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Comment by mtdewcmu | Hacker News Reader

The hypothesis that goes something like

RNA bases -> RNA -> proteins -> life

seems to sidestep the issue of metabolism, i.e. what did the first organism eat? What was its energy source?

When I picture life arising from nothing, the most plausible scenario seems to involve increasingly intricate chemical reactions that initially do absolutely nothing other than create longer and longer staircases for energy to step through through before dissipating and becoming useless. In other words, you start with metabolism first, and then get structure later.

It seems plausible that the earliest proto-metabolisms didn't use RNA or resemble modern life in any way. There might have been a succession of proto-metabolisms before getting to anything we would recognize as life. They would likely not have left any fossil record.

Does this make any sense to anybody?

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Sure, you could start with metabolism first, and then get structure later. But you can narrow it down even further by saying this: you start with self-replication, and everything else comes after. Evolution stems from self-replication. This is why RNA, of all the things we know, is the best candidate for the origin of life. The smallest self-replicating RNA is relatively small and simple, and can arise spontaneously and mark the beginning of evolution, given the right environment. The separation of structure and metabolism doesn't even exist yet.

The fact that a self-replicating RNA could have arisen given what we know of primordial earth is extremely convenient. Something different and unknown could have come first, but it would have to fit the bill of "can arise spontaneously" and "can self-replicate and pass down incremental modifications", which is very difficult to pull off. We also have good certainty that LUCA (last universal common ancestor) featured RNA.

I will also try to answer: what did the first organism eat? The concept of food/energy source doesn't apply so well to the first self-replicating RNA. The environment features constantly interacting bases, and the competition between self-replicating RNAs stems from this. The distinction between individual organisms and the environment isn't as clear-cut as what we know now. Through this competition, one of the first things to be acquired was probably a membrane. Eating can become possible and/or useful after you have a membrane, which also allows you to extend the environment in which you can thrive.

I went through several different ways to approach responding to your comment before writing this version. I think this is most succinct.

Self-replication can itself be viewed as a metabolic process. You really can't have replication before metabolism, because replication is metabolism. The question is which metabolic process came first.

Since replication is anabolic and requires an energy source, it seems like it makes sense to deal with energy first.

You can have reactions that harness energy to do nothing useful -> reactions that harness energy to cause self-replication -> life.

>I went through several different ways to approach responding to your comment before writing this version.

I also edited it quite a bit (but now I'm done, promise...) One of my points is that replication does not require a separate energy source, in the right environment. RNA is highly reactive given the right temperature and conditions, this is why all modern life does not use it as permanent storage medium (this also makes it very difficult to work with in the lab). Only replication of a DNA-based life form strictly requires a control mechanism and energy source.

>> One of my points is that replication does not require a separate energy source, in the right environment. RNA is highly reactive given the right temperature and conditions,

I actually don't know what a flask full of RNA will do when left to its own devices. My science education has gaps. However, really basic chemistry says that you can't create big molecules from small molecules without some sort of energy gradient, because the big molecules have less entropy than the small ones.

When you have a flask full of stuff, what it does spontaneously is go to thermodynamic equilibrium. If you want a self-sustaining reaction that creates specific big molecules over and over, you need to keep adding energy.

Fortunately, Earth is located near a huge fusion reactor, and comes equipped with its own auxiliary internal fission reactor. There was plenty of energy gradients in the environment then, the same way there are now.

Why isn't the following chain plausible?

Chemical compound soup, natural reactions -> natural reaction produces the first reaction which is self replicating (I'd assume RNA here) -> self replication reaction dominates natural reactions (to what order, who knows) -> self replicating reaction mutates into a form that better harnesses energy from environment (your metabolism) -> metabolic empowered reaction dominates -> etc

From a primatives perspective, it seems reasonable that the first "evolutionary" advances would have all been incredibly preferential. In the sense that they had no competition with similar capabilities.

Imagine the first organism able to metabolise something (sunlight?) for its own purposes. Against "organisms" that were still waiting for chance to bash them against the right compound.

I wrote out the mechanism that I'm proposing down lower, and I'm going to paste it again up here so that people see it.

My idea of how Metabolism First would work is something like this:

1. You get a lot of weird chemistry happening, say, in pools of water. This chemistry starts creating large organic molecules that are like sludge building up in the pools. These molecules are dead, but they are rich in energy and perhaps interesting building blocks. Maybe they are made of amino acids.

2. Now you have this unbelievably rich energy source, and at some point there start appearing chemical chain reactions that start "eating" the sludge.

