Wise words a former cell biology aware PhD said to me once: a cell is at a scale where van der Waals forces means 'water' isn't behaving like you think and the 'liquid' of a cell is possibly more like a matrix than a fluid. Those high school cell models are very misleading. He basically said macro scale intuition was useless for what it means to pierce the cell wall, as an example. What does "pierce" even mean?
Want to point out that this still slightly depends on what cell you are talking about - a mammalian cell is a thousand times larger than a bacterial cell, which in turn is a hundred or thousand times larger than a virus. An apt comparison is if you were a cell in your body, a bacteria is at best the size of a pea and a virus the size of an ant. Viruses are so small that you can sometimes just crystallize them to study their structure with crystallography as if the entire thing is a single molecule.
The GP is right in that our intuitions aren't cutting it down at the bottom.
All these animations tend to edit out the water molecules so that the audience can understand better. The proteins aren't colored blobs at all. At these scales you'd clearly see individual atoms instead of blobs. But watching a bunch of really detailed atomic ball-stick models would be confusing. And not only are the H2Os battering everything like TIE fighters in the Hoth asteroid field [0], there are ions in there too (Na, K, Cl, etc) that really effect the cell. The membranes are also edited, as many cells are porcupined with receptors like an over crowded wave pool [1]. In addition to the water/saline being edited out, most of the other proteins, vesicles, and interior membranes are also gone for the sake of clarity. There is nearly no free 'space' in the cell, think of a really crammed subway car [2], with the air being like the water/saline. But only much much tighter.
The cell is more like a frantically efficient liquidy crystaly thingy than a wonky wobbly blobby poofed-up juice box. And each one is utterly deeply profoundly fascinating.
I think David Goodsell's beautiful paintings, in his book Machinery of Life, were the first serious attempt to depict how crammed a cell is (page down past the pictures of individual molecules to get the the cell cross-sections):
The other thing missing from those videos is any indication of how random these processes are. At one point, an actin filament assembles by having monomers fly directly at the tip and stack neatly together. It's not like that. In reality, there are all sorts of molecules just randomly moshing around, and occasionally, an actin monomer will bump into the tip of the filament and stick, because it has a binding site. But sometimes one will bump into the tip and not stick! Sometimes, the tip of the filament will fall off! The growth is purely statistical: monomers are more likely to stick than to fall off, and more likely to stick than some random unrelated protein is to stick.
Pity I only get 1 upvote. I'd triple-click if I could.
This animation enables one to visualize a single SARS-CoV-2 virion binding with the ACE2 enzyme, entering the host cell, and replicating 4-5 new virions.
One SARS-CoV-2 virion is 125 nanometers wide. By the time it shows up on a CT scan we are talking many, many billions.
It's seems impossible anyone could test positive and still be asymptomatic.
> It's seems impossible anyone could test positive and still be asymptomatic.
Why? Most symptoms are part of the body's response switching into overdrive and not a direct consequence of cells getting subverted into virion farms. If the immune system wins without resorting to state of emergency measures like a fever you won't notice, but in the meantime there is a phase of viral replication in the throat.
With SARS-Cov-2 there is even the pattern that detection drops already in the throat of patients that still have a pneumonia raging in their lung (probably because the throat, as a battlefield in this war, somehow favors the immune system more than the lung?), so it's not even a subset/superset relation between symptoms and positive throat PCR, it's a partial overlap.
Seems impossible but from observation obviously is not.
Comorbidity is the issue with SARS-CoV-2. It is interesting that some patients testing positive report losing the sense of taste and/or smell while others report digestive problems prior to the onset of acute respiratory problems or even sore throat.
I note that the virus depicted in the animation is HIV. How much of the lifecycle is different from HIV to SARS-CoV-2? One thing I noted is that it said the inserted viral DNA might remain dormant for years; surely that part is HIV-specific? (Or do we really bear viral infections for years after recovery, and—I presume—rely on the continued presence of antibodies to quash the remaining DNA?)
That part is mostly specific to retroviruses and DNA viruses. Retroviruses are special because even though they are RNA based they can "translate" their RNA into dna once inside the cell and embed that DNA into the cell's genome. That translation in itself is remarkable since it's the opposite of the normal DNA to RNA "translation" we see in almost every organism, hence the "retro".
DNA based viruses don't have that unique mechanism but the result is conceptually the same: you get a virus that is extremely hard to completely cure/remove due to it being present in some of your own DNA. Herpes is a DNA based virus and that's why you can't ever be fully cured from it.
That's also why retroviruses like HIV can only be suppressed. It's also why antiretroviral drugs try to inhibit the replication phases of the virus, which makes managing the disease possible but can't remove the virus itself. Still, a cocktail of those inhibitors is an amazingly powerful treatment against AIDS and leads to HIV becoming basically dorment in the body.
