Molecules assemble in water, hint at origins of life

Feb 20, 2013
Molecules assemble in water, hint at origins of life
Professor Nicholas Hud, Georgia Institute of Technology, has been trying for years to find simple molecules that will assemble in water and be capable of forming RNA or its ancestor. Credit: Georgia Institute of Technology

(Phys.org)—The base pairs that hold together two pieces of RNA, the older cousin of DNA, are some of the most important molecular interactions in living cells. Many scientists believe that these base pairs were part of life from the very beginning and that RNA was one of the first polymers of life. But there is a problem. The RNA bases don't form base pairs in water unless they are connected to a polymer backbone, a trait that has baffled origin-of-life scientists for decades. If the bases don't pair before they are part of polymers, how would the bases have been selected out from the many molecules in the "prebiotic soup" so that RNA polymers could be formed?

Researchers at the Georgia Institute of Technology are exploring an alternate theory for the origin of RNA: they think the RNA bases may have evolved from a pair of molecules distinct from the bases we have today. This theory looks increasingly attractive, as the Georgia Tech group was able to achieve efficient, highly ordered self-assembly in water with small molecules that are similar to the bases of RNA. These "proto-RNA bases" spontaneously assemble into gene-length linear stacks, suggesting that the genes of life could have gotten started from these or similar molecules. The research is published online in the .

The discovery was made by a team of scientists led by Georgia Tech Professor Nicholas Hud, who has been trying for years to find simple molecules that will assemble in water and be capable of forming RNA or its ancestor. Hud's group knew that they were on to something when they added a small chemical tail to a proto-RNA base and saw it spontaneously form linear assemblies with another proto-RNA base. In some cases, the results produced 18,000 nicely ordered, stacked in one long structure.

"Thinking about the origin of RNA reminds me of the paradox of your grandfather's ax," said Hud, a professor in the School of Chemistry and Biochemistry. "If your father changed the handle and you changed the head, is it the same ax? We see RNA the same way. Its chemical structure might have changed over time, but it was in continual use so we can consider it to be the same molecule."

Hud concedes that scientists may never be 100 percent sure what existed four billion years ago when a complex mixture of chemicals started to work together to start life. His next goal is to determine whether the proto-RNA bases can be linked by a backbone to form a that could have functioned as a genetic material.

Georgia Tech partnered with the Institute for Research in Biomedicine in Barcelona, Spain on the project. The proto-'s two-component, self-assembling system consisted of cyanuric acid (CA) and TAPAS, a derivative of triaminopyrimidine (TAP).

In addition to addressing the origin-of-life questions, Hud suggests the self-assembly process could be used in the future to create new materials, such as nanowires.

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QuixoteJ
2 / 5 (2) Feb 20, 2013
They should mention chirality in this piece, but I don't think they do (had to skim the article due to reading preferences)
ValeriaT
2.8 / 5 (4) Feb 20, 2013
IMO the proto-RNA could form rather spontaneously at the surface of phospholipidic emulsion of aminoacids surrounded with sugar solution. The growing droplets will separate, while replicating and inheriting its surface layer. This lecture could be of particular relevance in this connection.
JVK
1 / 5 (3) Feb 20, 2013
Is the thermoregulation of DNA strand binding of any concern here? The H-bonds do not automagically form, do they? How many years of evolution might it take to get to complementary strands capable of binding? I'm not a physicist or mathematician, which may be why I think this approach doesn't address the origin of life in the context that's required to embrace the complexity of the cell and differentiation of cells in tissues of organs in organ systems of different species that have adaptively evolved to humans via ecological, social, neurogenic, and socio-cognitive niche construction. Is there a model for that -- one that starts with RNA bases that may have evolved from a pair of molecules distinct from the bases we have today? If not, what might be the positive results from this theory?
Whydening Gyre
1 / 5 (3) Feb 20, 2013
They should mention chirality in this piece, but I don't think they do (had to skim the article due to reading preferences)

This is probably the most important part of the process. Without opposing chiralities the chains would not form.
aroc91
5 / 5 (3) Feb 20, 2013
The H-bonds do not automagically form, do they?


