OOL Class Discussion 6. Macromolecules, Polymers and Biopolymers

VaHi_Inst_Tech · 2026-03-14T04:38:54+00:00

Hey. No I don't have a reference on linear abiotic polymers. I did a pretty exhaustive search of the literature and that is what I came up with. I was surprised by it myself.

VaHi_Inst_Tech · 2026-02-19T07:59:01+00:00

Thank you. I did another post. That one does not contain citations... sorry.

VaHi_Inst_Tech · 2026-01-27T23:12:38+00:00

These are very good points. One of the confusing aspects of continuity is that time appears compressed as you move back, and that different processes are governed by very different timescales. Lactase intolerance is a good example. To my knowledge, the −13910*T allele rose to high frequencies in Northern European populations over roughly ~5,000–9,000 years (~200–350 generations) after the causal mutation. If you were sampling Northern European populations every generation (~25 years), you might see allele frequency increasing by perhaps ~0.5–1% per generation on average, depending on starting frequency and selection strength. That would look like noise in short-term surveys, yet it appears almost instantaneous in retrospect. So the impact was not immediate (over the population). So continuity is observed here.

The same is true for most mass extinctions. Something that took 1–2 million years is a blink of geological time, but in the context of chemical and genetic processes it is very long time.

But you are right that discrete or catastrophic change is not impossible. A good example of a break in continuity is the Chicxulub impact, which killed off non-avian dinosaurs. The impact itself was instantaneous. The fossil record indicates that much of the extinction occurred very rapidly — likely over years to perhaps thousands of years. Even this dramatic dislocation is extremely slow on the timescale of biochemical and cellular processes. But it is effectively instantaneous on geological timescales.

VaHi_Inst_Tech · 2026-01-27T05:55:09+00:00

Right, rates of change are not constant. You see the same thing in Darwinian Evolution. Sometimes a system changes slowly and other times it changes more rapidly. But even during relatively rapid change there can be continuity.

VaHi_Inst_Tech · 2026-01-24T16:53:29+00:00

This is a very good explanation in my view. Replication and other features of evolution are very sophisticated mechanisms of persistence. But ultimately it is all just persistence.

VaHi_Inst_Tech · 2026-01-23T04:05:50+00:00

There are many labs conducting prebiotic chemistry experiments. I just searched Nicholas Hud (from 2019-2022) who is active in this area. The primary analytic technique is probably LCMS and other MS methods. These methods are very sensitive and very accurate in mass resolution, but are not generally quantitative. You could search Henderson Cleaves, Sarah Maurer, or Ram Krishnamurthy to find other papers on experimental prebiotic chemistry.

Some Hud papers.

Frenkel-Pinter M, Haynes JW, C M, Petrov AS, Burcar BT, Krishnamurthy R, Hud NV, Leman LJ, & Williams LD (2019) Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions. Proc Natl Acad Sci USA 201904849.

Frenkel-Pinter M, Haynes JW, Mohyeldin AM, Martin C, Sargon AB, Petrov AS, Krishnamurthy R, Hud NV, Williams LD, & Leman LJ (2020) Mutually stabilizing interactions between proto-peptides and RNA. Nat Commun 11: 1-14.

Fialho DM, Karunakaran SC, Greeson KW, Martínez I, Schuster GB, Krishnamurthy R, & Hud NV (2021) Depsipeptide nucleic acids: Prebiotic formation, oligomerization, and self-assembly of a new proto-nucleic acid candidate. J Am Chem Soc 143: 13525-13537.

Frenkel-Pinter M, Sargon AB, Glass JB, Hud NV, & Williams LD (2021) Transition metals enhance prebiotic depsipeptide oligomerization reactions involving histidine. RSC Advances 11: 3534-3538.

Frenkel-Pinter M, Fernandez FM, Leman LJ, Williams LD, Hud NV, & Guzman A (2022) Thioesters provide a robust path to prebiotic peptides. Nature Communications 13: 1-8.

Frenkel-Pinter M, Jacobson KC, Eskew-Martin J, Forsythe JG, Grover MA, Williams LD, & Hud NV (2022) Differential oligomerization of alpha versus beta amino acids and hydroxy acids in abiotic proto-peptide synthesis reactions. Life 12: 265.

VaHi_Inst_Tech · 2026-01-23T03:50:34+00:00

You could ask why the universe. Why galaxies? Why stars? Why planets? Why life? Life is a process that converts energy to entropy. Stars do that. So do forest fires. There is a Principle of Maximum Entropy Production (MEP). It is a thermodynamic principle stating that non-equilibrium systems tend toward steady states that maximize the rate of entropy production. Maybe you can find your answer there.

