To the Origin of Life - the Early Evolution of Biosynthesis and Energy Metabolism

[lpetrich]

I'll be posting on some stuff I'd collected some years ago -- stuff that I'll be wanting to update wherever possible.

Did DNA replication evolve twice independently? [Nucleic Acids Res. 1999] - PubMed - NCBI In Bacteria and Archaea (or Eubacteria and Archaebacteria) separately, with eukaryotes inheriting their DNA-replication system from Archaea.

Modern mRNA proofreading and repair: clues that the last universal common ancestor possessed an RNA genome? [Mol Biol Evol. 2005] - PubMed - NCBI

I've seen the theory that the LUCA (Last Universal Common Ancestor) had a heteroduplex genome, with DNA and RNA strands bound to each other. But the LUCA did have DNA, meaning that DNA had a pre-LUCA origin. DNA building blocks are built from RNA ones, first by chemically reducing the ribose parts to deoxyribose, then by adding a methyl group to uracil, making thymine. DNA without the second step is uracil-DNA.

Also pre-LUCA is the protein-synthesis apparatus. It involves transcription from genomic DNA to messenger RNA, and translation from mRNA to proteins. This translation is done with the help of RNA-protein complexes called ribosomes, and the RNA in them seems to be their most essential part. The translation involves transfer RNA's, snippets of RNA where one end fits the mRNA, and the other end has an amino acid attached. Amino acids are the building blocks of proteins. Transfer RNA's are notable for having nucleobases that were modified after being transcribed from the genome, postttranscriptional modification. Some of these modified nucleobases make their tRNA's capable of matching onto more than one mRNA nucleobase, enabling one tRNA to match onto several different three-nucleotide "codons".

So we see so far RNA, RNA, RNA, and more RNA. RNA can act as an enzyme, and some enzyme cofactors contain bits of RNA: Coenzymes as coribozymes. [Biochimie. 2002] - PubMed - NCBI, Modern metabolism as a palimpsest of the RNA world. [Proc Natl Acad Sci U S A. 1989] - PubMed - NCBI mention B vitamins B1 (thiamine), B2 (riboflavin), B3 (niacin), B5 (pantothenate), B6 (pyridoxal).

The remaining B vitamins are B7 (biotin), B9 (folate), and B12 (cobalamin). Biotin likely emerged after proteins did, not in the RNA world. B12 has a porphyrin ring, and porphyrins likely date back to the RNA world, if not farther.

Niacin's more formal name is nicotinic acid, and it occurs as nicotinamide adenine dinucleotide (NAD), a length-2 RNA snippet. The nicotinamide part looks suspiciously like some modified nucleobase.

Another cofactor is ATP, adenosine triphosphate: (adenine) - (ribose) - (P) - (P) - (P) where the (P) is a phosphate ion. It is often used as an energy intermediate, and that energy resides in its phosphate-phosphate bonds. When used in that fashion, it gets reduced to adenosine diphosphate (2 phospates) or adenosine monophosphate (1 phosphate), and it gets rebuilt by adding phosphates to make ATP again.

More and more and more RNA.

Because of all that RNA, the RNA world has become a very widely accepted hypothesis.

 

[lpetrich]

The RNA world hypothesis: the worst theory of the early evolution of life (except for all the others)a | Biology Direct | Full Text discusses some criticisms of that hypothesis.

Like: RNA is too complex a molecule to have arisen prebiotically

Its building blocks have the structure (phosphate) - (ribose) - (nucleobase) and they join together in a chain with structure
(R) - (N)
(P)
(R) - (N)
(P)
(R) - (N)
(P)

Though one can make some nucleobases prebiotically, it's very hard to do so for ribose. I've seen theories that it was not the first backbone molecule, that it had predecessors like amino acids or polycyclic aromatic hydrocarbons.

He also notes: RNA is inherently unstable. Catalysis is a relatively rare property of long RNA sequences only. The catalytic repertoire of RNA is too limited

Proteins are also limited, even if not as much. That is why some enzymes include cofactors, including metal ions. Some cofactors are plausibly traced back to the RNA world, indicating that RNA enzymes had help, just as protein enzymes do.

