What is the role of hydroxylapatite in the formose reaction and abiogenesis?

[Mike S.]

TL;DR Summary

My favorite notion is hydroxylapatite and the formose reaction. What are your thoughts?

So far, my favorite notion for abiogenesis starts with the formose reaction, which is directly catalyzed in the presence of hydroxylapatite (the naturally occurring mineral which our bodies also use in bones). A short series of steps converts formaldehyde directly into ribose with fairly good yield. Occurring in the presence of a phosphate-containing mineral, I imagine that this reaction might lead to phosphoribose, which might then react with nitrogen compounds to create a nucleotide. I'm not sure precisely how the nucleotides would emerge from a combination of ammonia, formaldehyde and perhaps carbon dioxide, but they would have a wider range than the modern four bases. Especially, consider nicotinic acid and flavin derivatives. (Folate, though somewhat reminiscent of a dinucleotide, should not be needed where free formaldehyde is available)

Besides phosphate, hydroxylapatite contains calcium ions, which chelate dicarboxylic acids - including the Krebs cycle intermediates. A reverse TCA cycle has been proposed for early life, but for this scenario I'm supposing formaldehyde gas is present in solution, meaning glyceraldehyde (a step in the formose reaction before ribose) is being fed into the Krebs cycle, and CO2 is being released as a waste product as in animals.

NADH is an RNA dinucleotide, one step beyond the RNA nucleotides already supposed to be present here. It could carry away hydrogen from the reaction. The destination would be to form lipids - specifically phospholipids bound to the hydroxylapatite substrate. That would not be a cell membrane, but a half-membrane with the hydrophobic face potentially exposed, perhaps as a "filter feeding" surface to attract hydrophobic compounds, but it would nonetheless partially enclose nucleotides and metabolites on the hydroxylapatite surface. Note that phospholipids have such an affinity for hydroxylapatite that it forms plaques on our fatty arteries.

The net reaction then might be something like 3CH2O -> 2(CH2)n + CO2 + H2O. So far as I know such a disproportionation of formaldehyde might release energy, though I haven't hunted down enough figures to be sure. Such a life form would seem to plausibly have sugars, nucleotides, and lipids -- probably no proteins unless there is free hydrogen cyanide in the environment. It might feed on dissolved gas and hydrophobic compounds, and reproduce by breaking off as a piece of membrane partially surrounding a substrate surface. It would lack a reliable genetic code, apart from some differences in the ratios of nucleotides present, but might acquire one if they begin to form bonds with one another, allowing them to extend some distance outward from the hydroxylapatite surface. What's most curious about this notion is that it seems like most of our biology - apart from the key advance of proteins - should have been established in the first day or so of living things. If it were true, then we should expect aliens might try to eat us, or provide useful nutrients, and if killed they might even leave chemically familiar skeletons behind.

How would you assess these ideas?

 

[BillTre]

The ideas you listed are good, but limited.

Since life (the product of abiognesis) is very complex, these ideas cover a small (but important) part of the complex overall picture.
Remember, there is not yet a clear and complete answer to how life arose. There are many competing explanations and different explanations for different parts of the overall process.

I would place what you are describing in a geochemistry part of the explanation. Early Earth geology provides chemicals that interact to generate more complex organic molecules.
In my view, the following issues are all involved with abiogenesis:

1. life functions as an open chemical system
2. thermodynamics involved in life (energy to oppose entropy, maintain order, and build complexity)
3. system requirements for a system to be self-sufficient (including a degree of separation from its environment)
4. individuation and the arisal of selection on groups of chemicals (such a dynamic kinetic stability in systems chemistry)
5. the history of life on Earth (such as what was LUCA (the Last Universal Common Ancestor) like)
6. history of Earth and its geochemistry
7. natural catalysts and how they became incorporated into living entities
8. the ecological position of early life/pre-life forms with respect to environmental energy sources
9. the development of trait transmitting and chemical trait production mechanisms
10. various proposed origin scenarios and sites with special properties (many have been proposed).