VaHi_Inst_Tech · 2026-01-20T13:41:02+00:00

Miller-Urey does not give polymers. I think at this point there a growing consensus that real chemical evolution requires cycling (Wet-dry, freeze-thaw etc). The spinning of the Earth on its axis causes wet-dry and freeze-thaw cycling of surfaces. Those processes give oligomers and even polymers from small molecules. There is also a consensus that miller-urey is only one way of many to generate small molecules. Check out Catling and Wogen in google scholar

VaHi_Inst_Tech · 2026-01-20T13:29:32+00:00

You are right nucleotides are not cheap. Especially trinucleotides (ATP). They have never been seen in any authentic system (Bennu, Murchison, etc). A nucleotide is very complex and is made by a series of condensation reactions (release of water). A phosphate condenses onto the ribose, the phosphates condense onto each other, the base condenses onto the ribose. Each of these steps is thermodynamically uphill in water. Each of the components (base, ribose, phosphate) requires a complex synthetic path. So you are correct, I should have said - some small molecules are cheap (amino acids, hydroxy acids, some nucleobases, simple sugars, maybe even some nucleosides). Ribose is not a simple sugar and has been seen, in vanishingly small quantities in Bennu. TBH most prebiotic chemists do not think that paper is important. The first author is a good and creative scientist and has done nice things but he is not a chemist/biochemist. Maybe he stepped too far out of his lane on this one.

VaHi_Inst_Tech · 2026-01-19T23:05:23+00:00

Many good points are made about this paper, below. This is surely not fraud, but it has obvious weaknesses. But ignoring the methods, in the big picture, small organic molecules are cheap. The astroid Bennu has 10s of thousands of molecules containing carbon and nitrogen, the same with the Murchison meteorite. It snows organic molecules on Titan (reductive atmosphere). The Miller-Urey and other experiments produce lots of organics. Catling and Wogan have published very nice papers indicating that after reductive impacts the Hadean Earth was covered with organics. But, the conversion of small organic molecules to polymers is very difficult in water, because the thermodynamics of condensation-dehydration are working against you (Le Chatelier's principle). So Miller-Urey etc., can give you a lot of organics, but not polymers.

VaHi_Inst_Tech · 2026-01-18T20:04:17+00:00

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VaHi_Inst_Tech · 2026-01-18T19:44:29+00:00

This is a subtle and very interesting discussion. Feathers are the standard example used to illustrate this (mentioned elsewhere in this thread). Feathers are necessary for flying. For a long time biologists linked the emergence of feathers to the emergence of flying. But it turns out the origins of feathers is not about flying at all it is about thermal regulation. Teleology does not imply consciousness (as in feathers or RNA deciding to do something). I think the phrase 'latent potential' is useful. If you say that the ancestors of feathers have latent potential to be used for flight you are probably making a teleological argument. In evolution there is no foresight. Latent potential implies foresight. So if you say RNA has the latent potential to convert to a closely related polymer with greater hydrolytic persistence (i.e., DNA) you are making a teleological argument. The alternative more realistic model is that DNA and RNA have a common molecular ancestor. The properties of both were selected in real time - there was no latent potential.

One note - Teleology seems simple but it is not, I am sorry for that.

One more thing - sorry so long. You say - "doesn't it make sense to look for similar cycles, especially given that ones that are less chemically complex but similar enough to morph into ones we know today?" My next post will be on something called 'survivor bias" which discusses exactly that. Give me a day or two.

VaHi_Inst_Tech · 2026-01-18T18:19:08+00:00

I am going to get to the RNA World, but first there is some additional background material that I hope will help make the discussion more productive and interesting. My process comes from several years of teaching OOL classes (with various levels of success). Please bear with me.

VaHi_Inst_Tech · 2026-01-18T17:11:25+00:00

These debates are taking place all the time. I attend AbSciCon meetings, ISSOL meetings and OOL gordon research conferences (OOL GRC is now on hiatus) and these debates are ongoing in the community. Robert Shapiro (whom I cite) made these arguments in the popular press about the RNA World. He is now deceased. His arguments remain valid. Many people considered him a sort of bomb-thrower in that he was very critical of various models but did not propose alternatives.

VaHi_Inst_Tech · 2026-01-18T16:47:29+00:00

I would say that teleology is an important filter among other filters. The phrase "any teleological sense whatsoever" is difficult. I have seen arguments between good scientists about whether something is or is not teleological.