Then some stuff on the possible origin of ribosomes as protein enzymes for replicating RNA. I find it very unconvincing, since it is very hard to make a protein replicator. But with nucleic acids, replication is almost trivially easy -- a nucleic-acid strand can be used as a template for making a copy of itself. Watson and Crick themselves noticed that when they worked out the structure of DNA: "It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material."

 

[lpetrich]

The physiology and habitat of the last universal common ancestor | Nature Microbiology

The concept of a last universal common ancestor of all cells (LUCA, or the progenote) is central to the study of early evolution and life's origin, yet information about how and where LUCA lived is lacking. We investigated all clusters and phylogenetic trees for 6.1 million protein coding genes from sequenced prokaryotic genomes in order to reconstruct the microbial ecology of LUCA. Among 286,514 protein clusters, we identified 355 protein families (∼0.1%) that trace to LUCA by phylogenetic criteria. Because these proteins are not universally distributed, they can shed light on LUCA's physiology. Their functions, properties and prosthetic groups depict LUCA as anaerobic, CO2-fixing, H2-dependent with a Wood–Ljungdahl pathway, N2-fixing and thermophilic. LUCA's biochemistry was replete with FeS clusters and radical reaction mechanisms. Its cofactors reveal dependence upon transition metals, flavins, S-adenosyl methionine, coenzyme A, ferredoxin, molybdopterin, corrins and selenium. Its genetic code required nucleoside modifications and S-adenosyl methionine-dependent methylations. The 355 phylogenies identify clostridia and methanogens, whose modern lifestyles resemble that of LUCA, as basal among their respective domains. LUCA inhabited a geochemically active environment rich in H2, CO2 and iron. The data support the theory of an autotrophic origin of life involving the Wood–Ljungdahl pathway in a hydrothermal setting.

There is a lot to unpack here.

• Anaerobic: the LUCA did not use oxygen or release that gas, and that gas was likely poisonous to it.
• CO2-fixing: it got its biological-molecule carbon from CO2.
• H2-dependent: it lived off of hydrogen gas.
• Wood-Ljungdahl pathway: it takes CO2 and H2 and makes acetic acid: CH3COOH -- did the LUCA piss vinegar?
• N2-fixing: it got its biological-molecule nitrogen from N2.
• Thermophilic: it liked high temperatures, like 80 C.
• FeS clusters: iron-sulfur clusters in its enzymes
• Transition metals: vanadium, manganese, iron, cobalt, copper, zinc, molybdenum, ...
• Flavins: riboflavin (vitamin B2) with RNA building blocks and proteins. Involved in electron-transfer metabolism.
• S-adenosyl methionine: the amino acid methionine with a RNA building block. Involved in the transfer of methyl: CH3- groups.
• Coenzyme A: the amino acid cysteine and pantothenic acid (vitamin B5) along with a RNA building block. Involved with acetic acid.
• Ferredoxin: an enzyme with iron-sulfur clusters that is involved in electron-transfer metabolism.
• Molybdopterin: a carrier of molybdenum that is much like folic acid (vitamin B9)
• Corrins: porphyrin-like rings that are in vitamin B12.
• Selenium: a sulfur-like element that sometimes substitutes for sulfur.

It also did modification of RNA nucleobases, such as what is in transfer RNA's.

So all in all, it was a rather complicated organism, and there is evidence that it had a lot of evolution behind it.

 

[lpetrich]

The Emergence and Early Evolution of Biological Carbon-Fixation by authors Madeline C. Weiss, Filipa L. Sousa, Natalia Mrnjavac, Sinje Neukirchen, Mayo Roettger, Shijulal Nelson-Sathi & William F. Martin.

That paper's authors propose that the LUCA had not one, but two carbon-fixation pathways, two ways of capturing CO2: the Wood-Ljungdahl pathway and the citric-acid cycle. That latter one is also called the tricarboxylic acid cycle and the Krebs cycles. The W-L pathway makes methyl groups and acetic acid, while the citric-acid cycle produces starter molecules for several amino acids.

The  Wood–Ljungdahl pathway:

The first part uses a relative of folic acid, tetrahydrofolate:
CO2 + 2H+ + 2e + ATP + H2O -> HCOOH + ADP + Pi (free phosphate ion)

e = electron, and in LUCA-ish organisms and the LUCA itself, it comes from hydrogen gas.

