The Origin of Life

[Swammerdami]

The mystery of life's origin was one of the most fundamental and most interesting puzzles in all of science. I use the past tense "was" because Nick Lane argues convincingly in books like The Vital Question that the solution is now in clear view.

I propose this thread to summarize Lane's theory. I hope others will augment or criticize my remarks. (An 18-page 5-author 2016 research paper can be downloaded here. Of course Lane does have detractors, e.g. https://pubmed.ncbi.nlm.nih.gov/27534947/ .)

Key prerequisites for the earliest life are

• Raw materials and organic molecules
• Containment
• Free energy (disequilibrium)
• Self-reproduction

Raw materials are the simplest need to satisfy! Water and dissolved gases -- carbon dioxide, nitrogen, hydrogen -- are sufficient to build organic molecules as long as free energy is available. Water contains dissolved elements like iron and magnesium which are also useful for life. Google 'Origin of Life' and you'll find many hits that focus on the production of simple organic molecules (lipids and especially amino acids and nucleotides) from the simple precursors. By now this discussion is pointless: Forming simple organic molecules is rather easy, and the least of the problems.

Containment is a much more difficult problem. Today's cells have a double layer of phospholipids which provides excellent containment, but these are built by the processes of complex life. Don't expect life to provide much help until its four prerequisites (above) are satisfied. And some types of containment would be an obstacle to early life, which needs access to raw materials and free energy.

A strong source of negative entropy (disequilibrium, or "free energy") is essential to power the assembly of complex organic molecules. Today's life uses photosynthesis, cellular respiration, fermentation or methanogenesis to supply energy but, again, the earliest life couldn't use mechanisms that didn't exist until life was complex. Energy sources like lightning are useless: inadequate or too sporadic. Raw energy like heat or acidity is useless except at a boundary. Where alkaline or hot water meets acidic or cold water: that's where there is entropy production some of which can be diverted to complex processes.

Interestingly, the energy sources for today's life that I just mentioned all use the same basic structure:  Chemiosmosis. Protons (or positively-charged ions like Na⁺ or H₃O⁺) are directed from outside the cell to the inside through an enzyme like ATP-synthase. Photosynthesis and cellular respiration are, in many ways, opposite, yet they use very similar chemistry, many of the same enzymes, and the key step in energy capture is the proton pump just described. The main difference is the energy source which pushed those protons to the outer cell surface in the first place.

Although the very earliest life probably didn't even use ATP — the "energy currency" may have been the much simpler acetyl phosphate — a quote from Nick Lane's book is interesting: "... ATP synthase is indeed a rotary motor, in which the flow of protons turns a crankshaft ... For every ten protons that pass through the ATP synthase, the rotating head [of that protein] makes one complete turn, and three newly minted ATP molecules are released into the matrix."