Hydrogen bonding is driven by entropy. dsDNA is at a much lower energy state than ssDNA. Base pairing is energetically favorable as it maximized hydrogen bonds and minimizes interactions between the mostly hydrophobic bases and the surrounding water.
Torbjorn_Larsson_OM
5 / 5 (2) Feb 21, 2013
That is nice, but not necessary. Strand formation happens when nucleotides are phosphate activated, say in the alkaline hydrothermal vents that early RNA ribozymes seems selected for. (Works best in hot, anoxic and iron rich environments.)

It is AFAIK true that you need a 5 nucleotide strand to get the ball rolling with base pairing and strand elongation, but those form spontaneously on surfaces, of rocks or membranes as Valeria notes.

In this way RNA replicators crystallize out of a random strand "gas" in ~ 30 000 years, well within the maximum lifetime of today's vents even (100 000 years). Since RNA strand halflife in water is ~ 4 years, these replicator pools can infect neighboring ocean vents and continue evolving before getting autonomous from vents.
Torbjorn_Larsson_OM
5 / 5 (2) Feb 21, 2013
@JVK: Remember that we are predicting the RNA world here, the DNA LUCA came later. Thermodynamics of replicators makes RNA the only known nucleotide that could pre-enzymatically form replicators, and as aroc notes this is thermodynamically favorable.

In fact, there is a phosphate driven force that makes strands crystallize out of monomer "gas" and then replicators out of random strand "gas" in about 30 000 years. (I don't have the ref handy, but google Woo and PLOS Comp Biol.) Crystallization can't stall, even when you have to make replicators or replicators to recover templates. This also breaks chirality into a winning .

If the replicator population crystallizes inside lipid bubbles, they make spontaneous Shoztak cells. Since they promote replicators (strands puts tension on the membrane that thus win during cannibalization for lipids; replicators reproduce strands exponentially), there is a switch from chemical to biological evolution.
Torbjorn_Larsson_OM
5 / 5 (2) Feb 21, 2013
[cont] The pathways from replicators to genes are legion. But as it happens the shortest pathway I know is also the one that fastest liberates RNA cells infecting vents from having hot-cold cycling for replication. (Again, have no access to my refs from here.) The mechanism of protein formation is just used as a molecular ratchet for making cold separation one way, the shortest ratchet is precisely a 3 mer code for an amino acid.

Random sequence is also what protein fold phylogenies sees in oldest folds. But there is selection pressure on appearance of functionality, such as increasing fitness by recycling the protein gunk that cells now becomes stuffed with during replication. Hence enzymes, membrane pores, et cetera.

DNA is, I take it, not an initially heat resistant genetic material as much as a chemically resistant (much longer halflife in water than RNA). When it and its more efficient long strands evolved, it seems to have extinguished RNA life outside of viruses.
JVK
1.8 / 5 (4) Feb 21, 2013
JVK
The H-bonds do not automagically form, do they?


AROC91
Hydrogen bonding is driven by entropy. dsDNA is at a much lower energy state than ssDNA.


Aren't you saying that the thermoregulation of DNA strand binding is of primary concern?

AROC91
Base pairing is energetically favorable as it maximized hydrogen bonds and minimizes interactions between the mostly hydrophobic bases and the surrounding water.


Great! How much of a thermoregulatory change might be caused by a single base pair change? I ask because a recent report linked a change to organism-level thermoregulation via controlled microbial diversity and immune system effects on protein synthesis manifested in receptor-mediated physical traits that enable nutrient-fueled pheromone-dependent sexual selection in invertebrates and vertebrates. In my model, that links the change to nutrient-dependent pheromone-controlled adaptive evolution, which now seems supported by an approach from physics. Doesn't it?
JVK
2 / 5 (3) Feb 21, 2013
@Torbjorn: I'm attempting to address the switch from chemical to biological evolution.What you say is helpful, but beyond my depth. I understand a little about thermoregulation of biological processes (e.g. protein synthesis), so perhaps we can link de novo protein synthesis to thermoregulation of the cellular chemical processes required for adaptive evolution.

DNA is, I take it, not an initially heat resistant genetic material as much as a chemically resistant (much longer halflife in water than RNA). When it and its more efficient long strands evolved, it seems to have extinguished RNA life outside of viruses.