The THF itself starts off as -NH HN- (I won't try to draw the rest of the molecule)
-NH HN-
HCOOH ->, -> H2O
-N-CHO HN-
H+ ->, -> H2O
-N-CH=N(+)-
H+ + 2e ->
-N-CH2-N-
2H+ + 2e ->
-NH CH3-N-

This methyl group: CH3- is then handled by various other enzymes and coenzymes. For biosynthesis, it is attached to other molecules. But in methanogens, it gets a final 2H+ + 2e and becomes methane.

The second part of the W-L pathway:
CO2 + 2H+ + 2e -> CO + H2O
CH3-X + CO + CoA-SH -> CoA-S-(C=O)-CH3 + H-X
Thus making acetyl coenzyme A. The acetyl part may then be used for additional biosynthesis tasks, or else released as acetic acid by adding water.

 

[lpetrich]

Here is the  Citric acid cycle. Biochemists often like to use -ate instead of -ic acid in the names of acids. Thus, acetate instead of acetic acid.

Citrate: COOH-CH2-(HO)C(COOH)-CH2-COOH
CoA-SH (coenzyme A) ->, -> H2O + CH3-CO-S-CoA (acetyl coenzyme A)
Oxaloacetate: COOH-CH2-CO-COOH
2H+ + 2e ->
Malate: COOH-CH2-HCOH-COOH
-> H2O
Fumarate: COOH-CH=CH-COOH
2H+ + 2e ->
Succinate: COOH-CH2-CH2-COOH
CoA-SH ->, -> H2O
Succinyl CoA: COOH-CH2-CH2-CO-S-CoA
CO2 + 2H+ + 2e ->, -> H2O + CoA-SH
Alpha-ketoglutarate: COOH-CH2-CH2-CO-COOH
2H+ + 2e + CO2 ->
Isocitrate: COOH-CH2-(H)C(COOH)-HCOH-COOH
(rearranged)
Citrate: COOH-CH2-(HO)C(COOH)-CH2-COOH

As one can tell, both the W-L pathway and the citric acid cycle consume electrons and CO2 molecules and make acetic acid.

The citric-acid cycle supplies raw materials for making several protein-forming amino acids. Here are the ones with the simplest pathways for making them (somewhat simplified):

Oxaloacetate: COOH-CH2-CO-COOH
-NH2 ->
Aspartate: COOH-CH2-CH(-NH2)-COOH
-NH2 ->
Asparagine: NH2-CO-CH2-CH(-NH2)-COOH

Alpha-ketoglutarate: COOH-CH2-CH2-CO-COOH
-NH2 ->
Glutamate: COOH-CH2-CH2-CH(-NH2)-COOH
-NH2 ->
Glutamine: NH2-CO-CH2-CH2-CH(-NH2)-COOH

 

[bilby]

Here is the  Citric acid cycle. Biochemists often like to use -ate instead of -ic acid in the names of acids. Thus, acetate instead of acetic acid.

That's a reasonable position to take in the context of biochemistry, which mostly occurs in highly impure aqueous solutions where multiple anions (and cations) are present. When the cation is the important group, as is invariably the case when discussing acids (H⁺ being the most common and least interesting of the possible anions in an acid solution, by definition), and several anions are present in solution (most biological contexts have plenty of K⁺, Na⁺ and often Mg²⁺ and Ca²⁺ present as well as the ubiquitous H⁺), there is no good reason to specify the anion, and the use of the '-ic acid' suffix might be taken as implying that it is specifically and exclusively H⁺.

Biochemists and organic chemists have a habit of ignoring H⁺ ions, and even covalently bonded H, as it is just assumed to be there by default if no other group or anion is specified.

 

[lpetrich]

These amino groups come from nitrogen fixation, and it uses an enzyme called  Nitrogenase. It essentially does
N2 + 6H+ + 6e -> 2NH3

Nitrogen fixation does not work well in oxygen, and some organisms have ways of protecting their N2 fixation from O2. Some cyanobacteria live in strands, with their cells being like beads on a string, and some of them may become "heterocysts", cells specialized for nitrogen fixation. To avoid poisoning their N2 fixation with O2, they depend on their neighbors for photosynthesis.

