Close-Up View of DNA Replication
ucdavis.edu
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[1]: http://www.nature.com/nature/journal/v518/n7540/abs/nature14...
I suggest God did it requires the most faith and incidentally more likely leads to a stifling of curiosity. God did it might possibly be true but it is the refuge of the incurious. It can be used at every turn. It can be used to answer all 'why?' questions. And thus it is singularly the most incorrect answer in history. That's why God did it requires the most faith. It has been wrong so often that I wonder why it hasn't been discarded for the intellectual crutch that it is.
The process detailed here (https://www.youtube.com/watch?v=OjPcT1uUZiE) no doubt has been refined through evolutionary pressures, but even the earliest of organisms must have had something similar take place in order for the traits encoded into DNA to be passed from generation to generation. This mechanism is something we can barely observe with the most advanced technology available to us, let alone reproduce or synthesize on our own. I think this is what the original question was about, where did that first process come from?
As for how: chance.
Given a bubbling stew of organic compounds with chemical energy gradients available, eventually a random reaction created something with the ability to self-replication.
Almost irrelevant of how simple / ineffective / unreliable that method was, it represented a huge advantage (in the numerical offspring sense) over sheer random reactions. This life therefore dominated and exploited the available energy to reproduce.
Then mutation begat mutation, as selection picked favorable traits and more and more complex systems of encoding and reproducing traits developed.
I'm not saying it's been proven (to my knowledge), but it seems reasonable given what we know. And moreover I don't see any "the beginning must have been fundamentally different than business as usual" requirement for whatever happened. As Ian Malcolm says, "Life finds a way."
I've always heard people just assume it would happen given enough time, but I haven't seen anybody actually calculate the probabilities and deal with the real numbers.
Also, beyond the video, the simplest bacteria we have been able to discover/modify requires around 200 different types of proteins to function (numbering in the 100,000s all together in their specific arrangement inside a cell membrane.)
This is the minimal viable life form we know, yet just to randomly construct a single protein from amino acids would take a practically infinite amount of time given all the resources of the known universe.
Then 100,000s of those proteins have to randomly find themselves inside a cell membrane...
People are quick to dismiss complexity philosophically, but it just avoids the reality of it.
The numbers are so far beyond astronomical they make astronomical numbers look like basic arithmetic.
Anyway, I was hoping you could provide some feedback on whether you think the math is accurate and why it should or should not be considered.
So this would only apply when a specific sequence is required.
In analogy, if making a puzzle the first piece could be cut randomly. However, the following pieces would have to fit with the proceeding pieces. And each additional piece would grow in specification.
So for a cell, it is true that there could potentially be a large number of proteins that could prove useful. However when that one protein requires 99 other protein types that "fit" with it in the puzzle of a single cell, then you have a specific sequence required which would be more and more precise for each additional protein.
In addition, since there is a need for 1,000s of copies of each protein type, there is also a need for factory proteins of even greater complexity.
In the case of every life form on earth, they all have these protein factories built-in which read the rna to create specific proteins.
Although, there might potentially exist other possible protein combinations that could create an alternative functional protein factory, any protein factory would have many interacting parts that each require increased specification as each part is included in the design.
In addition, it would be hard for a protein factory to function without a healthy cell holding all the necessary parts close together.
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Another analogy would be like sodoku.
With a blank board, it Is possible to put any number anywhere.
However, as the game gets closer to completion, it requires a specific answer for each square.
If randomly putting a single digit in each square, the likelihood of getting a correct solution would be:
- 9^27 ~ 6e25 (possible random configurations of 1-9 in each square)
Divided by
- ~ 6e21 Number of correct solutions
So it would be like this for a random single cell:
- Number of possible amino acid combinations for ~100,000 proteins of average length ~50.
Divided by
- Number of protein combinations that would function as a living cell
I think it is useful to consider the difference between "Who made this?" and "How was this made?"
As a coder, when I see a program that achieves something I didn't know was possible, it makes me very interested in how it was accomplished. I say, "Great job, that is awesome. How did you do that? Where is the source code?"