Finally, self-reproduction is the big prerequisite before life can hope to develop complex structures like cell membranes or ribosomes. But any mechanism for self-reproduction is dependent on the first three prerequisites.

~~~~~~~~~~~~~~~~~~

Underwater thermal vents associated with volcanoes were discovered in 1979 and were proposed as a possible venue for the earliest life. But these vents were too hot, too acidic, and too short-lived. Tiny pores in the towering rock vents ("black smokers") produced as dissolved minerals gushing from the earth's mantle precipitated, might provide containment. But by the time the vent's water was cool enough for organic materials to persist, the water had distanced itself from the vents and was lost in the rush of ocean water.

Theorists began to imagine a different sort of hydrothermal vent. Alkaline where the black smokers were acidic, long-lived where the black smokers were quickly replaced, and somewhat hot where the black smokers were much too hot. (Both types have temperatures far in excess of 100°C but water is kept liquid because of the tremendous pressure.) While black smokers are powered by volcanic activity, the alkaline hydrothermal vents result from the oxidation of olivine ( {Mg²⁺,Fe²⁺}₂SiO₄ ) in the Earth's mantle. (These vents are also the indirect result of volcanic activity, since the olivine won't oxidize until tampered with.)

Such alkaline vents would solve the problems that prevented "black smokers" from being a venue for life's origin. Their temperature is low enough for organic molecules to persist with stability. And the magnesium of olivine dissolved in water (Mg(OH)₂) provides alkalinity. The pores and micropores in the iron pyrite vents would provide the needed containment. (Which size of micropore is the Goldilocks size? It doesn't matter! All sizes are available and life would automatically select the Goldilocks one.) The boundary between the alkaline micropore and the acidic ocean is a disequilibrium which provides the needed free energy. Indeed the H⁺ and other positive charges rushing into the alkaline proto-cell would function exactly as the Chemiosmosis mentioned above. The energy-harvesting of all existing life mimics that free energy available in those micropores. And the FeS of the pores' rocky surface is a good catalyst for some organic syntheses: Indeed many proteins (ferredoxins) use the very same FeS combination at their catalytic core.

In 2000 these hypothesized alkaline hydrothermal vents were discovered.  Lost City Hydrothermal Field.

 

[Swammerdami]

When I was a kid we learned of a Three-Kingdom model of Life: Animals, Plants and a 3rd Kingdom of Unicellular life with Protista and Bacteria lumped together. I was already an adult when a Five-Kingdom model was proposed: Eukaryotic Protista separated from Prokaryotes, and Fungi split off from Plants.

Today that Five-Kingdom model is laughed at. Bacteria is split into two Domains: Bacteria and Archaea; and the Eukaryotic Kingdoms form a third Domain. The Eukaryote Domain is subdivided into six or so Kingdoms for a total of eight (or so) Kingdoms in Life's Phylogeny.

• Bacteria
• Archaea
  
  
• Archaeplastida - plants, green algae, red algae, etc.
• Opisthokonta - animals, fungi
• Rhizaria - foraminifera, radiolarians, etc.
• Amoebozoa - amoeba, slime molds, etc.
• Chromalveolata - stramenopiles (brown algae, diatoms), ciliates, malaria parasites, etc.
• Excavata - euglena, etc.

Note that now, despite the larger total number of Kingdoms, animals and fungi are lumped into a single Kingdom.

The first split in the Tree of Life was between Bacteria and Archaea, and that split occurred (according to Nick Lane) when life was still largely confined to the micropores of hydrothermal vents. An ancient proto-cell that had two children (a proto-bacterium and a proto-archaeote) is called LUCA — the Last Universal Common Ancestor. LUCA's children had DNA and mechanisms developed to exchange DNA (even between bacteria and archaeotes) so evolution was rapid. These primitive creatures had lots of DNA genes to choose from but kept only the best! Organisms with wasted DNA reproduced more slowly than organisms that kept a trim set of useful genes.

Then, billions of years after LUCA, a singular event occurred. An archaeote somehow engulfed a bacterium (proto-mitochondrium) and evolved rapidly. With thousands of mitochondrial membranes to power energy production, a cell nucleus could develop with a much larger genome ... and the Eukaryotes were born!

But this thread is about the "Origin of Life," so we will focus on life's development up until LUCA. We know LUCA was primitive in some ways, because bacteria and archaeota have different types of cell membranes and cell walls, different mechanisms for DNA replication, and different details in the fundamental citric acid cycle.

 

