5 ms·

Really like this analogy: It is a somewhat astonishing fact of life that the exact same DNA is shared by every cell in your body, from the skin to the brain; th

Really like this analogy: It is a somewhat astonishing fact of life that the exact same DNA is shared by every cell in your body, from the skin to the brain; those cells differ in appearance and function because, in each of them, a molecular gizmo “transcribes” some DNA segments rather than others into molecules of single-stranded RNA. These bits of RNA are in turn used as the blueprints for proteins, the molecular machines that do most of a cell’s work. If DNA is your phone’s home screen, then transcription is like tapping an icon. By sampling the RNA present in a group of cells, researchers can see which programs those cells are running at that moment; by sampling it after the cells have been infected with a virus, they can see how that virus substitutes its own software.

jcims 6y ago
'Molecular machines' is not an overstatement. Here's an example of some of them working in harmony to maintain an essential electrochemical gradient across the lipid bilayer that encapsulates the mitochondria: https://www.youtube.com/watch?v=LQmTKxI4Wn4 https://www.youtube.com/watch?v=LQmTKxI4Wn4 It's a 7 minute video, if you only have a little time, skip around, but make sure you listen to the part starting at 6:17. DNA isn't just the blueprint for the machine or the blueprint for the factory that makes the machine, it's the blueprint for the entire supply chain required to build and operate an entire chemical industry of mind-bending complexity. Like doubling grains of rice on each square of a checkerboard, if you wanted to create a complete catalog of all possible combinations of a string of DNA that's 150 base pairs long, you would have to marshal all of the estimated matter in the observable universe and you'd still end up short. Most of the genes that create these proteins are tens of thousands of base pairs in length and the entire human genome is ~3 billion.
- im3w1l 6y ago
  Thanks for posting this. Looked further into atp synthase. Absolutely amazing. A little turbine, driven by the flow of protons, spinning in 120 degree discrete clicks, around catalyst pockets, where each click changes the shape of the pocket to a new one. And after the pocket has gone through a complete cycle, adp and phosphate have been fused. Never seen the chemical (proton concentration), converted into something mechanical (spinning), and back into chemical (adp + phosphate -> atp) in such a way before.
  - jcims 6y ago
    ATP synthase is amazing. It uses the driving force from the potential gradient (aka voltage) built by the proton pump in the first video to spin at ~21,000 rpm and crank out ATP. I read that your body creates (and then consumes) about its own weight in ATP every day. This channel has a ton of great videos: https://www.youtube.com/user/WEHImovies/videos https://www.youtube.com/user/WEHImovies/videos Here's one on kinetichore and mitosis (which also shows kinesin and dynein which are comically odd) - https://www.youtube.com/watch?v=IvJrDsRuWxQ https://www.youtube.com/watch?v=IvJrDsRuWxQ There's a collection of their DNA ones here: https://www.youtube.com/watch?v=7Hk9jct2ozY https://www.youtube.com/watch?v=7Hk9jct2ozY Here's another view of the ATP synthesis process that shows the chaos a bit more: https://www.youtube.com/watch?v=OT5AXGS1aL8 https://www.youtube.com/watch?v=OT5AXGS1aL8 When I think of these systematically I just wonder what the intermediate steps were. The proton pump uses energy to create the potential gradient that ATP synthase runs on. You can't have a proton gradient without the proton pump, and without the proton gradient you don't have ATP. So these two exquisitely complex machines depend on each other and had to evolve together. It boggles my mind. Edit: Ah! Was looking for this one, sodium potassium pump - https://www.youtube.com/watch?v=ZKE8qK9UCrU https://www.youtube.com/watch?v=ZKE8qK9UCrU This is how our neurons propagate signals. They are driven by ATP.