Here you have long strands evolving (? from a 5 nucleotide strand ?) that again appears to place the thermodynamics of H-bond formation at the forefront of adaptive evolution (e.g., from chemical to biological. Doesn't it?

Are you familiar with microRNA, which appears to control intranuclear interactions and nutrient-dependent protein synthesis in the cell?

aroc91
5 / 5 (1) Feb 21, 2013
Not sure what you're implying. Thermoregulation is the maintenance of the body's temperature to either prevent freezing and stalling of cellular processes or denaturing of DNA and proteins at high temperatures.

What do the intermolecular interactions of DNA have to do with total body thermoregulation? I feel like you're making a huge leap in logic here.

JVK
1 / 5 (2) Feb 21, 2013
What do the intermolecular interactions of DNA have to do with total body thermoregulation? I feel like you're making a huge leap in logic here.


I thought you were conversant on this topic; it's not my area of expertise.

Is this illogical? The vibrational force of random molecular motion is manifested as heat, which may pull two strands of DNA apart. At physiological temperature ranges, two DNA single strands align with each other. As two complementary strands get longer, the additive nature of hydrogen bond (H-bond) energies allows their total number to surpass the temperature dependent vibrational forces. H-bonds form between the correct (i.e., A:T and G:C) base pairs.

Nutrients are fuel for the thermoregulation of protein synthesis in microbes and in every cell of every tissue in every organism. For example, glucose uptake is essential. Isn't it?

I feel you are stuck with random mutations theory and can't be logical. Please show I'm wrong about you for extra credit.
aroc91
5 / 5 (3) Feb 21, 2013
The vibrational force of random molecular motion is manifested as heat, which may pull two strands of DNA apart. At physiological temperature ranges, two DNA single strands align with each other. As two complementary strands get longer, the additive nature of hydrogen bond (H-bond) energies allows their total number to surpass the temperature dependent vibrational forces. H-bonds form between the correct (i.e., A:T and G:C) base pairs.


Correct.

For example, glucose uptake is essential. Isn't it?


Depends on the organism. A lot of bacteria can use alternate carbon sources.

I feel you are stuck with random mutations theory and can't be logical.


I feel you're stuck with it because that's all you seem to talk about. If you think you can change the minds of all of academia when there are people that study the effects of mutations and how they contribute to variance for a living, more power to you.

I'm not going to let you derail this conversation.
JVK
1 / 5 (2) Feb 21, 2013
I wrote
The vibrational force of random molecular motion is manifested as heat, which may pull two strands of DNA apart. At physiological temperature ranges, two DNA single strands align with each other. As two complementary strands get longer, the additive nature of hydrogen bond (H-bond) energies allows their total number to surpass the temperature dependent vibrational forces. H-bonds form between the correct (i.e., A:T and G:C) base pairs.


You wrote: Correct.

You previously wrote: " I feel like you're making a huge leap in logic here." Now you say I'm correct, which indicates you are not very logical and probably are not conversant on this topic.

You
I'm not going to let you derail this conversation.


Me: You continue to indicate you are not very logical and that you probably are not conversant on this topic. What caused you to challenge my logic, and then run and hide, schoolboy?
JVK
1 / 5 (2) Feb 21, 2013
For example, glucose uptake is essential. Isn't it?


You wrote: Depends on the organism. A lot of bacteria can use alternate carbon sources.

Me: I thought that the "deoxy" part of each name signified that
each DNA constituent contained a 2'-deoxyribose sugar, and that d-glucose is synonymous with "sugar" in common usage.

Which organisms use alternative carbon sources as nutrients that exclude their need for sugar? I've always thought that glucose uptake was an essential aspect of adaptive evolution. But, as I indicated, I'm not informed about the physics. Others also may not have achieved your level of understanding. Please tell us more about the bacteria that don't use glucose (e.g., in their DNA), or that don't need it to survive. I've heard about anaerobes that survive on iron. Are you saying there are lots of them, or lots of bacterial species that don't require glucose uptake?

aroc91
5 / 5 (1) Feb 21, 2013
Now you say I'm correct, which indicates you are not very logical and probably are not conversant on this topic.


Non sequitur. Your deduction was correct and I confirmed that.