[Swammerdami]

With amino acids and nucleotides clogging up the micropores, it was easy for peptide chains or nucleic acid chains to form. Normally such chains would float off into the ocean and disintegrate, but trapped in the clog of organic material they would grow. The FeS on the surface of the micropore would catalyze the production of these chains, which in turn might catalyze the production of more organic precursors, e.g. via the citric acid cycle. But life couldn't advance without self-reproduction.

Polypeptides are produced almost automatically when amino acids mate, but nucleic acids require a backbone. Primitive nucleic acids have been synthesized using an amino acid chain for the backbone, but RNA's backbone contains both ribose and phosphate. It is likely that the earliest proto-life used a simpler nucleic acid ( Peptide_nucleic_acid#PNA_world_hypothesis) and that only from that could the ribose-phosphate backbone be built, but this is speculative, so our story begins with RNA. Recently researchers have been delighted to discover RNA sequences that reproduce themselves! One RNA chain with length about 200 bases can copy other RNA chains several dozen bases in length IIUC. A pair of chains have been discovered with RNA_A catalyzing the production of RNA_B and vice versa; all without protein assistance. OTOH, recently a poly-peptide chain has been discovered which seems to grow itself without RNA assistance. The details of the self-replication which led to Life are unknown, but it was possible ... and therefore with zillions of nucleic acid and peptide chains floundering about and bumping into each other ... inevitable.

Traditionally, catalysts formed from peptide chains are called enzymes; catalysts formed from RNA are called ribozymes. It wasn't well-understood when I was a kid, but today it is known that r-RNA, and not any protein enzyme, provides the key site in the ribosome needed for protein synthesis. t-RNA's are also complex ribozymes needed for the ribosome.. An  RNA World is hypothesized where early life didn't even need proteins. But I think protein synthesis began early, with the  Genetic Code an essential part of that. Nick Lane shows how the details of the genetic code could develop gradually, from simple natural reactions. (Similarly, the enzymes that drive the citric acid cycle were just speeding up processes that occurred naturally. And so on.) With the Genetic Code in place, protein enzymes arose to assist the ribosomes. This was the  RNP world, possibly preceded by afore-mentioned RNA World.

One bacterium has thousands of ribosomes, a eukaryote cell has millions. The large majority of the genes that LUCA possessed were the genes needed for ribosomes, the genetic code, and related functions (steering raw materials to the ribosome and completed proteins away from it).

Another essential feature of the earliest cells was genome replication. Once DNA was "invented," there are four types of gene replication to consider: DNA -> RNA, DNA -> DNA, RNA -> RNA, and RNA -> DNA. Only the first two of these four are present in today's life (although the enzymes needed for the other two cases may have mutated to serve other functions), but RNA -> RNA replication is used by coronaviruses (etc.) and RNA -> DNA "reverse transcription" is performed by retroviruses like HIV. Since both these mechanisms were needed at some point by the earliest life, it is possible that viruses descend from such long-ago very primitive proto-cells.

The earliest proto-cells lacked DNA and had only mechanisms for RNA -> RNA transcription. But DNA is very similar to RNA and at some point that mechanism mutated to develop RNA -> DNA and DNA -> RNA transcription. DNA -> RNA -> Protein is now the universal pattern for all life, with RNA -> RNA and RNA -> DNA transcription no longer needed. It may seem needlessly complex, but DNA is stabler and more suited to long-term genome storage than RNA, while RNA is flexible and more suited to protein synthesis.

The genes and associated enzymes to transcribe DNA into RNA were present in LUCA (though Bacteria and Archaea have separate mechanisms for DNA -> DNA replication). There are also a few universal genes associated with metabolic processes like the citric acid (Krebs) cycle. In the next post I will complete my summary of LUCA by mentioning two other universal enzymes: ATP synthase and the Sodium-Proton Anti-Porter (SPAP).

 

[Swammerdami]