There are two possible pathways for reducing nitrogen to ammonia: distal and alternating. M is the metal ion that the nitrogen is attached to.
The M is some metal ion. A triple bond I will denote with a #: N#N

Distal:
M-N#N
M-N=NH
M=N-NH2
M=N-NH3+
M#N + -NH3+
M=NH
M-NH2
M-NH3+
M + -NH3+

Alternating:
M-N#N
M-N=NH
M-NH=NH
M-NH-NH2
M-NH2-NH2
M-NH2-NH3+
M-NH2 + -NH3+

 

[lpetrich]

Evolution of the first metabolic cycles by Günter Wächtershäuser (1990): He proposed that the reductive citric-acid cycle is prebiotic. I've found Uncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid Cycle | Scientific Reports "Reverse" meaning in the reductive direction. "Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended." -- meaning that it is likely one of several similar sorts of cycles that could have emerged prebiotically.


Porphyrins are rings of rings that are found in various places. With what metal ions are in their centers:

• Cobalt ion: vitamin B12
• Iron ion: heme -- in cytochromes, hemoglobin, ...
• Magnesium ion: chlorophyll

I looked at the structure of a version of vitamin B12,  Cyanocobalamin, and I found a RNA building block in it. So it likely goes back to the RNA world. I've also found:

Possible origin for porphin derivatives in prebiotic chemistry--a computational study. [Orig Life Evol Biosph. 2005] - PubMed - NCBI
Prebiotic Porphyrin Genesis: Porphyrins from Electric Discharge in Methane, Ammonia, and Water Vapor -- PNAS
So porphyrins may be prebiotic.

Their biosynthesis occurs by two pathways: C5 and Shemin. The Shemin one is only in alpha-proteobacteria and nonphotosynthetic eukaryotes; the C5 one is in everything else. So the Shemin one was likely invented by some early alpha-proteobacterium and incorporated into eukaryotes with the ancestor of the mitochondria. The C5 one was returned to eukaryotedom by the cyanobacterium that became the ancestor of the chloroplasts.


Terpenes, or terpenoids or isoprenoids more generally, are polymers of isoprene:
CH2 = C (-CH3) = CH2

They are present in a variety of places across all three domains, and they may date back to the RNA world: cell-membrane lipids in Archaea, chlorophyll, carotenoids, and quinones in Bacteria, and the raw material for steroids in Eukarya. They get their name from turpentine, something produced by conifer trees.

Isoprenoid biosynthesis: The evolution of two ancient and distinct pathways across genomes | PNAS Those are pathways for making isoprene. Archaea mostly use the mevalonate (MVA) pathway and Bacteria the deoxyxylulose 5-phosphate (DXP) pathway.

Eukaryotes are a mixture. Animals and fungi use the MVA pathway, while plants and algae have both. In "higher" plants, MVA is used for steroids, with DXP for all other terpenoids. The DXP rather evidently came with the chloroplasts, though not with the mitochondria.

 

[DrZoidberg]

It could have evolved independently lots of times. Nature has a way of destroying evidence

 

[fromderinside]

Circling back is so fun to do. Wonder if it has anything to do with cyclicity of such as weather.

 

[Worldtraveller]

Here's a nice link to add to this topic:

https://www.sciencemag.org/news/201...medium=website&utm_content=link&ICID=ref_fark

Now, a team of researchers has shown for the first time that a set of simple starting materials, which were likely present on early Earth, can produce all four of RNA's chemical building blocks.

Carell's story starts with only six molecular building blocks--oxygen, nitrogen, methane, ammonia, water, and hydrogen cyanide, all of which would have been present on early Earth. Other research groups had shown that these molecules could react to form somewhat more complex compounds than the ones Carell used.

To make the pyrimidines, Carell started with compounds called cyanoacetylene and hydroxylamine, which react to form compounds called amino-isoxazoles. These, in turn, react with another simple molecule, urea, to form compounds that then react with a sugar called ribose to make one last set of intermediate compounds.

Finally, in the presence of sulfur-containing compounds called thiols and trace amounts of iron or nickel salts, these intermediates transform into the pyrimidines cytosine and uracil. As a bonus, this last reaction is triggered when the metals in the salts harbor extra positive charges, which is precisely what occurs in the final step in a similar molecular cascade that produces the purines, adenine and guanine. Even better, the step that leads to all four nucleotides works in one pot, Carell says, offering for the first time a plausible explanation of how all of RNA's building blocks could have arisen side by side.

