Jack Szostak (Harvard/HHMI) Part 3: Non-enzymatic Copying of Nucleic Acid Templates
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Szostak begins his lecture with examples of the extreme environments in which life exists on Earth. He postulates that given the large number of Earth-like planets orbiting Sun-like stars, and the ability of microbial life to exist in a wide range of environments, it is probable that an environment that could support life exists somewhere in our galaxy. However, whether or not life does exist elsewhere, depends on the answer to the question of how difficult it is for life to arise from the chemistry of the early planets. Szostak proceeds to demonstrate that by starting with simple molecules and conditions found on the early earth, it may in fact be possible to generate a primitive, self-replicating protocell.
In Part 2, Szostak focuses on work from his lab studying the membrane components of a simple protocell and in Part 3 of his lecture, he describes experiments to investigate nucleic acid replication by chemical rather than enzymatic mechanisms.
One of the best 3-part lectures I have ever seen.
I love watching different presentations of hypothesis on the origin of life. Thanks for this Dr. Jack Szostak.
Thanks for this series. Got randomly interested in how the first cells came to be and these lectures were fascinating to watch!
Truly stunning work here. To think we have only been at this game for a few decades, only discovering the RNA has enzymatic properties just in the 80's, to see how much progress has been made on such an incredibly difficult topic. We are pushing back the bounds of what we know is possible in the chemical world. Still huge areas to overcome. We're maybe 15-20% there. But also miles from the "impossible" claims of the creationists that life cannot start from non-life.
Not stunning anymore. This research was flawed and has been retracted.
retractionwatch.com/2017/12/05/definitely-embarrassing-nobel-laureate-retracts-non-reproducible-paper-nature-journal/
Jack Szostak concludes, throughout his long lecture, that specific roadblocks exist, to any plausible explanation of how to demonstrate a pathway -- even despite the production of undesirable by-products at many steps, which will permit a solid demonstration of a pathway to create RNA, and eventually DNA, AND, these roadblocks are extraordinary and therefore unlikely to resolve; therefore, let us look at what the Creator of the Universe tells us:
"Then God said, "Let US make man in Our image, according to Our likeness; and let them rule over...all the earth,...
God created created man in His own image, in the image of God He created him; male and female He created them."
(Genesis 1:26-27) "Consider the work of God, who is able to straighten what He has bent? In the day of prosperity be happy, but in the day of adversity consider -- that God has made the one as well as the other so that man will not discover anything that will be after him." (Ecclesiastes 7:13-14) "And I saw every work of God, I concluded: man cannot discover the work which has been done under the sun. Even though man should seek laboriously, he will not discover; and though the wise man should say, 'I know,' he cannot discover." (Ecclesiastes 8:17) Please tweet your response to me on Twitter: ThomasLStanley3.
@@ThomasLStanley That's religious nonsense and has no validity in science
TornadoCAN99, with respect, we are nowhere near 15% to 20% there. All we have at the moment are unproven theories and guesses regarding tiny slivers of the overall problem. One of the many, many questions to answer is what natural force made DNA larger, going from a few hundred base pairs in early, primitive bacteria, to 3 billion base pairs in humans? We should keep looking and experimenting, but we may never find the answers.
JCAH1 does DNA grow larger each time it replicates or is there a big gap between? I.e not enough replications to explain the amount of pairs? I’m just a curious lay observer...:)
This work is nothing less than genius
Not genius anymore. This research was flawed and has been retracted.
retractionwatch.com/2017/12/05/definitely-embarrassing-nobel-laureate-retracts-non-reproducible-paper-nature-journal/
@@kristenmichelle8303 Still genius. Did u even read your link? Of course you did, u little paramecium, but did not have the mental capacity to understand it..
@@ketanovas
did you read the link tho?
@@deathbyseatoast8854 Thoroughly
@@ketanovas
dude his research was literally retracted because of his bias. not very genius like.