In the same way, I see the complexity of life: the required components and all the intricate processes (Search for ""Inner Life of a Cell" on Youtube, it's really amazing).
I try to comprehend the level of complexity and I quickly realize that even Scientific Notation cannot express it appropriately.
So, when I appreciate the Creator and say, "Well done, that is insanely awesome!" I also say, "How did you do that?" "How was that made?" "How does this work?" "What can I do with it?" "Can I hack it to do something else?"
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As far as complexity of faith, the difference is a matter of simple set theory:
Define 2 Sets:
- All things that are made (the Universe) (U)
- All things that are not made (the Eternal) (E)
You have stated that it requires more faith to believe that there are 2 sets (U,E). However, it could be argued that absolutely denying the possibility of the existence of one set (E) requires a stronger choice of faith.
Also, the 2 sets (U,E) makes sense to me, but I see a contradiction in the single set (U only).
It's simple logic:
If (U only) is the set of all things that are made, then the question begs to be answered: "Where did it come from?"
If (U,E), then the answer is obvious: The set of all things that was made (U), came from the set of things that were never made (E).
I often hear: "Ok, where did E come from then?" Well, by definition E was not made. E is not U.
Also, beyond basic logic, if we consider the theory of the big bang which fits with out measurements of an infinitely accelerating expanding universe: The big bang itself points to a specific point in time where the Universe began (or at least was transformed from a singleton to an accelerating expansion).
So if you limit the choice to only (U), again you are faced with a question, "What prompted the initial bang?"
One possibility is that (U=E). Another words, the universe itself must be eternal.
In that case, we would expect an eternal cycle to be observed (something like the Bang-Bang Theory). However, our best measurements indicate an expanding universe that will never collapse and bang again. There is no support for a Bang-Bang theory which would indicate an eternally cyclic universe.
Everything we can measure indicates the universe had a beginning and that it will continue to accelerate it's expansion infinitely.
So the most logical explanation I see is (U,E): that the universe was created (by something that was not created i.e. The Eternal One - aka God).
And that makes me even more curious: I want to explore all the beauty inside the box because now I have someone to direct my appreciation to say, "Well done! That's amazing!".
If you're wanting to look at this as a set problem, let's take the set U as the Universe of everything that we see evidence for and the Occam's razor understanding of things required to precede U.
Now take G as the set that is God - capable of not only creating U, but loving us each individually through some telephathic means, and creating an everlasting existence for each believer in some sort of eternal afterlife.
Belief in U + G requires much more accommodation than just belief in U.
I agree that specific beliefs about the Eternal=God would require much faith since (E) is by definition outside the box (U), and therefore beyond our reach of scientific experimentation.
There might be avenues where (E) could communicate with members of (U), but that is a different discussion. I would recommend as much evidence as possible should be pursued in verifying any specific claims about (E).
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Going back to your first point, I understand that you are saying that there could exist a set (U+O) = all things that are made and all things that preceded it (Occam's Razor).
So that would make it equivalent to the (U=E) set which I mentioned.
Another words, if something exists in the set of things that are made, it was also made, which was made, recursively.
However, when we consider the Big Bang, then something spontaneously prompted the singleton to transform into an infinite expansion.
From this observation, the only possibilities I see are that either the universe was affected by an external actor (E) or the universe itself is eternal and cyclical and the singleton was a temporary state (Bang-Bang theory).
Logically, I don't see a contradiction in either possibility.
However, I do see an extreme difference in quality:
If (E):
Things in (U) have the possibility of eternal significance and stuff actually matters:
- Love - Relationships - Death - Work - Exploration - Joy - Suffering - Eternal Life is a Possibility
If no (E):
On the other hand, if we are simply existing in a cyclically eternal universe, then absolutely nothing matters. We are simply a dot on an infinite timeline. Our atoms will be scattered across empty dark space in an infinitely expanding universe. All is entropy and darkness. Meaning is an illusion.
If the second is true, we don't act like it and we lock away the people who do.
So the only way that anything matters is if you personally live forever?