A ribovirus (which is what coronaviruses are) is RNA based but it doesn't embed itself into our genome. It never translates it's RNA and since RNA is fundamentally less stable of a molecule than DNA, you get really high mutation rates. That "instability" is caused by the lack of a built in error checking mechanism in RNA. Those random mutations are part of why Influenza is hard to build immunity against. But it's also why RNA based viruses are generally either too virulent and mortal to allow for effective spread, or rapidly evolve towards less lethal forms.
Keep in mind that I've generalized a lot and that there are a lot of exceptions and outliers when it comes to viruses. For example, Hepatitis C is a ribovirus but it has a special protection mechanism that protects it's core genetic material from mutations even if it's RNA based.
> It never translates it's RNA and since RNA is fundamentally less stable of a molecule than DNA, you get really high mutation rates. That "instability" is caused by the lack of a built in error checking mechanism in RNA.
The coronovirues have a proofreader mechanism, which is interesting.
Yep! That's what really makes influenza special, as I said the mutation rates are only part of why Influenza viruses rapidly change. Their ability to cross between species by combining easily with other types of influenza viruses are the key to their incredible variability
One of the distinguishing trait of CoVs are their special RNA replication/transcription mechanisms that results in less errors, which is really important considering the large size of their genomes compared to other RNA based viruses. Though, and correct me if I'm wrong, aren't they still extremely less stable than DNA viruses? Which is why only short/medium term immunity is usually possible? I don't know a lot about the synthesis of coronavirus RNA but it looks super interesting
> Though, and correct me if I'm wrong, aren't they still extremely less stable than DNA viruses?
That's correct. Worse, the proofreader doesn't have to protect all parts equally...
> Which is why only short/medium term immunity is usually possible?
No. For some viruses active immunity just doesn't last particularly long for reasons we don't understand (or at least it was described as not understood in every paper I've seen on the subject). For some viruses you can be reinfected months later with exactly the same virus. This is the case for several cold causing viruses.
Amazing. The mind boggles at how complex this is and the fact that humans have the tools to discover and understand the process. Thank you very much for sharing!
I picked up a microscope last year - they were on sale, and one of those things I'd always wanted to have a play with. I remember having a look with them in school and never seeing much and it seemed very hard.
All you have to do is go to a pond or creek scoop out some weeds, dirt and water and stick it in a jar and there is hours of exploration in front of you. Once you start looking its like seeing an evolutionary world in front of you, everythings eating each other and trying to not be eaten. If you're thinking of getting a telescope (I had one), think of a microscope they open up a new world, its incredibly easy to see things - I thought it would be a lot more work.
one of my greatest confusions of "life" is why there is this need to consume or feed off of or battle against other life. what is the purpose of this drive? why is it like this? i suspect the answer lies in thermodybamics and/or information theory, but it would be amazing to understand the reason behind life's battles for survival.
My friend built a house. I wanted a house. It was easier to take the lumber from his house than cut down trees and mine iron for nails. Eating another is no different. Different life evolves to take a niche item (like grass or minerals) and turn it into something useful to them (muscle and fat) that is also useful to others.
Are there really that many other ways? Photosynthesis, sure, but that doesn't seem to produce much and doesnt allow much "liveliness".
Anyway...
The 'why' is trivial-seeming to me. Once one organism can consume ready-made nutrients from another organism for less energy cost than producing, it will, or it will be out competed by others who do. So carnivores exist everywhere. Even deer happily eat baby birds that they come across, and rabbits eat their own.
Because the amount of energy that is available increases the further down the food chain you go. Photosynthesis provides a small amount of energy, hence why plants and plantlike organisms tend to be either totally stationary or don't move much on their own.
Organisms that consume plants are capable of more complex behaviour and growth because the amount of energy and nutrients etc. is greater that they receive by conauming things that photosynthesize.
the analogy seems fine to me, if a bit anthropocentric.
every living organism has some way of perpetuating itself, either by growing indefinitely or by making copies of itself. there's no reason "why", other than that organisms that can't do this get filtered out very early in the game. this implies having some sort of "strategy" for traveling up the energy gradient.
short of somehow evolving the biological capability to fuse/split atoms, all the usable energy on earth comes from the sun. so the first link in the chain has to be something like photosynthesis, where you collect and store energy directly from the sun (ie, "building a house"). but in doing this, you change the gradient, creating an opportunity for other organisms take your stored energy for themselves. in some sense, it's much "easier" for a rabbit to eat a plant in one minute than it was for the plant to collect all that energy over its entire life. there's only so much solar radiation per square meter, which limits a plants energy budget. a rabbit can eat many plants in a day, effectively multiplying the area of the solar radiation it can capture (and spend on acquiring even more). but then the rabbit creates an opportunity for a predator to harvest its stored energy and the cycle continues...
it seems like you're maybe asking "why can't all life just cooperate"? this would probably look like a planet full of plants (or a similar lifeform at a different scale). the problem is that this leaves a huge opening for the first "defector"; it's an unstable equilibrium. life does not evolve to leave opportunities on the table.
Look into "dissipative structures", which are indeed closely linked to thermodynamics.