Any complete explanation of abiogenesis will have to address all of these issues. Its a lot of stuff. I have been focused on this for 2 to 3 years now.

 

[Mike S.]

I think my post above addressed 1, 2, 3, 8. Number 10 is the postulate. Number 5 I think is not a useful criterion - the LUCA is practically the same as us for these purposes, complete with a massive ribosomal machinery.

For #4/#9, I was suggesting a lawn of nucleotides (in a very loose sense) anchored to phosphate, which is not yet a genetic code. If they tended to dimerize via the phosphates for some reason, then they could start to form strands, and any strand would have an innate if very limited tendency to encourage RNA replication starting with another nucleotide from the lawn pairing with it. If this were sufficiently successful in the chemical environment, it could start to become a genetic code.

For #6, I'd love to hear more about where and when formaldehyde emissions could be found, and which potential dissolved gaseous precursors to nitrogenous bases are most plausible to have been present in the same environment.

For #7, I think the nucleotide cofactors would be first, but ions could creep in at a *very* early stage. For example, Ca++ positions in hydroxylapatite can be substituted with Mg++, which has a strong role interacting with modern nucleotides. Molybdenum can interact with pterins, which are closely related to the nitrogenous bases. I'd eat my hat if there were corrin rings and cobalt to bind them. And if I had a hat. :)

For #8, I'd love to hear anything about the game of CH4, CH3OH, CH2O, and CO2 in early earth. The free energies will all depend on ambient concentration among other things Is it reasonable to disproportionate CH2O to CO2 and other components in that environment?

 

[BillTre]

I don't see any explicit addressing of 1, 2, and 3. You may have been thinking about that, but I didn't see mentions of them in the post.
These issues are complex and therefore should be addressed as explicitly as possible.

Currently, my favorite scenario is the alkaline hydrothermal vent scenario. It brings togethere a lot of these issues. Alkaline hydrothermal vents are much cooler than the hydrothermal vents most people are aware of. They are the result of serpentinization reactions of sea water with newly formed (unserpentinized) basalt. This releases a bunch of chemicals to make alkaline hydrothermal vent juice (my term) which rises to the surface (ocean floor), due to its being heated (by heat released by the serpentinization process), where it comes in contact with unadulterated seawater.
Within the precipitated vent structure, interfaces between the two fluids occur across precipitated chemical walls that can also contain a variety of mineral catalysts. The opposing fluids have large pH differences and large differences in redox potential. Combined with the catalysts, many organic chemicals can be produced.
There are lots of papers and books in this.
Here is a relatively brief intro article to these issues.

The structure of the alkaline hydrothermal vents has these reactions occurring (at least to some extent) in little microchambers. This allows selection to act upon groups of chemicals (which can make things with interesting properties) as opposed to single chemicals (like nucleic acids) which by themselves are only selected for the ability to replicate. This is the power of individuation.

 

[jim mcnamara]

Thread reopened.

 

[Mike S.]

I don't see any explicit addressing of 1, 2, and 3. You may have been thinking about that, but I didn't see mentions of them in the post. These issues are complex and therefore should be addressed as explicitly as possible...

Here is a relatively brief intro article to these issues.

You raise some interesting possibilities that are not incompatible with the model above - the article also suggests that the formose reaction of formaldehyde to ribose is involved. It's true that for #1 I simply supposed there was some geological source of formaldehyde somewhere, while this model explicitly proposes the (pre) biochemistry itself generated it by reducing carbon dioxide. For #2 I supposed the formaldehyde was the energy source while the article proposes the proton motive force between vent water and sea water is used to create formaldehyde. For #3 I don't see much difference between what I said and what they say - both depend on an external geological energy source. But I have no idea what options among black smokers, white smokers, alkaline hydrothermal vents or cold seeps make the most sense.