Which organisms use alternative carbon sources as nutrients that exclude their need for sugar?


Where did I say it excludes their need for sugar? You don't have to have glucose in a media to get bacteria to grow. They can take up other carbon-containing compounds and undergo gluconeogenesis. Lactose or even non-sugar carbon compounds can be used. Proprionate, acetate, etc. They get turned into the necessary sugars eventually.

http://www.ncbi.n...1287611/

You're asking questions and I'm answering them to the best of my ability. I'm not going to hold a grudge and be a dick to you whenever I get the chance. I'd appreciate it if you acted like an adult.

JVK
1 / 5 (2) Feb 21, 2013
Your deduction was correct and I confirmed that.

After claiming that I was not logical.
You're asking questions and I'm answering them to the best of my ability.

After claiming that I was not logical, then stating I was correct.
I'm not going to hold a grudge and be a dick to you whenever I get the chance.

Then why did you claim I was not logical, then state I was correct, then drag me into debate about glucose uptake?

Do you know how difficult you make it for others to follow a logical argument for nutrient-dependent pheromone-controlled adaptive evolution? If you can't grasp the logic, ask a question.

Instead you simply state I'm not being logical, when I am. Meanwhile, discussion is side-tracked on this issue via precisely the same nonsense you have introduced into other discussions.

I'd appreciate it if you acted like an adult.


I'd appreciate it if you would inform yourself about biologically based cause and effect.

JVK
1 / 5 (2) Feb 21, 2013
For intelligent discussion on physics and biology see: http://www.the-sc...eration/
For intelligent discussion on adaptive evolution see:
http://www.nature...20130221
aroc91
not rated yet Feb 21, 2013
I never said you were being illogical, per se. I don't want to patronize you and ask if you know what the term "leap in logic" means, but it doesn't mean "illogical". I'm just saying that there's a lot of middle ground between entropy on the atomic scale and full-body thermoregulation and your wording implied a direct link between them.
JVK
1 / 5 (2) Feb 21, 2013
The DIRECT link between them is an alanine substitution for valine that links the thermodynamics of internuclear interactions and protein biosynthesis in cells to whole organism thermoregulation in mammals via what we know about invertebrates. The link to mammals includes a human population with characteristics that enable sexual selection for the underlying molecular mechanisms at the level of logic I "leaped" from.

The link doesn't get more direct than that in my model of nutrient-dependent pheromone-controlled adaptive evolution. (If I said the nutrients were amino acid substitutions, could you make the connection in the context of glucose uptake et al?)

So, now we either link the physics to the real RNA world, or invent a world that's consistent with a ridiculous theory of random mutations. I think I know which world you prefer, but your world makes no sense given the common molecular mechanisms of PHYSICS and BIOLOGY. Does it? That's why I make the leap in logic. You can't!
aroc91
not rated yet Feb 21, 2013
What does that have to do with the entropy of individual DNA strands?
JVK
1 / 5 (2) Feb 22, 2013
What does that have to do with the entropy of individual DNA strands?


Do you understand anything at all about protein biosynthesis?

"...phosphorylation promoted CAD oligomerization and thereby stimulated de novo synthesis of pyrimidines and progression through S phase of the cell cycle in mammalian cells. Thus, mTORC1 also stimulates the synthesis of nucleotides to control cell proliferation." http://www.scienc....1228771

If not, please leave the discussion open for those who might be helpful to others who are interested in linking the common molecular mechanisms of PHYSICS and BIOLOGY. I'm trying to learn something here, and you're asking broad-based questions after first indicating you might know something about the topic. Not exactly a TROLL, but just as annoying.
aroc91
not rated yet Feb 22, 2013
That paper has absolutely nothing to do with DNA strand entropy.
JVK
3 / 5 (2) Feb 22, 2013
That paper has absolutely nothing to do with DNA strand entropy.


Previously you wrote:
Hydrogen bonding is driven by entropy. dsDNA is at a much lower energy state than ssDNA. Base pairing is energetically favorable as it maximized hydrogen bonds and minimizes interactions between the mostly hydrophobic bases and the surrounding water.


Are you now saying that "...phosphorylation promoted CAD oligomerization and thereby stimulated de novo synthesis of pyrimidines and progression through S phase of the cell cycle in mammalian cells" also automagically occurs and has nothing to do with DNA strand entropy?