His specific hypothesis of abiogenesis is just one of many and it didn't even put up to scrutinization. don't put all of your faith into 1 of these hypotheses because they're just mere speculation with bits and pieces of truth and evidence sprinkled within. still a very interesting hypothesis regardless of its validity. and i'm sure its still a step in the right direction.
i'm sure you and i can agree that we cannot wait to see what other fields bring into the study of lifes origins.
So cool to see that talented people are actually doing the hard work with imaginative ideas. 🙂
Eight years on, where are we now on this fascinating project?
Exciting, beutiful ideas, and promissing work
Thank you for posting this fascinating lecture series. It is amazing how far science has come addressing the origin of life since Urey-Miller in 1952. I can't wait to learn what advances have been made in the 11 years since this lecture!
Very enjoyable and enlightening lectures. I also think it's great how he gives a lot of credit to his grad students. Thank you!
In retrospect, we were totally blinded by our belief [in our findings]…we were not as careful or rigorous as we should have been (and as Tivoli was) in interpreting these experiments.
retractionwatch.com/2017/12/05/definitely-embarrassing-nobel-laureate-retracts-non-reproducible-paper-nature-journal/
Want updated lecture ..after watching this 3 golds
Thank you Dr. Szostak, very compelling ideas and work.
full of information. I definitely, learned a lot! thanks Dr. Szostak! I can study at home during this pandemic.
Dr. Jack Szostak, your research is fascinating. Please keep the videos coming, I keep posting them on facebook, and referring friends to them. Oliver Jamison
The errors were “definitely embarrassing,” Szostak told us:
In retrospect, we were totally blinded by our belief [in our findings]…we were not as careful or rigorous as we should have been (and as Tivoli was) in interpreting these experiments.
Szostak added:
The only saving grace is that we are the ones who discovered and corrected our own errors, and figured out what was going on.
retractionwatch.com/2017/12/05/definitely-embarrassing-nobel-laureate-retracts-non-reproducible-paper-nature-journal/
Please, please keep posting some more videos!!!!!
16:12 : The point he makes here is really interesting. Fidelity and rate of reproduction are intimately linked. Thus, fidelity acquires a selective advantage so early on that natural selection kicks in way before anything like a real metabolism has emerged.
I have my own TH-cam channel which is dedicated to this very topic. SADLY, I have not included any of Dr. Szostak's videos on my channel until now. However, I did mention in my first video that he was my inspiration, so I think that counts.
Very interesting stuff, thanks for posting it.
ABSOLUTELY GENIUS WORK!
Love this. It's dry and full of molecules, and driven by the mechanistic outlook of traditional chemistry. But it's the solution of an intellectual quest that goes back to the ancient Greeks. How, indeed, does a living thing emerge from mud?
The LNA described at 25:20 on could be an initial solution even with the problem mentioned at 27:50. With just G and C in the chain, plus maybe occassional different nucleotides, replication could start at a fast rate - and it would not be important that nothing functional is coded. What is important is that there could be zillions of self-replicating strands: proto-life. Mutations will eventually get something functional without losing the ability to replicate, thus starting natural selection.
Thanks for sharing these thoughts and investigations, doctor Szostak.