Earliest proto-cells probably used a simple molecule like Adenine Phosphate as "energy currency" but LUCA used Adenosine Triphosphate, and essentially all her descendants have ATP Synthase (mentioned earlier in the thread) which harvests energy from a proton or other positive ion and uses it to build ATP, the energy currency of all cells. While the membranes that cells eventually developed deny admittance even to H⁺ (protons), the channel of ATP Synthase embedded in the membrane can admit not only protons but larger ions like Na⁺ or H₃O⁺.

SPAP, the Sodium-Proton Anti-Porter, exchanges Na⁺ and H⁺ ions. Like many enzymes it can be used in two opposite ways: it can be configured to pump sodium ions into the cell (with H⁺ going out) or to pump sodium ions out of the cell (with H⁺ coming in). Apparently its earliest use was to pump Na⁺ out of the proto-cell. By replacing the protons on the proto-cell's external surface with larger sodium ions, it becomes more likely that the charges will be directed through the ATP Synthase, rather than uselessly crossing back in via a weak or non-existent membrane. According to Nick Lane, this mechanism was a prerequisite for the energy-yielding proton pumps which replaced the free chemiosmosis available in alkaline micropores, and motivated the cell membranes resistant to proton back-flow, which greatly amplified the efficiency of the proton pump for energy production. Indeed he might argue that membranes were counter-productive before the SPAP enzyme evolved.

After the "invention" of SPAP and ATP Synthase, bacteria and their archaeota cousins were more efficient and were free to develop cell membranes, leave their cozy micropores, and fend for themselves, first via methanogenesis and later with other energy sources like photosynthesis.

This concludes my summary of Lane's Origin of Life theory. I hope others will join in and augment, criticize or amend these remarks.

 

[Swammerdami]

I am disappointed there's been no comment in this thread. Surely my exposition wasn't error-free, let alone an optimal summary of these ideas. Anyway, here are some further comments and questions.

My summary should have mentioned that initial evolution may have been very slow, due to the difficulty of successful reproduction before effective cell fission, membranes and other efficiencies. Lateral Gene Transfer (LGT) was important to evolutionary speed. Does anyone know how frequent that mechanism is today? (That is, if you traced a typical bacterium back through its mother, grandmother, etc. for a million generations, how many of those individual bacteria received new DNA via LGT?) Recent studies have shown that eukaryotes occasionally receive genes from other eukaryotes via LGT. (Rice is in the same family as bamboo and corn; rice's uniqueness is thought partly due to fungal genes which presumably arrived via LGT.)

There was surely a long delay between the earliest proto-life and LUCA, and then further long delays until LCA-Bacteria and LCA-Archaea. Never mind the origin and early development of Eukaryotes — that needs its own thread.

The more I read about biochemistry and the origin of life, the more life's chemistry seems fortuitous and the harder it is to imagine life based on anything other than the carbon- and water-based complex molecules we see on Earth. Sure, trivial changes are possible: different amines or nucleotides; and other molecules could play the role of ribose in RNA and DNA. But the electrical charges of the polyanionic phosphate (PO₃^-) backbone of RNA and DNA provide essential properties. Is there another polyanionic or polycationic polymer that could be substituted?

Recently researchers under CalTech's Frances Arnold have designed bacterial genes that produce organo-silicon molecules that humans can't otherwise produce! But that's not the same as silicon-based life. Polysiloxane (probably with carbon-based side-chains) might be a possible backbone for life in some hot acidic conditions, but will this uncharged chain have the desired properties of RNA's phosphate backbone? Perhaps a backbone alternating phosphate with siloxane is the "recipe" for silicon-based life.

 

[rousseau]

I am disappointed there's been no comment in this thread. Surely my exposition wasn't error-free, let alone an optimal summary of these ideas. Anyway, here are some further comments and questions.

For my part I've always just assumed - more generally - that it was a chemical process where molecules began reproducing themselves, and tacking on 'features' that promoted more efficient reproduction. Not unlike what we see today, but with very primitive chemical structures. I found Dawkins' explanation of this in The Selfish Gene very good.

Beyond that I've never really thought to dive into the minutiae, because personally I'm not a huge fan of chemistry or bio-chemistry. Unfortunately, I don't know that you'll find this level of specialist knowledge amount the members here.

 