    - AstralStorm 6y ago
      Immediate step is a cell which is long and has a natural ion gradient. E.g. one with flagella on just one side. Then the better ones would evolve machinery to speed up the gradient, which happened to be using some energy but made said cell move and digest faster, thus also reproduce faster. At this point this could still be shut down during lack of food or activity, as there was a natural gradient when activity was nearby. The membrane is the later invention, dating to organelles which are suspected to be microcellular parasites that got integrated and then reduced. These membranes were much more efficient, however they were very hard to turn off for hibernation as the membrane is a static gradient and hard to disrupt temporarily.
      - im3w1l 6y ago
- kitd 6y ago
  As a layman, I found "The Gene Machine" by Matt Ridley a fascinating exposition on how 'mechanical' genetics can be.
  - kitd 6y ago
    Apologies, it's "Genome" by that author: https://www.amazon.co.uk/Genome-Autobiography-Species-23-Chapters/dp/185702835X https://www.amazon.co.uk/Genome-Autobiography-Species-23-Cha...
ramraj07 6y ago
Good analogy, but there are some differences - your cells are not running one app, but just tens of thousands of routines with no clear definition of which routine is doing what function (many do multiple functions often with mix-match redundancy). And the mere fact that a routine is running is not enough, their activation state (posttranslational modifications, folding configurations, binding partners) or the values of all its internal variables is also important to know the exact function of each routine. Even that is only theoretical - we generally know some level of detail to know what many of these routines are approximately up to, but rarely in the detail needed to figure out what a cell is up to in general. In some ways studying what a cell is upto using our current methods is comparable in certainty to how we poll the US before elections.
dd36 6y ago
https://www.nytimes.com/2018/05/21/science/mosaicism-dna-genome-cancer.html https://www.nytimes.com/2018/05/21/science/mosaicism-dna-gen... That’s not exactly true. https://www.nytimes.com/2019/12/12/science/chimera-bone-marrow-dna-semen.html https://www.nytimes.com/2019/12/12/science/chimera-bone-marr...
refurb 6y ago
The really mind blowing thing is not just that DNA encodes everything for a living organism, but that it also has all the necessary elements to control expression so the right thing gets made at the right time in the right place. The fun part is that it's not like DNA is just expressed, it needs to be "unwound" from it's natural state as a highly dense structure. Elements within the cell actually regulate the unwinding itself, that's one way genes are turn on/off. And in addition, once DNA is unwound, split into a single strand and transcribed into RNA, the RNA itself becomes a regulating mechanism through siRNA. So the very act of transcribing DNA has regulating effect up the transcribing itself.
- usrusr 6y ago
  Conjures up a mental image of a computer where the only mutable state is instruction pointers for parallel threads. Not quite accurate, but a rough ballpark to how crazy those "programs" must be. (If for some reason we had to work with that kind of computer we'd probably enforce a conventional, graspable approach on it by finding a way to simulate a conventional computer once and then conveniently forget about the underlying madness, clearly that wouldn't be the path taken by evolution)
thro1 6y ago
AFAIK every neuron cell in the brain has (minimally) different DNA.