(On Monday of April 10, 2023). On the Matter of PhD Jack Szostak (Harvard University/Howard Hughs Medical Investigator) on the the Topic of Proto-cellular Biology of Non-Enzymatic Coping of Nucleic Acid Templates: 1) A Primitive, Self-Replicating Protocell is likely an inherent Chemical Process within the Chance and Environmentally Ordained Consequence, since matter of GMO Cultural Aspects or Multiple, Endless Distractions, but Reactions of Chemistry and Pure Science Hypothesis are demonstrative of Universality of Biological Activity within the Structure and Functionality (Energy within Matter itself). In short, I concur. 2) Now, Nucleic Acid Replication by chemical Mechanism is likely a Proto-Enzymatic impulse itself. Then, as More Stability and Dynamics develops within the Permissivity of the Milieu (Environment Dependent) with Temperature and Pressures, more thorough an Elaborate Polymerizations are Possible with the Presupposition of Heredity as a Monopolization of the Permissive Chemicals to Further Continue the Entropy Antagonism. This could very well be the Overall Mechanism of Matter Self-Assembly and Replication throughout the Universe with Parameters of Energy Transduction, Heredity Encoding and Self Assemblage Highly and Intrinsically Tied to the Relevant Factors of Temperature, Pressures (Atmospheric Pressures if any) and Availability of Matter (Protons or Hadron/Lepton Self Assemblage at Black Holes is Speculatively Impossible). Therefore, Habitable Zones of Carbon-Based Biology is likely to be inconsistent at this Milieu (Protein Degeneration, Nucleic Instability is rather Earth Specific), but certainly Quanta and more so Hadron-Lepton Subatomization is Self-Assemblable with Energy Permeating the Universe in Fashions and Forms yet Undisclosed by Conventional Ideations of Subatomic Antimatter Hypothesis. PhD Jack Szostak, es geht sehr gut zu vermehren die Erkenntniss der Lebens aber die Andere Wissenschaft schwarz und sehr Dunkel Koennte Sein. Heil!
Inspiring !
What if there was a precursor the RNA world that we just are not aware of. The level of complexity of the reactions he discusses here appear to me to be too great to have occurred in the primordial soup. I think there was some chemistry that is not RNA based which preceded it. Watching his excellent lecture makes me think about the structure and chemistry of DNA. If somehow living organisms evolved in the primordial soup beyond DNA to a chemistry that is radically different would we be able to determine that yes DNA was a molecule that had been used as the genetic foundation of a living organism?
Keep on going bro
Thank you, very useful.
Does anyone know the geochemical pathways the create fatty acids. I can't find this info anywhere even though it's so important to many of the hypotheses in the theory of abiogenesis.
Check out the work for D. Deamer. He showed that fatty acid vesicles could be formed from carbon-containing meteorites
This very series you are watching discusses one approach. Go back and watch it again, you've both missed it!
Avidly watched all 3 of these excellent lectures.. some related questions... I)are the RNA analogues you developed homochiral in the templates polymerization reactions II) related to this, you did not cover much on the homochirality of bio molecules... on this is would be really pleased to hear you view on how the desymmetrization would take place...
E.g. recemic pre-RNA templating systems, then some accidental process whereby the successful mother strand from which we are all descended ended up with a homochiral strand set which selected out more and more D-sugar enantiomer... a bit analogous to the 2’ 3’ variation you saw resulting in lower Tm (hence more successful copying)..
Or some other external templating which generated a pool of significantly chirally enriched building blocks..
...what is probably certain, by observation, is that life of substantial sophistication required homochirality.... that is, it’s unlikely that a Darwinian process would end up with this if there were a more statistically easy solution...
I suppose, the next question is what sort of probability can we assign to the desymmetrization process... or putting it another way ...are we alone ?
Best Alan
This research was flawed and has been retracted.
*”Definitely embarrassing:” Nobel Laureate retracts non-reproducible paper in Nature journal*
*"In retrospect, we were totally blinded by our belief [in our findings]…we were not as careful or rigorous as we should have been (and as Tivoli was) in interpreting these experiments."*
I have to say though, that Jack Szostak is a very honest scientist. He admitted his mistake and retracted the paper himself.
retractionwatch.com/2017/12/05/definitely-embarrassing-nobel-laureate-retracts-non-reproducible-paper-nature-journal/
@@kristenmichelle8303 So, have you looked into any alternative hypothesis?
I see how these people have created a cell.
Very cool.
:) love this guy
Great work. It is trying to understand the chemical pathways or material pathways. This is only half the work, the other half being sequential information or perhaps the math as opposed to the chemistry. Sequential information is non-material or non-dimensional.
Early reproduction is reproduction of information as well as chemistry. without sequential information everything is dead in the water as far as abiogenisis.
Electricity created all life. chemistry had the binding property to resist a heat induced change. voltage was needed to drive the selection process of the enzymatic comlex molecules. electricity was also needed to split molecular bonds to separate the newly bonded catalyst from the genetic sequence. without electricty there would be no life.