I get the impression that you would like de novo synthesis to occur automagically so that it could be attributed to a random mutation, but that you don't know enough about cause and effect to know what you don't know, and are forced to rely on theory, which is a poor substitute for facts when attempting to link physics and biology.
aroc91
5 / 5 (1) Feb 22, 2013
Can you explain your point like a regular human being for once? All you ever do is make vague connections between, at best, distantly related topics and then act bewildered when asked to elucidate.
JVK
1 / 5 (2) Feb 22, 2013
All you ever do is make vague connections between, at best, distantly related topics and then act bewildered when asked to elucidate.


No. What I do is publish papers and present findings like other researchers do. You are aware of this. You don't read my published works or look at the posters or presentations, including those that have won awards in neuroscience and in social science.

You're asking me to elucidate here what I have thoroughly detailed at a time when I am attempting to link what little I know about physics to a well-detailed model of nutrient-dependent pheromone-controlled adaptive evolution, which is exemplified in every species on the planet. The model suggests a likely link from physics, and I am indicating the most likely link -- demonstrated in recent works that extend my model to a human population -- is the link from the thermodynamics of intracellular interactions to thermoregulation at the organism level.

Your presence here is what's bewildering.
aroc91
5 / 5 (2) Feb 22, 2013
I am indicating the most likely link is the link from the thermodynamics of intracellular interactions to thermoregulation at the organism level.


So what's the link?

What does DNA strand entropy, the tendency for DNA to form double stranded complexes rather than unfavorable single strands, have to do with mTORC1-induced nucleotide synthesis, specifically?

What. Is. The. Mechanism?

If you were right, nobody would need to go to school. Conferences and Q&A's about published works wouldn't need to be held. You're under some ridiculous assumption that everyone can know everything just by reading articles. That's not how education works. People need clarification. I can read textbooks all day long, but if professors weren't around to explain things, it wouldn't be worth jack shit.
JVK
1 / 5 (1) Feb 22, 2013
If you were right, nobody would need to go to school.

I am right, and that makes you partially correct. Others have said it best: "Successful development ...will result only with the breakdown of existing intellectual barriers ... across the natural sciences, mathematics, computer science, and engineering... The progress of change across the field will also require reformulation of educational goals, including development of ways of teaching biology that are as revolutionary as those that occurred in the 1950s."
http://www.pnas.o...abstract
You're retarding progress with the connection between physics and biology because you're not being taught what you need, and probably won't be for another decade. I'm not going to waste my time on you here, because you aren't even willing to read my published works. You have already failed my class due to not reading the assigned texts. Good luck with the outdated textbooks.
aroc91
5 / 5 (2) Feb 22, 2013
Keep on deflecting.

I'm not going to waste my time on you here, because you aren't even willing to read my published works.


Wrong. I read them and they didn't answer my questions. They definitely don't address what's being discussed here.
JVK
1 / 5 (1) Feb 22, 2013
I'm not going to waste my time on you here, because you aren't even willing to read my published works.


Wrong. I read them and they didn't answer my questions. They definitely don't address what's being discussed here.

Is it clear to you from reading my works that adaptive evolution is nutrient-dependent and pheromone-controlled? Please address the questions the work does not answer if you still think that random mutations cause adaptive evolution.

Once non-random biological cause and effect is established -- as I have done -- we can proceed to any questions you have on the physics to biology link to the thermodynamics of protein synthesis and organism-level thermoregulation associated with a single base pair change that results in an amino acid substitution. If, for example, the change results in a difference in thermoregulation of mitochondrial-nuclear interactions, the physics and biology departments may need to merge their curricula and address defied entropy.

aroc91
5 / 5 (1) Feb 22, 2013
I said I'm not going to let you derail this.

By what mechanism is DNA entropy linked to temperature control?
JVK
1 / 5 (2) Feb 22, 2013
I said I'm not going to let you derail this.

By what mechanism is DNA entropy linked to temperature control?