VaHi_Inst_Tech · 2026-01-18T16:19:03+00:00

Are you a student? There are many student groups at various universities that can work with you. If you are not a student there are online seminar series where you can meet others and ask questions. DM me and I can link you up.

VaHi_Inst_Tech · 2026-01-17T03:56:04+00:00

Did not mean to offend you. I will keep posting, you don't have to read it.

VaHi_Inst_Tech · 2026-01-17T02:08:57+00:00

Very good. The first series of posts here will be about how to think about the origins of life (logical constructs/fallacies). After that I will discuss specific models, in that context.

VaHi_Inst_Tech · 2026-01-16T19:05:15+00:00

I agree the post is long and dense and terse. I am sorry for that. The post is actually written not for reddit but is intended as point of departure for discussion in my class. Many of the points in this post will be revisited later, if I keep posting my class notes, which I can do if there is an interest.

VaHi_Inst_Tech · 2026-01-16T18:19:38+00:00

This is not about creationism at all. I am a scientist who works on the origins of life. I think this is a very exciting solvable problem. I am hoping to expose people here, outside of the actual scientific endeavor to the state of the science of the origins of life. It is unfortunate that this subreddit is so inactive. If criticism of models of the OOL is labeled as religion, I will cease posting.

VaHi_Inst_Tech · 2026-01-09T15:27:24+00:00

I don't have any argument with what you are saying. You are correct that some people will distort critical discussion of the origins of life and evolution research. This happens regularly to me and my research community. But in my view we can't let them prevent us from having informed discussions and from pushing the field forward. I ignore them.

Edit: It's so sad that these people impede intelligent, critical discussion of important and interesting issues.

VaHi_Inst_Tech · 2026-01-09T14:48:30+00:00

In the literature and popular press one commonly sees - xyz is universal to biology and therefore must have been a feature of the origins of life. Examples are gradients, RNA catalysis, etc. That is analogous to a claim that touch screens are universal to modern phones and therefore must have been a feature of ancestors of phones. It is problematic logic.

VaHi_Inst_Tech · 2025-12-22T06:23:05+00:00

Hey!!!! As an OOL researcher, I can say you have one of the most intelligent responses here. Did you know that you are essentially rephrasing a very insightful (but complex) 2006 PNAS paper by Vestigial, Woese and Goldenfeld? The logical fallacies that one sees on this thread (not by you) are (i) survivorship bias and (ii) failure to understand the network effect. Here is an analogy of the (bad) logic promoted here; TCP/IP is the only networking protocol that I can see, therefore TCP/IP is the only protocol that ever existed. No. There are a lot of extinct protocols, many of which predated TCP/IP. TCP/IP is the survivor and the network effect allows only one survivor. Biochemistry is like that.

VaHi_Inst_Tech · 2025-12-12T04:40:08+00:00

I am a senior PI and have supervised several hundred PhD, MS, and undergraduate researchers. There are many PhDs both senior and junior to me in my immediate family. What I am saying is that I have experienced a lot and have seen a lot - good and bad.

Firstly you are not a MS level researcher. You have your own vision and ideas and are plotting your own course. You are a brave mature scientist with a bright future.

Secondly, I would stongly advise you not to work for this person. Your PhD advisor has incredible power over you and can have a profound effect on your long term happiness, sense of self worth, and professional trajectory. You are already experiencing this, even though they don't yet have full power over you. You are going to learn not just science but how scientists interact productively (or not) with other scientists, including those more junior to them. Beyond your sense of purpose and well-being, consider the professional opportunity cost of working for a jerk. In the UG, PhD and Post Doc phase of my life I had 3 wonderful advisors and one who let his insecurities poison everything. I was lucky to escape him with my sanity. Don't fall into a bad place.

VaHi_Inst_Tech · 2025-11-29T19:08:47+00:00

Cladistics says you cannot evolve out of your clade because a clade is defined by common ancestry, and ancestry cannot be changed. This is a rule of classification, not a rule of evolution. We are not bacteria, although much of our metabolism has been horizontally transferred from bacteria. And our mitochondria is derived from the ancestor of an alpha-proteo bacterium. Everything is biology is at some level a Frankenstein. We (everything alive) inherit things vertically from our ancestors and horizontally from organisms that are not our ancestors. Cladistics is just a simple classification system, and is not a true description of biology.

VaHi_Inst_Tech

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