You now that all chemical processes are done my interactions between charged particles,right?Chemistry wouldn'
t be possible without eletricity
You sound like an expert. what research papers have you been cited in?
He is a Nobel Prize
i hope that soon you will explain how motor-proteins and DNA repair 'self-assembled'
self assembly is the easy part (they do this all the time. Follows two basic rules of hydrophilic and hydrophobic parts orienting themselves either towards or away from water). What takes time is getting the right sequence
They didn't "self-assemble", they derived from simpler components that did other things. For example the core function of motor proteins isn't to move organelles etc, but instead to hydrloyze ATP. There are multiple ATPase superfamilies that link an output (products) to a basic chemical reaction via a particular domain. All of which are selectable after diverging from the ancestral function via mutation, including gene duplication.
Let me add, pathogenic viruses and bacteria interact and utilize motor proteins in very specific "irreducibly complex" ways .If you are implying intelligent design in your initial comment then the extension of that comment is that these were designed to cause disease.
Do yo think it is reasonable to surmise that because it is so difficult to understand how life got going it would suggest that life is not so common in the universe.. ?
Honestly, not at all. Keep in mind that the amount of "experiments" that can happen on any suitable planet over billions of years _vastly_ outstrips anything researchers can do here and now. We're intelligent, so we can steer our experiments towards avenues that seem hopeful - nature only had blind tries. But nature also has a lot more time and a lot more space.
In fact, one thing these experiments do is give us an idea of how simple the most simplest replicators could be. And that makes a huge difference to the expected rarity of life in the universe - since the chance of having a suitable replicator drops exponentially with the complexity of a minimal replicator. The difference between a galaxy full of life and a galaxy with just a couple hundred planets with life is just a few more units. Of course, ignoring the possibility that life might spread from planet to planet.
If a protocell forms RNA-like (e.g TNA) polymers enclosed within a replicating vesicle, how does the RNA polymer obtain it’s genetic functionality? Wouldn’t the sequence simply be a random and non-functional sequence of RNA-like nucleotides?
This work described in the video is not yet dealing with where the strands acquire their information content. But, you can see where the work is going. Once you have self replicating nucleotide strands, even if they are not yet coding for any Darwinian "traits", it should be a non-insurmountable task to have certain strand sequences providing a replication advantage over different strands. Perhaps an added stability to the strand is achieved by random chance, or say a higher fidelity of incorporation, thus increasing the effective rate of strand replication. There are many scenarios that could lead to a particular strand sequence having a replication/survival advantage. This would be the beginning of "biology" from the purely chemical process.Fascinating stuff....
TornadoCAN99 Good thoughts. I think he does cover the topic of how RNA could form in Pt.1. I remember he talked about a Montmorillonite clay that acts as a natural catalyst for forming organic molecules.
Yes, RNA formation is covered nicely. However, the question being commenting on above is about the information content within the RNA sequence. In other words, how does the nucleotide sequence go from just random letters to letters coding for something like an amino acid sequence, open reading frame, or even a splice site? The response made above was there can be various scenarios where a non sensical sequence of letters is selected for due to stability or improved replication rate etc. That's how natural selection begins the slow march to adding information content to the RNA chain.
TornadoCAN99 Right. There does not have to be a goal of order or some specific trait for the RNA vesicle to achieve.
Once self-replication is possible the game of survival is on, and really there are only two possible outcomes, survival or extinction. Traits which promote replication and/or longer-term survival will be selected by the laws of the universe. The specific letters of RNA depend only on their ability to promote survival, they only makes sense afterward, as intelligent life evolves and looks at it ("Oh, look, that's the codon that makes the RNA to form a secondary layer around itself").
One could make a valid case that even a random string of nucleotide bases, having no coding content in any conventional sense, still has information content...it's just at a different, less sophisticated level. The chemical structure, bond angles, bond strength, chirality (handedness) etc are all being selected for by ability to self form initially, then to be self replicated as a strand and to hang around long enough to cycle through many rounds of replication and vesical splitting.