If, no matter what I do, every atom I have ever encountered is doomed to be scattered across empty space, then any effort of my part is without long-term effect.
For example after the sun goes supernova and burns out as the universe accelerates its expansion to nothingness. In that picture, we are nothing but a dot on a quickly passing timeline. (In this case, all meaning is an illusion and purely subjective. Objective meaning doesn't exist.)
On the other hand, if what I do does affect eternity, then my actions matter whether I live forever or not.
(Of course, if living forever is an option, that's even better.)
I think we make our own meaning in our every actions - regardless of whether or not those effects last for an eternity... which even with belief in a creator of the universe, there's no reason to believe that physics doesn't rule the universe and that it's not headed for heat death.
One way that I like to think of my permanence in the universe is that there's no reason to believe that every thing we do isn't recorded in time. Sure, our consciousness seems to exist only in the present - but perhaps the existence of our lives isn't totally lost in some form. Perhaps this moment of my typing these thoughts will exist as long as our universe does. Could they be accessed at least in read-only form one day by a future civilization? Maybe.
So that definition of "meaning" would be purely subjective meaning. It's meaning that is self-determined.
In your example, maybe an extra-universal future being might be able to read an echo of our impression on the timeline.
That's dreaming of an idea that might make a hint at a sense of purpose.
But that is what I don't find that fulfilling at all.
What I deeply desire is evidence-based objective meaning, and knowing that you and I and everyone else is truly important and valuable and that the choices we make shape eternal reality.
So that is what I see as the qualititative difference between subjective meaning (meaning purely determined by the subject) and existential meaning (one's existence having an eternal value).
Also, yes the dog would have existential value because it would contribute to the eternal effect. In fact, if there is an Eternal One then love and respect for everything he has designed becomes very important and things made from atoms would carry existential value beyond the physics alone.
As a side note, if there is an Eternal One who cares to be known, then he would have to communicate himself and provide evidence for his existence. (And Yes, I do believe that evidence actually exists and I believe it is very good: it fills my heart with hope and deep meaning as I face the problems of this temporary life.)
Anyway, I appreciate the dialog and I hope it is somehow useful for you.
Thank you for taking the time to think through it with me.
Also, why define the "eternal one" as God. That eternal one may be so simple, and dumb, like that DNA replicating machine.
Usually "God" implies conscience. Are you okay with brainless God? And if you are okay with brainless God, then the word God has become meaningless, because now God can't even think, it surely then isn't God of any religion.
Your logic boils down to the fallacy of special pleading and thus fails. You can't define God into existence by calling him eternal and avoiding the question of where he came from.
> One possibility is that (U=E). Another words, the universe itself must be eternal.
That is the only logical choice.
> In that case, we would expect an eternal cycle to be observed
No we would not, that an eternal cycle might exist does not imply it can be observed or detected.
> However, our best measurements indicate an expanding universe that will never collapse and bang again. There is no support for a Bang-Bang theory which would indicate an eternally cyclic universe.
Untrue, if it expands out to nothingness, nothingness itself is prime to create a big bang as nothing is not a quantum stable state. The real answer is we don't know.
> So the most logical explanation I see is (U,E): that the universe was created (by something that was not created i.e. The Eternal One - aka God).
There's nothing remotely logical about that, you've just invoked special pleading and presumed creation by something is necessary when we in fact know it is not. The universe just is, that's the only logical conclusion we can make from the available evidence. You've dressed up a logical fallacy in set math to perhaps try and make it seem reasonable, but it isn't, it's just bad logic.
- Nothing can exist that wasn't made - Except the universe: it wasn't made
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If one says "the universe just is" one cannot claim logical superiority to the statement "(E) just is".
Beyond that, you can't claim special pleading on my part and still argue it's OK for God to exist without being made, that's special pleading. All special pleading is fallacious. None of my statements are special pleading, I haven't claimed nothing can exist without being made. That's one of your premises, not one from the science argument.
> If one says "the universe just is" one cannot claim logical superiority to the statement "(E) just is".