As I was thinking of it, how the formaldehyde comes about is "external" to the abiogenesis, but of course, the boundary between "not yet alive" and "inanimate" is even harder to define than life itself. :)

The presence of greigite (iron-sulfur clusters: Fe3S4) inside vents is the most intriguing association. Besides its intermediate role in respiration, as I'm sure you know Fe3+ was what autotrophic life forms took electrons from before they were able to split water. Hydroxylapatite can precipitate in hydrothermal vents, so this could be the site for the abiogenesis, though as you say the alkaline hydrothermal vents are less violent/transient and have other biochemical advantages. The Lost City vents seem to be everyone's favorite model there. (I don't see how to square that with the suggestion your article makes about cycles of drying)

It seems to come down to a treasure hunt: where can we find the most formaldehyde, hydroxylapatite, and perhaps greigite?

 

[BillTre]

The contradictions you have noted are between different aspects of different scenarios or from what I would call partial scenarios (they solve a problem nicely, but are not obviously connected with other issues, which could be addressed).
There may be 3-5 scenarios that currently have some kind of significant support in the abiogenesis field, as I perceive it as an outsider. In the past, many different ideas have been proposed, but have been subsequently dropped for various reasons.
The article mentions more than one hypothesis. Its not always clear which idea is associated with which scenario.
This is why I am big on being explicit about these things. To reduce confusion.

Deamer's cycles of drying (which is conceptually very appealing, but limited in other ways) is (usually) associated with scenarios involving terrestrial sites (small ponds on the sides of volcanoes, rich with chemical runoff from volcanic spewings). The ponds dry up periodically and get a bathtub rings of dense crud at their edges. In this chemical mess are a mix of lipids (to make membranes) and hydrophilic chemicals. Drying concentrates the chemicals in the remnants of the vesicle. Water concentration is reduced to near zero. This reverses the mass action effect against polymerization reactions (to join nucleic acids into longer chains). These reactions produce a water molecule, which in the presence of a lot of water would be hard to produce (due to mass action).
It has also been pointed out that this change in mass action can be produced by freezing water out of solution and concentrating the other chemicals in that way.

White smokers are the alkaline hydrothermal vents.
Black smokers are the "normal" deep ocean hydrothermal vents. They are driven by the heat of recently molten rock at places of sea floor spreading. These temperatures are often high enough to destroy organic molecules.
The Lost City vent is just the first one that was found. Interestingly, these sites were predicted to exist before they were found based on the chemistry. At the same time, they were suggested as a possible site for life to orgininate before they were discovered.

Here is some some further reading, in case you are interested.

Articles:

• Russell, M.J. & Martin, W. The rocky roots of the acetylCoA pathway. Trends Biochem. Sci. 29, 358–363 (2004).
• Koonin, Eugene V. and Martin, William (2005). On the origin of genomes and cells within inorganic compartments. Trends in Genetics 21(12) 647-654
• Lane, N., Allen, J.F. & Martin, W. How did LUCA make a living? Chemiosmosis in the origin of life. BioEssays 32, 271–280 (2010).
• Weiss MC, Preiner M, Xavier JC, Zimorski V, Martin WF (2018) The last universal common ancestor between ancient Earth chemistry and the onset of genetics. PLoS Genet 14(8): e1007518. https://doi.org/10.1371/journal.pgen.1007518
• Clifford F. Brunk and Charles R. Marshall (2021). ‘Whole Organism’, Systems Biology, and Top-Down Criteria for Evaluating Scenarios for the Origin of Life. Life 11, 690. https://doi.org/10.3390/life11070690 (recent review article)

Books:

• Schrödinger, Erwin (1944). What is Life? The Physical Aspect of the Living Cell. Cambridge University Press, London, UK
• Buss, Leo W. (1987). The Evolution of Individuality. Princeton University Press, Princeton, NJ.
• Smith, John Maynard and Szathmáry, Eörs. (1995). The Major Transitions in Evolution. Oxford University Press, NY, NY.
• Pross, Addy (2012). What is Life? How chemistry becomes biology. Oxford University Press, Oxford, UK
• Hidalgo, César. (2015) Why Information Grows. The Evolution of Order, from Atoms to Economies. Basic Books, NY, NY.
• Lane, N. The Vital Question: Energy, Evolution, and the Origins of Complex Life (WW Norton, 2015).
• Luisi, Pier Luigi (2016). The Emergence of Life. Cambridge University Press, NY, NY
• Deamer, David. (2019). Assembling Life; How Can Life Begin on Earth and Other Habitable Planets? Oxford University Press, NY, NY.

There are many more articles and books.
Brunk and Marshall say there is

a huge literature—a Google Scholar search from 2001– 2020 for ‘origin of life’ yields 25,400 results. While we are not concerned here with life elsewhere in the universe, we note that the burgeoning field of astrobiology has also injected enormous energy into the study of the origin of life, with 119,000 Google Scholar search results from 2001–2020.

Since I am no longer associated with a university, I find copies of articles either by googling them (by article name), or finding them in Academia or Research Gate, websites that distribute reprints.
In addition, some researchers (like Nick Lane) have their own websites with their publications for download.

 

[Mike S.]

This is a terrible, terrible time to be getting new literature cites I'd like to read. I'm feeling too nervous that Sci-Hub will be a casualty of out of control politics, or co-opted in the cyber war. I could say that if we leave that site to the Russians, they'll be smarter than us because they can do such convenient interlibrary loan, but that wouldn't really be accurate -- they'd be smarter than us for standing up for their right to read and talk about science in the first place.

 

[BillTre]

Well, to try to get your mind off your troubles:

Number 5 I think is not a useful criterion - the LUCA is practically the same as us for these purposes, complete with a massive ribosomal machinery.

You are correct that LUCA is in many ways quite similar to us. The whole translation mechanism (ribosomes, tRNAs, aminoacyl transferases (enzymes to put the right amino acids on the right tRNA), as well as the Signal Recognition Particle system (put the right proteins through the membrane), and an encoding mRNA) as well as significant proteins involved in metabolism (the electron transfer chain and the membrane ATPase (driven by a proton (H⁺) turbine) is shared universally and therefore thought to have been present in LUCA.

This indicates that LUCA is indeed quite complex. That should not be over looked.
However, a closer look at LUCA's capabilities is reveals things about its interactions with its environment.

LUCA's metabolism is thought to have collected its energy from an environment that was similar to alkaline hydrothermal vents (it had or was similar to a H₂ based metabolism).

LUCA did not yet have encoded proteins for DNA synthesis, although it had DNA. (the DNA synthase function must have been done by something else, like ribozymes.) Encoded enzymes for these arose independently in the bacterial and archaeal lineages. Bacteria and archaea are the two lineages that came directly from LUCA, and which therefore define it phylogenetically. They are LUCA closest relatives.

LUCA lacks traits that might allow it to survive stressful environments (environments different from those in which it arose).
It lacks encoded enzymes for synthesizing membrane lipids, even though the whole ETC and membrane ATPase system relies on membranes for its function. These enzymes arose independently in the archaea and bacteria. Membrane molecules must have been produced in some way, in LUCA, for the encoded metabolic proteins to have evolved.
Same story for their cell wall components (more robust containment then just a cell membrane). They arose independently in bacteria and archaea.
In addition, bacteria move around by spinning their flagella. This gives them increased environmental mobility (a way of ntiieracting with their environment). Archaea have an equivalent, but different, independently derived structure, the archella. This implies that LUCA had neither, and was therefore not as well adapted for moving around in its environment, as the archaea and bacteria were.

 

[Mike S.]