So there is no sudden transition to beginning natural selection....its just a progression from chemical selection to something with higher, more complex information content.
Love you from india
If you think, there is no fidelity problem and there is no RNA replication problem. We need better ideas.
a question to Jack,
It is regarding DNA repair - an issue of the logic:
How the cell knew, that the DNA is unstable and there will be DNA copy-errors after each DNA replication / cell division? How the cell knew there will be a lot of errors? Where the DNA repair mechanism came from?
That is an interesting question. Having studied this quite a bit, allow me to try to explain this. Watching his three part series a few times also helps, as he does sort of explain the answer you are looking for.
The cell did not know, of course that it contained DNA that needed copy-error correction. So it wasn't some Lamarkian magic that brought about error correction mechanisms. Rather, DNA replication fidelity is typically low, especially absent some fidelity-increasing feature.
Think of it in terms of natural selection and it becomes more clear. Let us imagine two protocells with some type of RNA analog genetic material inside. Inside one protocell, the RNA is really quite useless. Nothing about the order of molecules making up the RNA sequence does anything to help the cell compared to a cell lacking the RNA altogether. In the second protocell there is also an RNA macromolecule. But this one has an arrangement that does something, perhaps as simple as a reduction of polarity such that the interior walls of the protocell are more stable, making it hard for that macromolecule to leak out and get destroyed. The second protocell has a better chance of surviving longer than the first more-fragile cell. Whatever the random change was that made the RNA in the second cell useful is what also makes that RNA now what we would call information. Instead of a random jumble of things without any purpose or meaning, the random jumble of things has a particular section that does something, giving itself meaning.
The analogy would be like typing random characters. I could type one string of characters which means absolutely nothing. We would say it conveys no information. But in a second string of random characters, by mere chance, I spell out the word "hello." This then is identified as meaningful and therefor that second string contains information.
In genetics, the information only really has meaning if it has some function (or at least used to have some identifiable function). Otherwise it is just noise. What would make the RNA 'genetic' would be a cell-division cycle of some sort. As Szostak had said, this could be something as simple as the sheer forces of the surrounding medium, as they have observed protocell membranes (vessicles) divide on their own if there is a differential. Now, to get genetics, one then needs to have RNA copy, split, and then send one half into one vessicle and the other half remain in the first vessicle. As we know RNA can copy itself now, absent an enzyme, we can now think of a new thing for natural selection to act upon.
In once case we have a protocell that contains replicating RNA. It does a horrid job at it though, such that whatever useful function that RNA performed was lost upon the cell division. The new protocell containing the flawed RNA doesn't survive and gets cannibalized by other protocells. In another RNA protocell we have, by chance, some feature of that protocell that ensures higher fidelity. Upon division, the second protocell survives, having inherited the beneficial sequence of the original RNA strand. This is the first genetic information transferred.
As we know that RNA can fold itself into an enzyme, and that depending on the original RNA sequence, that enzyme could perform replication at higher fidelity, it is just a matter of time before an RNA sequence develops that has that necessary structure to have that end purpose. In such a protocell, it would be more pervasive, surviving much better than the other protocells lacking that useful feature. Natural selection would favor it, and ultimately those types of protocells would dominate, cannibalizing the material of the poorly equipped protocells.
As he posits the RNA came before DNA, we can then extrapolate that the same basic game played out as DNA came along, where an enzyme was created by RNA that acted in a beneficial way, specific towards ensuring fidelity. In the case of DNA, the exact pathway of this chain of events is unsolved (as far as I know).
So the cell obviously didn't know anything. It can't. The nature of replicating molecules is that fidelity is pretty poor. These are just chemical reactions after all. The fact that ANY fidelity exists is a matter of the limitations on how these molecules can form in the first place. The shape of them is also defined by restrictions based on their physical nature. This is called conformal symmetry. Just as lego blocks tend to create blocky structures, RNA tends to create structures contingent upon the shape and types of molecules that constitute it. There is only so many ways an RNA molecule can connect to MORE material. Because of these restrictions, there is SOME fidelity to the replicated strand. Just as a key only fits a particular lock, the restrictions of form dictate the restrictions of interactions.