Yes one can for one simple reason, the universe's existence is not in question, therefore stating that it just is is logically superior to stating that E just is as E, i.e. God, is not known to exist and thus that statement is begging the question.
More simply put, you can't prove God exists with math, math doesn't always map to reality. Existence requires evidence in science, math never serves as proof of physics absent physical evidence, it can only serve as a guide in looking for corroborating evidence.
Ultimately however, the main point I'm making is that your logical analysis is fallacious, it boils down to nothing more than special pleading and the baseless presumption that things require a creator.
i think that all reasonable people believe something has to have existed that wasn't created. It is a bad argument to say we have to have been created because of our complexity.
It appears you choose or have been led to conclude that god exists and it the uncreated thing. I have been led to conclude that matter/energy is the uncreated thing. I do not wish to persuade someone that god doesn't exist. I wish to persuade someone from making a very bad logical argument.
If one argues that the level of observed complexity cannot come from randomness alone and therefore must have been created by an external actor, then how does the external actor have sufficient complexity to create the complex universe.
So going back to my notation of (U - things made) and (E - things not made).
If (E) made (U) then where did (E) get enough complexity?
The only conclusion is the complexity in (E) is eternal also.
In plain words, that would imply that if God exists, then He would be eternally complex of complexity >= universal complexity.
Thank you for pointing that out, that's cool to think about.
In the same my statement, "god's existence begs the question, who made him?" is not valid to you your question who made matter is not valid to me. The question implies creation and both of us believes that something wasn't created. We just differ on what thing is.
Both systems are logically consistent so there would need to be other reasons to choose one or the other.
If there is an (E) the only possible way we would have of knowing - would be if (E) communicated somehow and provided evidence.
Even if one considered complexity as evidence it would not be sufficient or specific about (E).
In my case, the evidence that leads me to conclude that (E) does exist has little to do with the complexity of life.
Anyway, thanks for your time and thoughts. I especially appreciate your insight about the requirement of eternal complexity in my point of view. That will give me something to think about for quite a while to ponder it's implications.
Let's suppose god exists and is extremely powerful and intelligent. The amount of information contained in the system god is vastly greater than on Earth. Thus by the statements you've made the probability of the god system being natural, that is not created by an intelligent agent, is orders of magnitude closer to zero than the system on Earth.
OK, so ID people will claim that god is the sole uncreated intelligence, or uncaused event. But they are at the same point no -ID people are at. Namely, that very complex systems can exist without being created.
But they, and this is expressed very well in the NOVA documentary about the Dover trial, always assume the components have to work as is in the end result. The bacterial flagellum, for example, is one of the examples they keep trotting out despite counter-examples of it used as an injection mechanism in bacteria, and other things.
To re-use the analogy from the documentary. They see organisms like mousetraps. And if any part is removed it no longer functions. That's true to an extent. It no longer functions as a mousetrap, but it could function for a variety of other things. The mousetrap is a flawed analogy because it does not pursue self-preservation, so it's easy to say "well it's useless now" from our perspective, but not so much when it comes to actual living things that we know little about.
That's not the argument from Phys.org which is just a online news organization, anyway.
Then your thinking is flawed, there is not "who", the process was not "created", it evolved. Nature is not a "who".
"program" size limited to 500 tiles IIRC, because the design will break when things get larger. Still amazing, happy googling.
Don't think of cells as disordered bags of water. They're more like highly ordered liquid crystals.
So there is this HUGE part of biophysics that we completely isolate all of the undergraduate students from, with these pretty videos where one machine magically swims out to exactly where it's supposed to go and then the next machine magically swims in to do the next thing and then the next machine, and so on, until you've got this perfect assembly line chugging away at this stuff. That is NOT what happens.