3. Life originates from these chemical chain reactions.

I suppose it kind of flips the prevailing hypothesis around. Rather than have lightning and such build our proto-organism directly, instead it builds up a sludge that the proto-organism eats.

With the planet being sterile, this organic sludge could build up forever until something figures out how to eat it.

> The smallest self-replicating RNA is relatively small and simple, and can arise spontaneously and mark the beginning of evolution, given the right environment.

Do you have a source? If by small you mean 100+ bases it has little chance of arising spontaneously. The article speaks only to the possible spontaneous formation of building blocks, not of them assembling into complex forms.

One of the suggested possibilities is that there was a pre-RNA molecule, such as PNA[1]. PNA is less efficient but it's much more durable, simpler to form, and can self-polymerize above boiling. If you had enough PNA in one place and got it relatively hot, it would spontaneously form "genes" which would be stable for an extremely long time. They would just float around, and any time they came into contact with enough PNA they would be able to replicate. It would be a relatively slow process, but purely random and so would quickly gravitate towards optimization.

RNA can do the same thing. Transcriptase and polymerases are catalysts but they are not strictly necessary. Simple RNA can have a lifespan of hundreds of years and it just needs to replicate more than once to propagate. Over time a primitive polymerase would eventually be made by freak chance and mutation, and then everything would kick off.

Once you have polymerase natural selection would speed up massively and become resource-limited rather than reaction-limited. Thats when a metabolism would evolve, and enzymes that were successful at catalyzing the conversion of material into resources would stimulate local growth. You'd still only have a frothy mess of chemicals, but it would be a frothier mess than the surrounding mess. The first organism to make some kind of container wins- most likely they'd evolve mucus-y proteins that would help keep their resources concentrated. Over time that mucus would give way to a hollow bubble, which would then become a lipid layer, which would then become the first cell.

[1] https://en.wikipedia.org/wiki/Peptide_nucleic_acid

I think the fundamental problem is that a strand of PNA floating in water is just a strand of PNA floating in water. It isn't an organism, because organisms do things, things that require inputs of energy. I don't see how this lonely strand of PNA ever figures out how to spontaneously give itself a metabolism. Without having a metabolism to begin with, that PNA strand will never do anything.

The metabolism is to simply wait for resources to react naturally. PNA in sufficient concentrations and conditions will continue to polymerize and grow just by random chance. It's not any different from what happens inside a simple cell, really: ATP and other resources are for the most part just present inside the cell. It's just that for life to come about those conditions or something like them have to exist naturally.

As the RNA/pre-RNA chain grows, there will be natural selection for any sequences that catalyze polymerization. This will eventually either lead to self-catalyzing replication or a mutual replication. AFAIK the second one is considered more likely because although RNA can self-catalyze it's not very good at it (of course, it doesn't really need to be). Mutual replication would require a primitive polymerase being spontaneously generated, which would allow an RNA-like molecule to -self-replicate. Eventually an chain would be created that could replicate via copies of itself, and that molecule would be able to spread beyond the original catalyzing molecule and outcompete anything else (since it would be able to replicate with any copies it made, it would grow exponentially rather than linearly).

My proposal is basically that the proto-organism has to learn to eat before it can do anything else. The processes that you have described could still have important roles to play.

You may be looking for the RNA world hypothesis [1] [2]. In essence, random bits of RNA combine and replicate "in the wild". The bits that replicate better become more prevalent, et cetera, et cetera. This system needs no metabolic process per se. Heating and cooling and/or an oscillating chemical environment , e.g. from the day and night cycle or the tides or a belching vent, could provide the energy to power these cycles.

[1] https://en.wikipedia.org/wiki/RNA_world

[2] https://www.youtube.com/watch?v=K1xnYFCZ9Yg

Hmm. I could see the day-night cycle as creating the large molecules of organic junk that the life, or proto-life, springs from and eventually eats.

It seems like having big molecules of junk lying around would set the stage for self-replicating processes to be able to "eat" the junk molecules and put the energy into synthesizing its own molecules.

It makes perfect sense to me. There is indeed a division between the metabolic first hypothesis, which posits the spontaneous assembly of autocatalytic metabolic networks under the correct conditions (lots of incoming useful energy + abundant simple molecules for autocatalysis). The problem with this view is it doesn't realistically allow for natural selection (even putting aside the difficulty of achieving a biochemically plausible cycle in early earth conditions). The replication first hypothesis allows for natural selection but in turn faces the problem of how the raw material of sufficient complexity (nucleotides) to allow reliable template based synthesis could have plausibly come about. The linked to article addresses one hypothesis for one possible path for arriving at the building blocks of RNA given that early conditions were close enough to its assumptions.