DNA could not exist very consistently without such an error correction mechanism also being present. But just as in the chicken/egg question, there is only one good answer. In this case the enzyme came about before the DNA molecule came about. Thus, when strands of molecules started forming into DNA type macromolecules, the enzyme was present in some cases to ensure fidelity. Just as in the analogy of our RNA protocell competition, the protocells that contained DNA AND the enzyme survived better and passed on useful genetic information MORE than protocells that LACKED that useful feature. Natural selection kicks in, favoring the better over the weaker, and pushes for even more favorable changes (as well as changes that have no detrimental effect). The code grows more complex, in that more useful information accumulates, because having 4 or 5 beneficial features ensures survivability (which is what defines it as beneficial) more than say 1 or 2 beneficial features. Eventually it is an arms race, where the random codes that contain even more useful bits survive more often than more primitive basic and more random codes, driving complexity up over time.
Keep in mind that we are imbuing this idea of code upon these sequences. The information is only identified as such because it is a string of molecules that has some beneficial feature to the overall structure. If it lacked this, it would not be identifiable above the noise of random letters. We can look back at it NOW as a code because we can identify the useful bits from the noise. But they still came about randomly. They were just favored statistically over those that lacked such handy bits.
by the way, the chicken/egg question is very simple to answer.
A designer created the chicken (not from an Egg)
The designer built in the egg replication mechanism into the chicken, so the 2nd chicken could come from the Egg.
Actually, it is very simple when you use your head and do not listen to some imbeciles, even if well educated imbeciles.
Smart people know, that this is the only reasonable answer, they do not need to ask what was first....
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how do cell's "know" now? They don't have knowledge the way humans know that "oh my arm is broken...better go fix it." Instead the incorrect copying of RNA could cause problems for the protocells and thus it would be naturally selected against and cease to exist/break down. However if a cell evolves a solution to this then it will be naturally selected for and continue to exist. It's not a mater of whether they know there's something wrong; knowledge of it irrelevant. In fact, the unreliability of rna replication may have been essential to the development of rna repairing mechanisms.
You're wasting time with walls of text they won't even read, let alone understand. They'll just move on to other videos and pose the same tired old "rhetorical gotcha questions -HA! Explain that scientists!".
@@aniekanumoren6088 Most importantly, a repair mechanism doesn't need to be particularly sophisticated to be useful. Even today, DNA repair mechanisms don't know what the DNA is "supposed" to look like of course - they just handle things like "oh, there's an oligomer that hangs outside, so the strands don't fit together... cut" or "oh, there's a wrong base in a pair". They know nothing about the "content" of the DNA strand, they just fix broken constraints - much like parity check in a computer memory.
And all of this is just the result of the selection on what's better at copying. That would include making poor copies unviable - because terminating early means faster copying on average, even if you can't repair mismatches. Some sequences might be particularly prone to mismatching, and others particularly reliable. All of this selection would happen long before the sequence had any other practical purpose, like a shape that catalyses certain reactions or whatever.
Truth is , energy, water, and variety of attractions are the laws. Those laws have no forgiveness.
great video, thank for posting. God's best
I think "Darwinian evolution" starts much earlier than after proto cells and starts right back at the first replicating molecules. I think those first replicating molecules will have been in competition to consume the surrounding material and each other and that cell membrane construction will have been an early defense against chemical consumption from other evolving versions of the replicating molecules.
Without that competition, there is no reason for the cells to get to the proto cell stage. Chance doesn't cut it IMO.
All speculation of course.
Competition means intelligence at work, unless the molecules or cells were capable of such endeavor someone else must have done the decisions work for them.
@@obiecanobie919 My speculation doesn't mean chance doesn't happen, it does. But its not chance to make a large jump to a proto cell, its chance to evolve towards a proto cell.