The reason that we make those "schematic" videos is that if we drew the real video, you could get overwhelmed by detail and miss the actual mechanism that we're talking about. What's actually happening is that this whole activity is happening in one big churning sea of all of these things knocking into each other bouncing around chaotically. That one machine that went to the right place is symbolic of hundreds of machines that happened to bounce off into the wrong one; that straight line is symbolic of an average of a million possible bouncy trajectories which went in all sorts of different directions before getting there. Everything is at a high enough concentration and pulsating and buzzing so much that in short order the "right stuff" happens to bounce together to do whatever is happening. Sometimes, even, the cell makes the "local concentration" of some machine or part even higher, via either containing some structure within a bag or else by producing proteins which attract "the right sort of thing" to them, so that more nucleotides or whatever happen to be nearby.
Just to give a more concrete example, in the fertilization of an ovum, we showed you a nice picture of one single solitary spermatozoon which shakes hands nicely with one ovum, and they became best friends. We also tried to scare you with "just one sperm is all it takes!" reasoning, which is technically true but misleading. If we were showing you the absolute truth, you'd see that the ovum is getting beaten down by a bunch of spermatozoa pelting it like a pack of wolves, trying to break down a chink in its shell, called the "corona radiata", until one of them burrows into a thin tear. Then the eggs of most mammals have to chemically shift composition of their borders to actively prevent "polyspermy", getting penetrated by multiple spermatozoa, through that tear. What's really fascinating here is that we're not completely sure how this happens because usually this process is happening during meiosis, another of those things where we separate the story for the textbooks ("meiosis happens, then you store the resulting cells, finally some of them bubble up for fertilization" -- no, meiosis actually has these two long pauses in it; long-term storage happens during the first one (the "dictyate") and fertilization happens during the second one before meiosis is complete). So it's hard to say "this prevention of polyspermy is due to meiosis" vs. "it's due to fertilization."
Suddenly it's not so much of a surprise that some of your friends were trying for years to conceive while some teenagers you know of got pregnant too soon -- that "it only takes one" rhetoric makes people very worried very rapidly, "what if I waited too long, what if I'm infertile" and the "there is literally a wall there and it's a matter of luck whether something breaks through it or not" story reveals the real emotional truth: "oh, we have like no real control over this; whatever will be, will be."
It's just that at the lowest levels there's a ton of bouncing chaotic pulsating activity, things smashing into each other routinely, and heck, the only reason that your proteins even keep their characteristic lumpy shapes is that they're designed by evolution to take on this shape when water molecules are bouncing against them chaotically enough that they happen to curl up into it. The machines to replicate DNA similarly are sitting in a sea of nucleotides smacking against them, which is why the helicase can't unzip too far ahead of the polymerase; that polymerase might be able to handle the stray nucleotide that binds prematurely to the DNA, but it might have real trouble if an extended sequence gets accidentally bound that way.
Inner Life of the Cell https://www.youtube.com/watch?v=FzcTgrxMzZk
And here's a nice TED talk by Drew Berry:
Animations of unseeable biology https://www.youtube.com/watch?v=WFCvkkDSfIU
These kind of visualizations are of course an idealized view on how it works. As others have already mentioned, the processes are hugely chaotic and much more probabilistic than deterministic. On this scale everything is just one huge wobbling soup of things crashing into each other, which makes it even more fascinating that it works as well as it does.
How are they delivered to the polymerase in the first place? How do they "know" where to be?
Are there just so many of them in the cytosol that through sheer numbers, there's enough random chance they'll just shuttle into place when the polymerase needs them?
Yes. Everything at that scale is very small, very close together and moving very, very fast.
This kind of thing is very common at the cellular level: have a receptor/channel/process/thing that only one precise 3d molecule can fit into - and then just wait.
As long as there's a process somewhere to make/acquire that molecule, then one will be along in a few nanoseconds or so, depending on the concentration. In the meantime the recipient will just wait.
In this way otherwise independent processes can regulate each other, and respond in a concentration dependant way to changing conditions without any central control.
But what if the molecule has an unexpected "tail" attached to it? How to prevent the process from getting stuck?
So something with an unexpected tail won't react. It will not occlude the receptor either because it won't bind with it reliably...
These things are very, very precise.
http://www.righto.com/2011/07/cells-are-very-fast-and-crowde...