[Swammerdami]

Yes; and perhaps I delved too deep into minutiae in this summary.

The big headline is that Lane et al have identified the venue for life's origin -- the alkaline hydrothermal vents which weren't even discovered until 2000.

Synthesis of organic molecules and even polymers is easy. It's Containment and Free Energy that are tough for the very earliest proto-life. The alkaline hydrothermal vents solve both problems in a fell swoop.

 

[rousseau]

Yes; and perhaps I delved too deep into minutiae in this summary.

The big headline is that Lane et al have identified the venue for life's origin -- the alkaline hydrothermal vents which weren't even discovered until 2000.

Synthesis of organic molecules and even polymers is easy. It's Containment and Free Energy that are tough for the very earliest proto-life. The alkaline hydrothermal vents solve both problems in a fell swoop.

So what's the degree of confidence that this finding is correct?

I'll likely go through your posts but haven't had time to give them proper focus yet.

 

[Swammerdami]

All energy production in living cells relies on proton transfer ("chemiosmosis"), which is equivalent to the free energy available when a cell's exterior is acidic relative to its interior. (In eukaryotes the pH gradient is across internal membranes, not the cell boundary.) Hot alkaline water spurting up from the depths into the micropores of underwater vents fits this role perfectly; the hypothesis has been developed in several journal articles starting decades ago.

The emphases in my summary in this thread are quite different from those in Lane's book, which in turn are different from the emphasis in the Sojo et al journal article I cited.

The big headline is that Lane et al have identified the venue for life's origin -- the alkaline hydrothermal vents which weren't even discovered until 2000.

Synthesis of organic molecules and even polymers is easy. It's Containment and Free Energy that are tough for the very earliest proto-life. The alkaline hydrothermal vents solve both problems in a fell swoop.

So what's the degree of confidence that this finding is correct?

Are you asking for the consensus views of relevant experts? I don't know ... and am not sure how "relevant expert" would be defined. The mechanics of the vents are relevant, as well as the very simple chemistry of the proton transfers, as is imagining the complicated origin of life and viewing the hypothesized scenario in context. Perhaps a biochemistry PhD is necessary to qualify as "relevant expert" but it certainly is not sufficient.

Given my experience on other controversial topics where broad expertise is needed, I am reluctant to base my own opinion on a simple majority view of self-appointed experts.

One specific fact which I think is a strong clue: The pyrite walls of the alkaline vents have Fe-S sites which can serve as catalysts for important organic reactions. The ferredoxin enzymes present in LUCA contain Fe-S sites (with the same inter-atom distance as in crystalline pyrite IIUC) that mimic the catalysis of the micropore walls. LUCA's repertoire of enzymes built up gradually, augmenting or mimicking the proto-life processes already occurring naturally in the micropore.

In post #1 I mentioned a paper by J. Baz Jackson which disputes this hypothesis. Researchgate is a good place to download journal articles for free.

It is forcefully argued by Lane et al. (2010) that ‘‘chemiosmosis was central to the origin of life’’. These authors conclude it is ‘‘nearly impossible’’ to see how life could have begun in the absence of natural pH gradients,and that ‘‘chemiosmosis was necessary’’. The justification for this uncompromising view seems partly to stem from the RML groups’ own definition of primordial soup. They imply, but do not explore in rigorous detail, that chemical reactions in the primordial soup would have reached thermodynamic equilibrium, and that further steps on the chemical pathways leading to living organisms would have become impossible without energetic input from a natural pH gradient. The idea is at its most extreme (and startling) in Martin and Russell (2003) where, of course by analogy, it is said that ‘‘once autoclaved a bowl of chicken soup at any temperature will never bring forth life’’. The RML perspective is probably not at all justified on thermodynamic grounds since we do not know enough even approximately to define the prebiotic system.