Interesting times.

 

[lpetrich]

Titled link: Chemists find a recipe that may have jump-started life on Earth | Science | AAAS

That gives us all four of the standard RNA nucleobases with one set of reaction conditions. Previous efforts had made the purines (adenine, guanine) in one set of conditions and the pyrimidines (uracil, cytosine) in another set. Purines have two carbon-nitrogen rings, pyrimidines only one.

A RNA nucleotide has a structure: (phosphate) - (ribose) - (base)
A nucleoside, with t -> s in its name, has only (ribose) - (base)

Ribose is a five-carbon sugar, and it is the missing piece of the puzzle. Prebiotic ribose synthesis: a critical analysis. - PubMed - NCBI by R. Shapiro (1988), The Origins of the RNA World by Michael P Robertson and Gerald F Joyce (2012). It's difficult to make ribose prebiotically. The most plausible way of doing so is with the Butlerov formose reaction, and it requires a lot of fairly pure formaldehyde. Even then, it does not produce much ribose -- it's mixed in with a lot of other sugars with other lengths and asymmetries.

I favor the solution in the second paper, that ribose was not the first backbone molecule, that it replaced something else that came before it. But what it was is not very certain.

 

[lpetrich]

 Electron transport chain -- it is an important part of energy metabolism, and it is also involved in biosynthesis. It involves sending electrons along a series of enzyme complexes and cofactors, in a series of redox (reduction-oxidation) reactions.

I note that biochemists like to call hydrogen ions protons, even though about 1 in 6400 of them are deuterons, H-2 nuclei.

I will discuss the mitochondrial version first, since it been very well-researched, and since it has some typical features. The transfer-chain enzyme complexes live in the mitochondrion's inner membrane

It starts with charging up NAD (niacin, B3):
(HC-OH) + NAD+ -> (C=O) + NADH + H+

Complex I, with the enzyme NADH dehydrogenase, transfers electrons from NADH to a flavin (riboflavin, B2), making flavin-H2. It then transfers those electrons to a quinone, making plain flavin again. In the process, it takes protons from the inner-membrane interior and releases them in that membrane's exterior.
In the process, the quinone becomes quinone-2H, taking protons from the interior.

Another reaction is
(CH2 - CH2) + flavin -> (CH = CH) + flavin-2H
using a different flavin in Complex II. It does not push protons across the membrane, however.

The quinone then goes to Complex III, the cytochrome-bc1 complex. It transfers electrons from quinone-2H to a heme-containing protein called cytochrome c, releasing the quinone's protons in the exterior. The cytochrome's iron ion gets reduced from Fe+++ to Fe++.

Complex IV, with cytochrome oxidase, contains the final step. It takes electrons from cytochrome c, oxidizing its iron from Fe++ to Fe+++, and combining these electrons with protons and oxygen to make water. In the process, it pushes some protons outward.


So in summary: NAD - (H+ out) - quinone - (H+ out) - cytochrome c - (H+ out) oxygen to water


This process pushes a lot of protons to just outside the mitochondrion's inner cell membrane. They return through ATP-synthase complexes, complexes that add phosphate ions to AMP, making ADP, and to ADP, making ATP ( Chemiosmosis). This ATP's phosphate-phosphate bonds are then tapped for energy in a variety of cellular processes.

 

[lpetrich]

The mitochondrion's electron-transfer chain was inherited from its prokaryote ancestor, and prokaryotes show a lot of variety in their electron-transport chains, though with a similar overall structure. Wikipedia summarizes them as:

Donor -> dehydrogenase -> quinone
Donor -> quinone -> oxidase/reductase -> acceptor
Quinone -> bc1 -> cytochrome
Donor -> cytochrome -> oxidase/reductase -> acceptor


Turning to photosynthesis in cyanobacteria and chloroplasts, it is evident that it uses the same sort of electron transport. But instead of pumping protons outside the cell, the enzyme complexes live in the membranes of vesicles called thylakoids, and those complexes pump protons inward. The protons then return through ATP-synthase complexes, where they power the assembly of ATP. However, the inside of a thylakoid is topologically equivalent to the exterior of the cell.