Reading your description of cells as moving imperceptibly fast only fills me more with this sense—that we are very slow moving giants, waiting on the billions of "years" of inner machinery time to tick us forward ever so slowly.
I was actually thinking about putting a little video together about these scales of time, with the video containing nothing more than a person's blink reaction slowed down 5,000x.
I haven't had a book this good in some weeks. Cheers!
http://www.sciencedirect.com/science/article/pii/S0003347213...
European eel 0.23x
Leatherback sea turtle 0.25x
Blacknose shark 0.30x
Tokay gecko 0.33x
Rainbow trout 0.45x
Scalloped hammerhead 0.45x
Little skate 0.50x
Tiger salamander 0.50x
Harp seal 0.53x
Japanese rice fish 0.62x
Lemon shark 0.62x
Brown rat 0.65x
Green sea turtle 0.67x
Loggerhead sea turtle 0.67x
Great horned owl 0.75x
Tuatara 0.75x
Guinea pig 0.83x
Cat 0.92x
American red squirrel 1.00x
Homo sapiens 1.00x
Goldfish 1.12x
Anolis cristatellus 1.17x
Short-eared owl 1.17x
Budgerigar 1.23x
Dog 1.33x
Green iguana 1.33x
Yellowfin tuna 1.33x
Chicken 1.45x
Common treeshrew 1.50x
Rhesus macaque 1.58x
Common starling 1.67x
Rock dove 1.67x
Yellow-pine chipmunk 1.67x
Golden-mantled ground squirrel 2.00xThanks for the excellent blog post. This is something more people need to appreciate.
I never realized just how crowded until I saw David Goodsell's molecular illustrations[1] in Drew Barry's TED talk.[2] Goodsell's drawings show the actual density and diversity of molecules inside the cell.
[1] http://mgl.scripps.edu/people/goodsell/illustration/public
People get confused because they read that cells are ~99% water by molecule count. By weight they're only ~65-70% water. One out of three atoms being part of a non-water molecule means cells are tightly packed.
With that in mind I'd guess the bigger issue is how cells avoid having to deal with molecules being in the wrong spot.
Also interesting things, just for scale: see a bacterium and a cell nucleus: https://www.youtube.com/watch?v=mdhk_-o8_n8
And an actual protein diffusion measurement from inside a nucleus (via light emitting proteins): https://www.youtube.com/watch?v=cDxUmCPxP_E
So, we're still some time from getting a "real" picture of the nucleus. Mostly because it's so dense.
(Here's a video about single particle tracking on the plasma membrane https://www.youtube.com/watch?v=dlq3kkbskaA and the nucleus is at least a magnitude more dense/busy.)
Life is very much about density gradients. Ion channels, osmotic pressure, and so on.
40% of the cytoplasm is proteins (by volume), which is remarkably high, considering a naive lattice packing is just 34% (the tetrahedral lattice with a density of).
"...started watching individual DNA strands..." I'm wondering how important the visualization and nature of "filming" helped to form the idea or prove the hypothesis that replication is a async process. I didn't quite gather which is more impressive, the filming or the discovery.
“Sometimes the traffic in the next lane is moving faster and passing you, and then you pass it. But if you travel far enough you get to the same place at the same time.” also doesn't quite make sense to me as the video clearly shows no queuing structure as seen in real life traffic, and there is no real hypothesis to explain the sudden stops and starts.
Sorry, but is this really that new? I've never been taught that the DNA strands coordinate with each other while replicating, so it seems quite possible that synthesis of each strand can be independent of each other.
Couldn't that be the unintended effect of doing things in a flow chamber?
align: center
I suppose viruses do count as 'life' in some sense, so fair enough, thanks for clearing that up.
#neat
I don't doubt what they are saying, but that looks nothing like the models of DNA that are used as eye candy in movies and such.
This is zoomed out and fuzzy, such that you see a bunch of growing strands...not the detail of just one.
And just as fuzzy white lines, given the relative size and techniques used to make it visible.
Even in the best images that exist, all you are going to see are little bits that look like string.