I enjoy works which look for scenarios where both could have emerged simultaneously. Reading the introduction of this paper/article provides an accessible exposition to the topic: http://www.mdpi.com/1422-0067/10/4/1838/htm

If you are curious about under what conditions self-organization might more effectively dissipate entropy I suggest reading anything by Ilya Prigorine. But this short minute physics video narrated by Sean Carroll is good for a start: https://youtu.be/HxTnqKuNygE?t=2m07s

I don't see self-replication as being the hard part. Once you have enough complex chemistry going on, self-replicating processes will appear spontaneously like contagious diseases. I'm thinking of, e.g., prions, which self-replicate, but they are not life -- they're just screwed-up proteins that happen to screw up other proteins in exactly the same way they themselves are screwed up, thus making more of themselves. There are also plasmids, which don't really resemble anything like life, yet they self-replicate. Self-replicating things pop up randomly in strange places and they are amplified through positive feedback.

The hard part seems to be getting to the point where the chemistry is so complex that self-replicating things are even possible.

Deep sea vents provide a lot of chemicals that can be broken down for energy. There are currently entire ecosystems based on this. (https://en.wikipedia.org/wiki/Hydrothermal_vent#/media/File:...) So, early earth was likely awash in chemical energy for life. https://en.wikipedia.org/wiki/Hydrothermal_vent

You may be interested in this article, which espouses a similar idea that life is a mechanism for more efficiently dissipating energy, and thus a natural consequence of a universe following the Second Law of Thermodynamics: https://www.quantamagazine.org/20140122-a-new-physics-theory...

(disclaimer: the article is quite handwavy, but could be a good jumping-off point if you so choose. Sounds dubious to me but interesting to consider)

Life seems like a very inefficient way to dissipate energy. And that's kind of the point, you need to hang onto the energy long enough to do something with it before it dissipates.

The most efficient way of dissipating energy seems like it would be something like

Photon comes in -> photon reflects off water -> photon goes back out to space

Life is pretty good at entropy. Take for example: humans. We've been digging up vast amounts of fossil fuels to then burn them up. Without us, those reserves would stay in the ground probably forever. Is there another organism that's better entropy as us? (actually I think there are contenders)

Perhaps that's our reason for being.

We are just a different, temporary state of the same stardust, as everything else around us — as in, a small part of the Universe transformed into us, then started trying to understand the rest of itself. :)

"Reasons" are human constructs. We don't need a reason to be, we just are.

Eh, but it makes sense we still follow the Second Law of Thermodynamics, right? When people ask themselves, "What's the point of Life?" That's it: We're agents of entropy.

There's nothing that makes that the point of life, though. It's just a fact about it. Just as it is equally a fact about non-life.

As a layperson, I've no opinion on this – just sharing the article because it seemed amenable to your idea that life emerged non-acutely as a natural consequence of physical laws.

> Life seems like a very inefficient way to dissipate energy

It seems like a good way to dissipate complex energies. Chemicals pouring out of deep sea vents contain lots of chemical potential energy, but it's difficult to unlock without a complex mechanism. Life unlocks those mechanisms. Taking it several steps further, a uranium-powered particle accelerator produces massive amounts of complex entropy.

Relevant article:

http://bytesizebio.net/2009/10/11/weekly-poll-replicators-fi...

"Replicators First

Aka RNA World: RNA emerges as the first molecule that can replicate and perform enzymatic processes. It stores information and it is biochemically active. Thus it can both replicate and control a primitive meabolism. Later came the transition to DNA as an information storage, and the enzymatic role was mostly relegated to proteins.The first replicators might not even have been RNA molecules, but some pre-RNA nucleic acid such as PNA or TNA..."

"Metabolism First

Metabolism First holds that metabolic processes assembled prior to the existence of replicators. Günter Wächtershäuser proposed that the pioneer organism originated in high (>100C) temperatures in hydrothermal vents. This organism resembled the catalytic converter in a car, more than a primitive cell: it had a composite structure of a mineral base with catalytic transition metal centers, such as iron-sulfide and nickel-sulfide... "

How about antagonistic roles for each? They may have existed independently, but joined a feedback loop where the metabolic process draws energy from a replicating process ... or chain reaction of RNA syntheses was the metabolic and replicating process both at once. How about it?

Metabolism First and RNA World are two competing hypotheses that have both been around for a long time.