Here are the reactions:
Water-splitting/oxygen-evolving: 2H2O -> O2 + 4H+ + 4e (H+ released inside thylakoid)
Photosystem II energizes electrons with photons
Quinone + 2H+ (from main cell body or stroma) + 2e -> quinone-2H
Quinone-2H -> quinone + 2H+ (to thylakoid interior) + 2e
Cytochrome b6f
Plastocyanin
Photosystem I also energizes electrons with photons
Ferredoxin (iron-sulfur protein)
NADP+ + 2H+ (from stroma) + 2e -> NADPH + H+
Biosynthesis processes like the Calvin cycle for fixing carbon.

Photosystem I can also cycle electrons back into the quinone, making a cycle for getting energy rather than energized electrons for biosynthesis.


Not just cyanobacteria, but also other prokaryotes can do photosynthesis. However, that capability has a rather patchy distribution among them. Early Evolution of Photosynthesis | Plant Physiology has details:

• Cyanobacteria (Terrabacteria): PS I, II ... C fix: Calvin cycle
• Purple bacteria (Hydrobacteria, Proteobacteria, in alpha- beta- gamma-): PS II ... C fix: Calvin cycle
• Green sulfur bacteria (Hydrobacteria, Chlorobi, Chlorobiaceae): PS I ... C fix: reductive tricarboxylic acid cycle (citric acid, Krebs)
• Green nonsulfur bacteria (Terrabacteria, Chloroflexi, Chloroflexus aurantiacus): PS II ... C fix: 3-hydroxypropionate cycle
• Heliobacteria (Terrabacteria, Firmicutes): PS I ... C fix: (none known)
• Acidobacteria: PS I

I've discussed this issue earlier in How photosynthesis evolved. I mentioned what may be called retinal photosynthesis there, a second kind that is mainly found in halobacteria (Archaea, Euryarchaeota).

It is evident that photosynthesis is a later development, and something built on top of already-existing systems -- electron-transfer and chemiosmotic metabolism.

 

[bilby]

 Electron transport chain -- it is an important part of energy metabolism, and it is also involved in biosynthesis. It involves sending electrons along a series of enzyme complexes and cofactors, in a series of redox (reduction-oxidation) reactions.

I note that biochemists like to call hydrogen ions protons, even though about 1 in 6400 of them are deuterons, H-2 nuclei.

That's not entirely unjustified - in biological systems, the ratio of D:H is typically lower than in the wider environment, and there are therefore more than 6,400 protons per deuteron in a cell, and often considerably more in particular molecules.

The rate of uptake of D from the environment is lower than for H, and varies across biochemicals - Proteins, for example, have a rather lower D:H ratio than smaller bio-molecules. As a result, there is a significant gradient in the D:H ratios measured in various tissues and body fluids in humans. http://iicbe.org/upload/8074C0915054.pdf

Very high levels of deuterium can be quite toxic; The risk of heavy water poisoning is, however, minuscule due to the high dose threshold and scarcity of heavy water in the environment.

You would need to drink a lot of heavy water, for a long time, in order to suffer any observable effects.

 

[lpetrich]

So I've described two main kinds of energy metabolism:

Heterotrophic:
Biological molecules -> electron transfer, chemiosmosis -> (4H) + O2 -> 2H2O

Oxygen-Releasing Photosynthetic:
2H2O -> (4H) + O2 -> electron transfer, chemiosmosis -> biological molecules

Though both sorts of metabolism are the dominant sorts of metabolism among the more prominent parts of the present-day biota, there is good reason to suspect that neither is primordial. For photosynthesis, its patchy distribution makes that rather obvious. Oxygen is also rather evidently a latecomer. It is not much used much in biosynthesis, and its major use is as an electron sink in energy metabolism. It is produced as a waste product of removing electrons from water molecules, and its production is limited to the descendants of the ancestral cyanobacterium. Some organisms do not tolerate it at all, and  Reactive oxygen species are a problem with those that do tolerate it, that make it, and that use it.

This leaves a weak form of heterotrophy: fermentation. That's long been thought of as being a primordial form of energy metabolism, because organisms could eat the primordial soup that surrounded them. Or the primordial pizza or whatever. But there are some difficulties.