Not really speculation but Darwinian selection only really applies to organisms. Chemists know from non biological chemistry that some reactions out-compete each other,
@@patldennis I dont think so. Survival of the fittest doesn't imply conscious decisions or even learned reactions like you might find in the most basic organisms. In this context it means that a particular replicating molecule was more effective or efficent than its neighbours. And more effective or efficient at evading being destroyed.
@@medhurstt Bacteria don't develop antibiotic resistance via conscious decisions or learned reactions. " Evasion" implies reaction too. I think what you mean is that reactions with faster kinetics simply produce more product (at the end of the day-themselves)
This might be heretical, but it seems to me that the process of natural selection could apply to any self replicating system. The genotype-phenotype cycle is possibly a later elaboration of an original proto-organism which had no dedicated genetic material: its genetic structure being embodied implicitly in its overall form and functioning.
I think you are quite right. When you think about natural selection, it is really just picking up "the chosen ones". You don't actually need complicating DNA (genotype) -> RNA -> protein (fenotype) mechanism. You only need some information that will pass on and some atribute that will help it to do that.
"This might be heretical, but it seems to me that the process of natural selection could apply to any self replicating system."
Absolutely. In fact, interesting results are obtained when setting up technological design processes in a way that natural selection can be applied. One obtains novel solutions that work, but would not necessarily be thought of by a human designer.
Not heretical at all! Very well established and conventional, I would say! Natural selection could (and indeed must) occur in all systems where different individuals have heritable differences in ability to replicate. A lot of what this lecture is about, it seems to me, is identifying the original replicators and what gave them differences in replicating ability.
Paul Coddington but the selection is by humans. the intelligence is in the selection process.
Does anyone know the geochemical pathways the create fatty acids. I can't find this info anywhere even though it's so important to many of the hypotheses in the theory of abiogenesis.
Hi
I have an idea of how a single molecule can self replicate:
. start with a random RNA strand. we will call this - 'S'.
. half of this molecule will behave like a rhibosome. we will call this half - 'R'
. the other half of the RNA molecular strand is 'normal' RNA information. we will call this half - 'I'.
. R 'naturally' folds into a rhibosome shape.
. R starts going over I and creates a separate copying-rhibosome out of this information. we will call this copying-rhibosome - 'C'.
. as soon as C is complete, it starts going over S in its entirety.
. C creates a perfect copy of S. we will call this copy S'.
. C repeats creating copies of S ad infinitum.
. each copy S' starts creating its own copies.
. natural selection kicks in - life follows.
Notes:
. This process needed to have happened only once in the history of earth.
. We did not need a membrane.
. A membrane could follow from natural selection processes or
. A membrane could have followed from the 'protocell membrane' theory.
Why would the RNA naturally form a ribosome?
J Bishop
"Natural" = random
We only need this to occur once.
In the course of million of years over the vast oceans - this is not unlikely.
Assaf Wodeslavsky Well, I agree that under the right conditions the possibility is high enough to have created life at least once!
But if you have a ribosome just hanging out in it's vesicle, it doesn't mean it will initiate a self-replication event. What triggers that?
J Bishop - good question. I'll need to re-think my theory.
Assaf Wodeslavsky no one has designed a working RNA ribosome . also you need transport RNA . moreover an RNA ribosome would undoubtably be larger than existing protein/RNA ribosome. how likely is it that RNA is stable enough for such a large RNA structure, if one exists, could survive long enough to do anything.
Unless we find a ribozyme that catalyzes covalent bond formation between ribonucleotides to create random RNA sequences supports for the RNA world is weak.
There is an abyssal gap between small biomolecules (amino-acids, sugar, lipids, bases or even liposomes) and the simplest prokaryotic cell. In nature, why can’t we find intermediary assemblies of biomolecules to bridge the gap ?
Well, biomolecules assemble in the lab and in puddles of water all the time. As to why even more intermediary steps don't exist, probably because the millions of years needed to reach them are different nowadays compared to early Earth, as in, there are other more modern molecules eating the vesicles up!
Self assembly and self replication of ribozymes has been demonstrated in a number of studies.
Probably a stupid question, but if there once existed protocells, why do they not still exist?