The paper goes on for several pages but I find it utterly non-compelling. Jackson ignores that energy production is a prerequisite for ribosomes and genome replication, not vice versa. He also ignores that in a complex vent, there will be "Goldilocks" micropores with just the right size and just the right inorganic membrane thickness; and life will "choose" such Goldilocks venues for its origin automatically!

 

[lpetrich]

I myself have considered this question: To the Origin of Life - the Early Evolution of Biosynthesis and Energy Metabolism

First, it must be noted that eukaryotes aren't anywhere close to the LUCA, but a hybrid that emerged much later.

The LUCA was a DNA-RNA-protein organism much like present-day ones. In fact, methanogens are very LUCA-like. They and the LUCA share:

• A full-scale DNA-RNA-protein apparatus
• Autotrophic biosynthesis: they make all their biological molecules
• Lithotrophic energy metabolism: they live off of inorganic-chemistry reactions
• Being obligate anaerobes: not using oxygen and being poisoned by present-day levels of oxygen
• Electron-transfer metabolism
• Chemiosmotic metabolism with ATP synthesis
• Many of the enzyme cofactors present in present-day organisms: B vitamins, porphyrins, etc.

The LUCA likely had two carbon-fixation pathways side by side: the reductive tricarboxylic-acid cycle and the Wood-Ljungdahl pathway. These two pathways combine carbon dioxide with virtual hydrogens (electrons + hydrogen ions) to make biological molecules.

It also had nitrogen fixing: N2 + 6 (virtual H) -> 2NH3
The ammonia is then incorporated into biological molecules.

It likely also had denitrification, (nitrogen oxides) -> N2

It likely could reduce sulfates and sulfites to sulfides: H2SO4 + (8 virtual H) -> H2S + 4H2O

 

[lpetrich]

It's rather obvious that such a complicated organism would have trouble directly emerging from a prebiotic environment. So it must have a lot of evolution behind it.

The most successful hypothesis so far of pre-LUCA evolution has been the RNA world. In it, RNA served as both information storage and enzyme, without DNA or proteins, though amino acids and simple proteins may have been present. In fact, the main criticism that I've seen of it is that it's hard to make RNA prebiotically. It seems to me that if that's the main problem with it, then going from the RNA world to the present-day DNA-RNA-protein world must be relatively uncontroversial.

Ribosomes are a relic of the RNA world, since their most important parts are their RNA strands. Their proteins are later additions. The same is true more generally of the RNA-to-protein translation apparatus.

DNA is essentially modified RNA. In fact, its building blocks are made by modifying RNA ones.

Some cofactors are used with bits of RNA. For example, the B vitamin niacin looks like some modified nucleobase, and it substitutes for a nucleobase in where it is used: NAD and NADP. So we can be confident that niacin dates back to the RNA world. Similar reasoning applies for some other cofactors, like riboflavin and pantothenate. Porphyrins also likely date back to the RNA world.

Modified nucleobases are also used in transfer and ribosomal RNA, so we can conclude that the RNA world had modified nucleobases in its RNA.

ATP most likely dates back to the RNA world, since it is a nucleotide with extra phosphates attached to its phosphate.

 

[lpetrich]

Proteins likely originated as cofactors for the RNA world's ribozymes. They were eventually elaborated until they took over enzyme duties.


There is a serious problem with the prebiotic synthesis of RNA: the synthesis of its ribose, a 5-carbon sugar. The big problem is that nucleic acids depend on some characteristic asymmetries in that molecule, meaning that those asymmetries cannot be mirror imaged without becoming nonfunctional. For instance, one can make mirror-image nucleic acids, but they will not fit with ordinary ones.

One can make ribose with the Butlerov formose reaction, starting with formaldehyde. But one makes a lot of different sizes of sugar, and different mirror-image variants of the asymmetries for each size.

If a carbon atom is attached to four separate atoms, then those atoms will approximately be on the corners of a regular tetrahedron. If those atoms are all different or have different stuff attached to them, then the carbon atom will be an "asymmetric carbon atom", and it will have two mirror-image variants.

Proteins-forming amino acids have an asymmetric carbon atom in them with a characteristic asymmetry, except for glycine. Ribose has four asymmetric carbon atoms.


A way out of this conundrum is to suppose that RNA was not the first, that it took over from some earlier replicator. I've seen hypotheses like peptide nucleic acids (peptide = amino-acid chain) and PAH nucleic acids (PAH = polycyclic aromatic hydrocarbon). But that is still very speculative.