TED Talks

video lectures: Jack Szostak (Harvard/HHMI) Part 1: The Origin of Cellular Life on Earth; Jack Szostak (Harvard/HHMI) Part 2: Protocell Membranes; Jack Szostak (Harvard/HHMI) Part 3: Non-enzymatic Copying of Nucleic Acid Templates;  January 11, 2012, iBiology, US National Science Foundation/National Institutes of General Medical Sciences;

The History of Life on Earth, Biology 160 - Evolution and Biodiversity, Spring 2014, Dr. Dana Krempels, University of Miami;

The Origin of Life, May 3, 2013, Dr. Henry Jakubowski, Biochemistry 331, College of St. Benedict/St. John's University;

NOVA scienceNOW: Where did we come from?, Neil deGrasse Tyson, Mar 23, 2012, Public Broadcasting Service (PBS);

Designing the Molecular World: Chemistry at the Frontier, Philip Bal, 1996 Princeton University Press;

Can Science Explain the Origin of Life?, animated lecture Stated Clearly, 2014, Center for Chemical Evolution, Emory University, Georgia Tech, NASA, National Science Foundation;

The line between life and not-life, lecture, Spring 2011, Dr. Martin Hanczyc, TEDSalon London;

Extraterrestrial nucleobases in the Murchison meteorite, Zita Martins, Oliver Botta, Marilyn L. Fogel, et al, March 20, 2008, Earth and Planetary Science Letters;

Prebiotic Synthesis of Pyrimidine Nucleosides, James P. Collins, November 28, 2005, Georgia Institute of Technology;

Prebiotic Chemistry and the Origin of the RNA World
, Leslie E. Orgel, Critical Reviews in Biochemistry and Molecular Biology, 2004, Taylor & Francis Inc.;

Reconstructed Ancient Ocean Reveals Secrets About the Origin of Life, news release, April 25, 2014, Barry Whyte, European Molecular Biology Organization;

Ancient Oceans' Metals Mimicked Metabolism, James Urquhart, May 1, 2014, Chemistry World;

Power Behind Primordial Soup Discovered, news release, Richard Mellor, April 4, 2013, Richard Mellor, University of Leeds;

Ultraviolet Synthesis of Adenosine Triphosate Under Possible Primitive Earth Conditions,  Ponnamperuma, C., Sagan, C., & Mariner, R., Journal: SAO Special Report #128 (1963)

The RNA World and the Origins of Life,  Molecular Biology of the Cell,  Bruce Alberts, Alexander Johnson, Julian Lewis, etc.;

Life's Origins, Biological Sciences 151, History of Life, Spring 2014, Diana Leigh Lipscomb, Department of Biological Sciences, George Washington University

General Biology 106: Origins of Life,  J. Stein Carter, 1997, Clermont College, University of Cincinnati

Chemist Shows How RNA Can Be the Starting Point for Life, Nicholas Wade, May 13, 2009, New York Times

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