jcims 6y ago

'Molecular machines' is not an overstatement. Here's an example of some of them working in harmony to maintain an essential electrochemical gradient across the lipid bilayer that encapsulates the mitochondria: https://www.youtube.com/watch?v=LQmTKxI4Wn4 https://www.youtube.com/watch?v=LQmTKxI4Wn4 It's a 7 minute video, if you only have a little time, skip around, but make sure you listen to the part starting at 6:17. DNA isn't just the blueprint for the machine or the blueprint for the factory that makes the machine, it's the blueprint for the entire supply chain required to build and operate an entire chemical industry of mind-bending complexity. Like doubling grains of rice on each square of a checkerboard, if you wanted to create a complete catalog of all possible combinations of a string of DNA that's 150 base pairs long, you would have to marshal all of the estimated matter in the observable universe and you'd still end up short. Most of the genes that create these proteins are tens of thousands of base pairs in length and the entire human genome is ~3 billion.

im3w1l 6y ago
Thanks for posting this. Looked further into atp synthase. Absolutely amazing. A little turbine, driven by the flow of protons, spinning in 120 degree discrete clicks, around catalyst pockets, where each click changes the shape of the pocket to a new one. And after the pocket has gone through a complete cycle, adp and phosphate have been fused. Never seen the chemical (proton concentration), converted into something mechanical (spinning), and back into chemical (adp + phosphate -> atp) in such a way before.
- jcims 6y ago
  ATP synthase is amazing. It uses the driving force from the potential gradient (aka voltage) built by the proton pump in the first video to spin at ~21,000 rpm and crank out ATP. I read that your body creates (and then consumes) about its own weight in ATP every day. This channel has a ton of great videos: https://www.youtube.com/user/WEHImovies/videos https://www.youtube.com/user/WEHImovies/videos Here's one on kinetichore and mitosis (which also shows kinesin and dynein which are comically odd) - https://www.youtube.com/watch?v=IvJrDsRuWxQ https://www.youtube.com/watch?v=IvJrDsRuWxQ There's a collection of their DNA ones here: https://www.youtube.com/watch?v=7Hk9jct2ozY https://www.youtube.com/watch?v=7Hk9jct2ozY Here's another view of the ATP synthesis process that shows the chaos a bit more: https://www.youtube.com/watch?v=OT5AXGS1aL8 https://www.youtube.com/watch?v=OT5AXGS1aL8 When I think of these systematically I just wonder what the intermediate steps were. The proton pump uses energy to create the potential gradient that ATP synthase runs on. You can't have a proton gradient without the proton pump, and without the proton gradient you don't have ATP. So these two exquisitely complex machines depend on each other and had to evolve together. It boggles my mind. Edit: Ah! Was looking for this one, sodium potassium pump - https://www.youtube.com/watch?v=ZKE8qK9UCrU https://www.youtube.com/watch?v=ZKE8qK9UCrU This is how our neurons propagate signals. They are driven by ATP.
  - AstralStorm 6y ago
    Immediate step is a cell which is long and has a natural ion gradient. E.g. one with flagella on just one side. Then the better ones would evolve machinery to speed up the gradient, which happened to be using some energy but made said cell move and digest faster, thus also reproduce faster. At this point this could still be shut down during lack of food or activity, as there was a natural gradient when activity was nearby. The membrane is the later invention, dating to organelles which are suspected to be microcellular parasites that got integrated and then reduced. These membranes were much more efficient, however they were very hard to turn off for hibernation as the membrane is a static gradient and hard to disrupt temporarily.
    - im3w1l 6y ago
kitd 6y ago
As a layman, I found "The Gene Machine" by Matt Ridley a fascinating exposition on how 'mechanical' genetics can be.
- kitd 6y ago
  Apologies, it's "Genome" by that author: https://www.amazon.co.uk/Genome-Autobiography-Species-23-Chapters/dp/185702835X https://www.amazon.co.uk/Genome-Autobiography-Species-23-Cha...

ramraj07 6y ago

Good analogy, but there are some differences - your cells are not running one app, but just tens of thousands of routines with no clear definition of which routine is doing what function (many do multiple functions often with mix-match redundancy). And the mere fact that a routine is running is not enough, their activation state (posttranslational modifications, folding configurations, binding partners) or the values of all its internal variables is also important to know the exact function of each routine. Even that is only theoretical - we generally know some level of detail to know what many of these routines are approximately up to, but rarely in the detail needed to figure out what a cell is up to in general. In some ways studying what a cell is upto using our current methods is comparable in certainty to how we poll the US before elections.

dd36 6y ago

https://www.nytimes.com/2018/05/21/science/mosaicism-dna-genome-cancer.html https://www.nytimes.com/2018/05/21/science/mosaicism-dna-gen... That’s not exactly true. https://www.nytimes.com/2019/12/12/science/chimera-bone-marrow-dna-semen.html https://www.nytimes.com/2019/12/12/science/chimera-bone-marr...

refurb 6y ago

The really mind blowing thing is not just that DNA encodes everything for a living organism, but that it also has all the necessary elements to control expression so the right thing gets made at the right time in the right place. The fun part is that it's not like DNA is just expressed, it needs to be "unwound" from it's natural state as a highly dense structure. Elements within the cell actually regulate the unwinding itself, that's one way genes are turn on/off. And in addition, once DNA is unwound, split into a single strand and transcribed into RNA, the RNA itself becomes a regulating mechanism through siRNA. So the very act of transcribing DNA has regulating effect up the transcribing itself.

usrusr 6y ago
Conjures up a mental image of a computer where the only mutable state is instruction pointers for parallel threads. Not quite accurate, but a rough ballpark to how crazy those "programs" must be. (If for some reason we had to work with that kind of computer we'd probably enforce a conventional, graspable approach on it by finding a way to simulate a conventional computer once and then conveniently forget about the underlying madness, clearly that wouldn't be the path taken by evolution)

thro1 6y ago

AFAIK every neuron cell in the brain has (minimally) different DNA.