Biologist Nick Lane discusses them in How did LUCA make a living? Chemiosmosis in the origin of life - Lane - 2010 - BioEssays - Wiley Online Library, also at his site.

He and his coauthors start with "Introduction: primordial soup at 81, well past its sell-by date". Regarding the RNA world, "there is currently no viable alternative to the idea", and that some parts of it are likely to be true. But RNA was likely not the first, and many enzymes use metal ions and iron-sulfur groups and the like.

Also, living things need some energy dissipation to power them, and there are no good sources of usable energy in the primordial soup. Solar ultraviolet light is not very usable, and neither is lightning.

 

[lpetrich]

Then, "Fermentation is not ‘life without oxygen’" NL et al then discuss the problems with fermentation.

• It involves some complicated reactions that do not extract much energy.
• The earliest branchers do not do it.
• Enzyme structures are different enough between Bacteria and Archaea to indicate separate origins.
• All known autotrophs get their energy from redox (electron transfer) reactions in membranes in their cells.
• Many heterotrophs also get much of their energy from such reactions.
• Fermenters often retain some chemiosmotic machinery.

The rest of the article argues for the origin of life in an alkaline hydrothermal vent. They point out that the water that goes through them gets enriched in hydrogen relative to the surrounding ocean, thus making a composition gradient. This gradient can then be tapped for energy in chemiosmotic fashion, thus becoming the origin of that sort of energy metabolism. Also, redox reactions are fairly simple, at least when compared to fermentation, and they can easily be prebiotic.

How Early Life Left Hydrothermal Vents | Origin of LIfe (2013)
The Origin of Life in Alkaline Hydrothermal Vents. - PubMed - NCBI (2016)
Hydrothermal vents and the origins of life | Feature | Chemistry World (2017)

In 1977, the first deep sea hydrothermal vent was discovered in the East Pacific Rise mid-oceanic ridge. Named ‘black smokers’, the vents emit geothermally heated water up to 400°C, with high levels of sulfides that precipitate on contact with the cold ocean to form the black smoke. This was followed in 2000 by the discovery of a new type of alkaline deep sea hydrothermal vent found a little off axis from mid-ocean ridges. The first field, known as the Lost City, was discovered on the sea floor Atlantis Massif mountain in the mid-Atlantic.

The vents are formed by a process known as serpentinization. Seabed rock, in particular olivine (magnesium iron silicate) reacts with water and produces large volumes of hydrogen. In the Lost City, when the warm alkaline fluids (45–90°C and pH 9–11) are mixed with seawater, they create white calcium carbonate chimneys 30–60m tall.

In 1993, before alkaline vents were actually discovered, geochemist Michael Russell from Nasa’s Jet Propulsion Laboratory (JPL) in California, US, suggested a mechanism by which life could have started at such vents.1 His ideas, updated in 2003,2 suggest life came from harnessing the energy gradients that exist when alkaline vent water mixes with more acidic seawater (the early oceans were thought to contain more carbon dioxide than now).

 

[lpetrich]

The rate of uptake of D from the environment is lower than for H, and varies across biochemicals - Proteins, for example, have a rather lower D:H ratio than smaller bio-molecules. As a result, there is a significant gradient in the D:H ratios measured in various tissues and body fluids in humans. http://iicbe.org/upload/8074C0915054.pdf

Let's see what might be making this big D - H difference. One may at first think that nuclei are effectively stationary, making all interaction energies electronic. But they have finite masses, and that contributes various effect. The simplest is recoil, and that makes a relative effect of about mass(electrons)/mass(nucleus), or me/mN. Vibration along chemical bonds is quantized to energies that are multiples of h*(frequency), or h*sqrt((force-constant)/mN). Quantum tunneling is even more dramatic. It gives relative rates that are around
exp( -2/hbar * integral over distance of sqrt(2*mN*(potential-energy)) )

Quantum tunneling can easily magnify the effect of different masses, producing greatly different rates. It is why alpha decay and spontaneous fission happen much more slowly than what one might naively expect. If one tries to run them backward, then the product nuclei electrostatically repel each other too much to touch. But due to wave-particle duality, they spread out enough to touch each other and combine.