Good question. The problem with teaching that a protocell existed in the distant past, without any trace of it in reality or in the microbial fossil record, is that it makes this science less than empirical, and more like a speculative assumption. In fact, this entire video on the non-enzymatic copying has been debunked. Here is a link telling about this:
retractionwatch.com/2017/12/05/definitely-embarrassing-nobel-laureate-retracts-non-reproducible-paper-nature-journal/
For the same reason once there was a proto-chicken that is not around anymore: things change and in the long run things change a lot. Just think ammonites: they used to be everywhere but they are nowhere anymore, just think australopithecines... The difference is that these larger semi-mineralized organisms left fossils, proto-cells would not becayse they were soft and tiny.
maybe they are eaten instantly by modern bacteria.
@@kristenmichelle8303 Thanks Kristen for highlighting this information
As usual, more questions than answers. Great guy, intelligent discussion, but light years away from any chemistry reproducible in natural conditions that could conceivably generate living systems. Hundreds of other concurrent reactions are necessary to generate information, metabolism, growth, and division. Without such systems in place, any RNA will shortly hydrolyse.
Great work, but it's another example of material processes explaining early life. Bottom line early cellular life would require high amounts of sequential information. Information necessary for design is non-material.
Do u know the geochemical pathways the create fatty acids? I can't find this info anywhere even though it's so important to many of the hypotheses in the theory of abiogenesis.
A big question. DNA/RNA works from the inside out and not outside in. In other words if you lost a limb it in no way affects your DNA. If RNA finds a home in a floating membrane, DNA/RNA doesn't begin to produce membranes. That would take an extreme amount of sequential information. There is no natural selection and mutation has no mathematical ground to stand on.
Have you watched the earlier videos in the series? He tackles this subject. Micelles form spontaneously from a solution of sufficiently dense lipids. These vessels can be home to complex chemistry, including those self replicating molecules. Sufficient density of RNA/DNA puts a outward osmotic pressure from the inside of the cell, which gives it precedence to absorbing micelles with less of that osmotic pressure. Because micelles are being produced in the environment, there's no need for the genetic material to facilitate the production of lipids at this point, however through successive generations and inherit mutations, there may be a mutation that allows the production of phospholipids, which incorporate themselves into the lipid bilayer making up the structure of the micelle and subsequently increase the attraction of other lipids to the membrane, creating an evolutionary advantage in the production of phospholipids. Those micelles which are better at producing phospholipids grow faster, so a selective pressure drive them until they are able to construct their membranes without needing the lipids to be produced in the environment.
You would have been able to answer your own question had you watched the videos in order and you've presupposed that your question is unanswerable before you asked it, so you've poisoned the well and are therefore engaging in fallacious reasoning.
Hey Jack, what a amazing brain you have! I have a new theorie. First i want to introduce myself. My name is Sadé Spoor (32) from the netherlands. What do u think about the idea of what kind of incredable creature the universe is vorming. I guess it can be related of the family of the animal Lazy 0÷)
I am so glad with al this new sience.. wish my theorie could be ever discovered but i dont think so. I can only speculate and dream of it. The real part of why people believe in god. :p
The genetic information stored in RNA is the only thing that makes that molecule important. It is one thing to discuss how RNA is made and how it might replicate, but how did the amino acids in early RNA occur in an order that was biologically useful, rather than "garbage"? This is the point at which some people think that a super being stepped in - to arrange the amino acids in an order that gave primitive life a chance. Once that was done, life took over on its own. A minor point: RNA is not a polymer because the amino acids do not occur in a repeating pattern.
Wut? Who are you?
We should stop telling what nature to do, but we need to ask nature what actually happened. I like Jack, but he is in a wrong way.
We're doing that too. We hope to find a better understanding out of a combination of potential workable solutions, and the historical residue left in modern cells. But we know for certain that a _modern_ cell (even a prokaryote) couldn't ever form spontaneously. The vast majority of the historical record is irrevocably lost. We can't ever find what _actually_ happened - but we can show that _something_ could conceivably work. And that's all the proof you need.