If you want advanced status in my class, you will first tell others what you have learned so far, schoolboy. Consider it to be like an intelligence test. You appear to have not yet learned that adaptive evolution is nutrient-dependent and pheromone-controlled, which means it is not a function of random mutations/variants/adaptive mutations or whatever terms theorists use to make it appear uncontrolled. But adaptive evolution is controlled by a direct link from sensory input to ecological, social, neurogenic, and socio-cognitive niche construction.

If you're not willing to admit that, you're not intelligent enough to grasp the aspects of physics that must also be linked to the biology of gene x environment-driven cause and effect. No matter what I say, you'll attribute cause to randomness, as is required according to your belief in NOTHING.
aroc91
5 / 5 (2) Feb 22, 2013
Still deflecting due to my disagreeing with you regarding an unrelated topic.

By what mechanism is DNA entropy linked to temperature control?

you're not intelligent enough to grasp the aspects of physics that must also be linked to the biology of gene x environment-driven cause and effect.


You mean the physics that I explained to YOU at your request at the beginning of this? A medical researcher that didn't have the slightest idea about DNA stability, a basic physical property explained by entry level intermolecular interactions, until I informed him? Has hell frozen over?
JVK
1 / 5 (2) Feb 22, 2013
You mean the physics that I explained to YOU at your request at the beginning of this?


For contrast Torbjorn wrote:
Strand formation happens when nucleotides are phosphate activated, say in the alkaline hydrothermal vents that early RNA ribozymes seems selected for. (Works best in hot, anoxic and iron rich environments.) It is AFAIK true that you need a 5 nucleotide strand to get the ball rolling with base pairing and strand elongation, but those form spontaneously on surfaces, of rocks or membranes as Valeria notes.

If you must start with a 5 nucleotide strand, which "(Works best in hot, anoxic and iron rich environments.)" -- How do you get to de novo protein biosynthesis, dsDNA and adaptive evolution of organisms capable of their own temperature regulation at 37 degrees Celsius in the desert or arctic with selection for physical features associated with one SNP (and an alanine for valine substitution manifested in population genetics)?

aroc91
not rated yet Feb 22, 2013
If you must start with a 5 nucleotide strand, which "(Works best in hot, anoxic and iron rich environments.)" -- How do you get to de novo protein biosynthesis, dsDNA and adaptive evolution of organisms capable of their own temperature regulation at 37 degrees Celsius in the desert or arctic with selection for physical features associated with one SNP (and an alanine for valine substitution manifested in population genetics)?



That's a good question and it's being worked on. There's been a lot of progress with general RNA polymerase ribozymes as discrete self-replicating units recently as well as the prebiotic chemistry involved with that. Abiogenesis still has a lot of gaps to fill.
JVK
1 / 5 (2) Feb 23, 2013
That's a good question and it's being worked on. There's been a lot of progress with general RNA polymerase ribozymes as discrete self-replicating units recently as well as the prebiotic chemistry involved with that. Abiogenesis still has a lot of gaps to fill.


Is the question of abiogenesis to protein biosynthesis being examined from a theoretical "god of the gaps" perspective or in the context of biological facts? Again, I'm not informed about physics. But evolution of reversed Tsallis entropy during rat brain development appears to represent the concurrent level of structural and functional hormone-dependent organization (not disordered development). Are high levels of entropy that correspond to more versatility of trinucleotide expression and lower levels that correspond to higher organization of the entire system ignored in physics? Isn't that un-LAW-ful? Or is breaking the law okay so long as the claim is repeated that it's all random anyway?
JVK
1 / 5 (2) Feb 23, 2013
Is the question of abiogenesis to protein biosynthesis being examined from a theoretical "god of the gaps" perspective or in the context of biological facts? Again, I'm not informed about physics. But evolution of reversed Tsallis entropy during rat brain development appears to represent the concurrent level of structural and functional hormone-dependent organization (not disordered development).

Does anyone know how an alanine substitution for valine exemplifies (or not) defiance of the 2nd Law of Thermodynamics. The info on open and closed systems is confusing, because I've seen no examples of a closed system similar to one that involves the thermodynamics of mitochondrial-nuclear interactions where a receptor must arise de novo to enable de novo protein synthesis required for adaptive evolution. It seems to me as if a closed system (the cell itself) opens and closes again to acquire nutrients that fuel the intracellular interactions and stochastic gene expression.

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