Evidence that both protium and deuterium undergo significant tunneling in the reaction catalyzed by bovine serum amine oxidase - Biochemistry (ACS Publications)
Atom tunneling in chemistry | Atlas of Science
The role of tunneling in enzyme catalysis of C–H activation - ScienceDirect
Quantum tunneling observed without its characteristic large kinetic isotope effects
Quantum Tunnelling to the Origin and Evolution of Life

 

[lpetrich]

So we have the conundrum that without photosynthesis and oxygen, one is left with fermentation, with all its difficulties as a primordial form of energy metabolism. Or so it seems. But prokaryotes have been discovered that use any of a variety of inorganic electron donors and acceptors ( Electron transport chain):

• Donors: organic molecules, H2O, H2, CO, NH3, NO2-, S, S--, S2O3--, Fe++, ...
• Acceptors: some organic molecules, O2, CO2, NO3-, NO2-, S, SO4--, Fe+++, ...

I must note a bit of this in the more familiar sorts of metabolism: carbon fixation involves CO2 as an electron acceptor no matter how it is done.

What can happen is what is thermodynamically feasible. For what is, one can calculate using data on redox potentials:
 Standard electrode potential (data page)
 Table of standard reduction potentials for half-reactions important in biochemistry
Table of Standard Electrode Potentials
Oxidation-Reduction Potentials

A redox reaction is a reduction (electron sink) and an oxidation (electron source) coupled together. The amount of energy that each electron gets is (elementary charge) * (V(reduction reaction) - V(oxidation reaction)) where V is the reaction's redox potential, and since (electron charge) = - (elementary charge).

So if V(red) > V(ox), then the reaction can run spontaneously, while if the opposite, one needs something an electrolytic cell to make it happen.

Using what's in the tables, negative-to-positive ordering, for two coupled reactions, the upper reaction will want to go leftward (oxidation) and the lower reaction will want to go rightward (reduction).

Here's a simple example:
2H+ +2e- ↔ H2 -0.421
1/2 O2 + 2H+ +2e- ↔ H2O +0.816
The upper one will go leftward (oxidation) and the lower one will go rightward (reduction). That gives us V(red) = +0.816, V(ox) = -0.421, giving
V(red) - V(ox) = 1.237 V > 0
Thus, H2 + (1/2)O2 -> H2O will be thermodynamically favored over H2O -> H2 + (1/2)O2.

I've found numbers elsewhere for nitrogen oxides: Standard reduction potential of nitric oxide/ - Generic - BNID 104498 -- contains numbers for nitrogen oxides: "he standard reduction potentials for the four N-oxide couples are: nitrate/nitrite +420 mV, nitrite/nitric oxide +375 mV, nitric oxide/nitrous oxide + 1175 mV and nitrous oxide/nitrogen + 1355 mV." I must note that Wikipedia doesn't have much:
NO3−(aq) + 2 H+ +  e− ⇌ NO2(g) +  H2O +0.80
NO3−(aq) + 4 H+ + 3 e− ⇌ NO(g) + 2 H2O(l) +0.958

 

[lpetrich]

So prokaryotedom has a big world of energy metabolism beyond heterotrophy and oxygenic photosynthesis. This is the missing piece of the puzzle, because it enables organisms to be autotrophic without needing to photosynthesize. Indeed, the authors of that recent Nature conclude that the LUCA was an autotroph, making all its biological molecules as a plant does.

As an illustration, I note Bacterial Manganese Reduction and Growth with Manganese Oxide as the Sole Electron Acceptor. That was discovered for Alteromonas putrefaciens MR-1, isolated from lake-bottom sediments. This organism can use a variety of other electron acceptors if they are available: O2, NO3-, NO2-, Fe+++, S2O3--, SO3--, S4O6--, MnO2, glycine, fumarate, trimethylamine-N-oxide. However, it does not use SO4--, MoO4--, CO2.

Now for some troph terminology.

• Autotrophy - making all one's biological molecules.
• Heterotrophy - needing to consume some biological molecules.
• Lithotrophy - living off of inorganic molecules.
• Organotrophy - living off of organic molecules.
• Chemotrophy - getting one's energy from chemical reactions.
• Phototrophy - getting one's energy from light.
• Mixotrophy - mixtures of various modes: auto- and hetero-, litho- and organo-, chemo- and photo-.