Interesting ideas there! Some don't grab me at face value though. It seems orthodox to suppose DNA was a latecomer to genetics. The difference in metabolism sounds like it should be expected from a reducing atmosphere. The flagellae ... I'm not so sure. I mean, just because Archaea has A and Bacteria has B doesn't mean that the original X was zero. It might be that one lineage adopted a new flagellum, or both dramatically diverged from some less efficient composite.

But the lipids -- *that* is a key mystery to figure out for abiogenesis. The cell membrane defines the cell, and the lipids themselves are different in Archaea and Bacteria. Our own love-hate relationship with cholesterol dates back to that, I think. Now I was assuming phospholipids were ancestral because they stick to hydroxylapatite, but I don't really know that. The isoprenoids can press their own claim to the throne, being built up from G3P and pyruvate, which seems to get very close to the putative formose reaction at the moment of abiogenesis. There have been multiple hypotheses ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244643/ ), and I haven't put in nearly enough effort to understanding the situation.

 

[BillTre]

The flagellae ... I'm not so sure. I mean, just because Archaea has A and Bacteria has B doesn't mean that the original X was zero. It might be that one lineage adopted a new flagellum, or both dramatically diverged from some less efficient composite.

This kind of thing is always possible.
However, from a phylogenetic view, the scenario (or hypothetical relationship) requiring the fewest changes is the favored hypothesis.
Of course, this doesn't rule out alternatives, just makes them seem less likely.

The scenario of making one of flagella or archella (1 change), diverge to two taxa, make the second of the motility structures (2nd change), get rid of one (3rd change), maybe (depends on scenario details) get rid of the other one in the other taxon (possible 4th change).
Alternatively (with fewer changes): diverge the first two taxa, Make one (1 change), make the other (2nd change).

 

[Mike S.]

Parsimony has its place, when there's no particular reason for something to happen (neutral mutations). But I've noticed a strong tendency of research models to underestimate the complexity of common ancestors. This goes to ridiculous extremes sometimes - people who postulate that Melanesians got to Australia without boats, or that urbilaterians didn't have eyes or a nervous system. In this instance, we know bacteria can have two entirely different sets of genes for flagellae ( https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4481668/ ). Given the strong selective push to invent a faster engine, and the multiple roles of flagellae in different environments, biofilms, etc., I'm not going to assume a parsimonious model.

 

[BillTre]

Given the strong selective push to invent a faster engine, and the multiple roles of flagellae in different environments, biofilms, etc., I'm not going to assume a parsimonious model.

Exposure to different environments, biofilms etc. would presumably all happen later in evolution, after simpler survival requirements of just getting by have been fulfilled.

The parsimony argument is made stronger by the fact that the flagellum and archellum are each composed of several different proteins. Each of the proteins requires a separate and independent changes when the gene was formed. This would increase the number of changes required to produce the observed complex result.

I've noticed a strong tendency of research models to underestimate the complexity of common ancestors.

LUCA is the best known of the common ancestors, but there would be a long series of earlier ancestors (the earlier that Last Known Common Ancestors) extending back into more ancient times. Many of these would be reasonably expected to be simpler than those that come after, since life originated from non-organized non-life chemicals. When you start from zero organization, there is only one way to go.

Here is a recent, open source review of the flagella/archella issues:
https://www.cell.com/current-biology/comments/S0960-9822(18)30151-9

 

[Mike S.]

That's a nice review, though it leaves many questions unanswered. It describes archaella as the homologues of type IV pilin of bacteria and archaea, which pulls out some useful articles ( https://www.frontiersin.org/articles/10.3389/fmicb.2015.00023/full https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510520/ ). This is a versatile family of proteins, with some unknown as of 2015 mechanism for transferring themselves out of the cell, it looks like. Problem is, they can do so many different things besides propulsion, from DNA transfer to twitching motility to adhesion, it's hard to know what was first. We know LUCA had them but what it did with them is another question. Still, if I had to guess an an activity type IV pilins could have lost during evolution of one lineage, why not the motility pattern that was reinvented using other proteins?