Here's a nice recent review of the field:

https://www.nature.com/articles/s41570-016-0012

It's hard to have an idea that's completely unique. It actually makes me feel better if there's a precedent, because that's an indication that the idea makes some sense. It's possible that I encountered the MF hypothesis previously and forgot, but it entered into my thinking somehow. I'm really cautious about claiming to have a unique idea without having verified it.

The idea of how MF would work presented in the article sounds really implausible.

My idea of how MF would work is something like this:

2. Now you have this unbelievably rich energy source, and at some point there start appearing chemical chain reactions that start "eating" the sludge.

3. Life originates from these chemical chain reactions.

In that article, their version of MF seems to require high energy. Mine happens under gentle conditions.

I think that's the whole of my idea.

@jonathansizz Thanks for posting. I have a technical background but very little education in chemistry or biology. Can you or anyone else here recommend some resources for learning the basics of biochemistry and evolutionary biology?

The real 'sidestep' in the Base/RNA/Protein/Life theory is the lack of transcriptase and ribosome equivalents. Some theories posit that ribosomes were exclusively RNA-based and developed the ability to self-transcribe at some point. To give a sense of how impactful this would be, if accurate, the central dogma of molecular biology is shown to be fundamentally wrong.

----

Going from a string of RNA to another string of RNA is no easy task. Additionally, going from RNA to a protein requires more than just energy. It requires a molecular factory which can commence protein synthesis.

This requirement is somewhat mitigated by the fact that RNA itself can fold in on itself to form useful structural elements, albeit far simpler than protein-based chains.

>> Going from a string of RNA to another string of RNA is no easy task. Additionally, going from RNA to a protein requires more than just energy. It requires a molecular factory which can commence protein synthesis.

If you're starting from something simple that already works, you can imagine how it might evolve into something more complex in small increments, with the new stuff gradually replacing the old stuff until the old stuff is completely gone.

The important thing is that you start with something that already works.

That's why I'm proposing that you start with some kind of self-sustaining chemical reaction, i.e. a metabolism. If you start with a dead strand of RNA, it's hard to imagine how a metabolism springs up spontaneously around it and suddenly starts doing anything at all, much less anything useful like making proteins.

Did there have to be any eating?

Imagine a simple chemical chain reaction, where RNA is floating around in the "primordial soup", and self-replicates simply when it encounters the molecules needed to do so.

RNA is just a chemical, you don't need a whole organism for it to float around and react with other chemicals.

Of course, maybe these two things happened at the same time. Maybe mitochondria developed as the dumb metabolic engine, while RNA developed into the structure. Eventually the structure captures metabolic engines to fuel it directly, rather than harvesting free chemical energy from the environment.

"Did there have to be any eating?"

Define "eating".

"and self-replicates simply when it encounters the molecules needed to do so."

It self-replicates, destroying those molecules. One could call that "eating", and probably should, as, if one calls this self-replication, there's an underlying assumption that there is life.

Why does it necessarily have to be one or the other? Is it not plausible that there were replicators and metabolizers forming in tandem?

And then at some point they got together and both replicated and metabolized.

You should consider reading "The Vital Question" by Nick Lane. Bill Gates strongly recommended it in one of his Gates' notes. It is an exploration of the central role that energy/metabolism has had in the initial formation and continued evolution of life. A subtext in the book is how biologist have been so fixated on the "information" side of evolution (DNA/RNA) they've overlooked the massive importance of metabolism.

Most intriguingly the book presents an extremely specific and extremely plausible theory for the very beginnings of life. i.e., resolving the questions: Was there a cell before there was metabolism? Or conversely, what is metabolism before there is a cell?

I don't know much about this stuff, but I'm curious - do viruses and prions metabolize? Seems to me that "early life" would be exactly like what your OP said - just replication. Replication leads to replication, eventually the better replicators replicate more, etc.

It does make sense to me. It kinda reminds me of Process Philosophy too.

Good comment, but I'll nit-pick this statement:

> When I picture life arising from nothing

Please don't. Life didn't arise from nothing. That would be like saying "When I picture a supernatural entity creating life".

The rest of your post sounds interesting though. Can't comment on that, not my field.

I think the parent meant it more like, life arose out of no-life.

Or in othet words, there was "stuff" that wasn't alive and then something happened and life was formed. Instead of "there was this absolute void thennlife was formed".

I know. I know. That's why I called it a nit pick. Judging from the down votes I guess people don't have a sense of humor. It's OK. People gotta chill.

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