In short, energy gradients (ie, on hydrothermal vents) can cause matter to organize itself into structures that more efficiently dissipate this energy. You can see how the creation of this structure would in turn enable the creation of a new kind of structure that lives on top of that.
There are competing processes in nature even without life (in the usual sense of the word) - atomic nucleus fission/fusion, light absorption/emission, crystal nucleation vs. decay, molecule synthesis vs molecule decay - each process operating towards getting more ground. Life fighting (or helping) other life can be looked upon as a more complex variant of the same process dynamics: one set of atoms and processes interacting with other set of atoms and processes, sometimes this looks like cooperation, sometimes like a battle.
Actually game theory is probably the better place to look. Though the concept of natural selection already tends to cover the big picture. Organisms need resources to reproduce. Those that can obtain more resources (or use what they have more efficiently) reproduce more and eventually drown out those who cannot reproduce as much. Taking from another organism (whether by hunting, parasitism, etc) is just one way of obtaining more resources.
Thats probably the thing I learnt looking through the microscope, or was perhaps made obvious. Life at that level is just chemical gradients and finding bio mass to procreate, so things that don't do this don't procreate and die, the winners are the ones that are the best at this. The asking why is a human thing and is so many layers on this elementary life we can afford to ask these questions, but I don't think life can exist without competition, at least not organic life that has evolved. Maybe we'll make a more pure sort of life that doesn't need competition to grow but not sure about that.
Another interesting thing: cells are packed so tightly (not just a bag of water) that proteins grind against each other and against their ligands, increasing the "activity" (even the free energy of ATP hydrolysis isn't the standard 7.3kcal/mol.
Yes, macro-scale intuition isn't great (although people pierce cell walls with tiny needles all the time), but if you spend enough time looking at cells under a microscope, you start to build an intuition about cell and molecule behavior.
Also, on that scale individual molecules are bouncing around inside the cell faster than you can run or bike. It is a metaphorical froth of seething sliding movement.
I think this was first written about at length in the book ‘Soft Machines’, which is a really good critique of some of the nanotechnology thinking at the time. I highly recommend the book.
Actually it was a terrible critique of nanotechnology, which doesn’t try to make things the same way as biology. But a good overview of the funkiness which comes part and parcel with life’s microbiology.
Not sure which field of bionanotechnology (I assume you meant bionanotechnology ) you work in, but for the one I work in, the metaphor of biology and computer science is extremely intertwined—like very explicitly. Circuits, computation, the whole nine yards. If you’re talking about graphene or something that is an entirely different field. I can’t see how this book was a terrible critique of bionanotechnology—or at least an excellent discussion of the hardships faced.
I did not mean bionanotechnology, and neither did Smalley. He offered that as a critique against Drexlar’s diamondoid molecular manufacturing, in a successful political coup to claim the billions in research dollars that were promised as part of the National Nanotechnology Initiative.
Because of Richard Smalley that money went towards material science and chemical research instead of the molecular manufacturing it was promised for. Even though, as you point out, in terms of fact the critique only applied to life-like bionanotechnology.
The history of this is laid out pretty well—with a surprisingly minimal amount of sour grapes—in Drexler‘s book Radical Abundance.
Is there a a good read on how RNA and DNA work for a Computer Scientist? And more generally how biology, genetics, epigenetics, virus, etc work?
Many vulgarization sources say that DNA is like the source code of life. But they mostly skim across the issue and go to conclusions like "this gene or set of genes are responsible for that outcome".
But coming from a CS background that sounds a bit like non-sense. I feel like it is like saying that "this processor instruction is responsible for that outcome". But in the end what is important is not the individual instruction but the interaction between them and the environment (Input / Ouput).
I wouldn't recommend trying to understand it through analogy to CS - I'm a biologist and know enough CS to feel uncomfortable really using any of the usual analogies. The problem is that they work ok for a layperson understanding, but are fundamentally wrong enough that if you want to understand it at the level of something like virology you'll be lead constantly astray. I dont know of a better recommendation than "watch some recorder bio 101 lectures or pick up a textbook, and learn it like a bio major instead of a CS major." It's a lot of time commitment, but I think you have to put in the time to actually learn it from first principles.
For context, imagine if I as a biologist asked you, what's a good read on CS for a biologist? And generally how algorithms, data science, AI, and operating systems work?
You can understand why it would be difficult to recommend any readings on it. For me to learn to code at any level, I had to spend the time learning it from the fundamentals, and it was worth spending the time for me as it was far more rewarding than trying to wrap my mind around something like "so imagine source code is this thing that's like DNA + epigenetics + dna topology that codes for the information you want, but instead of a complex set of chemical and physical interactions, it's math, and you can change it at will and nothing is leaky on purpose, and the code you write doesnt evolve unless you tell it to which you might want to do sometimes for AI stuff, but usually not."
For example, the covid-19 virus's RNA ends with AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA (33 As) which, as someone pointed out, looks suspicially like a "NOP sled"[1] (i.e. so that a protein coming in hot can hit anywhere on the sled and then slide down to the actual information)
A poly A tail is at the end of the transcript, not the start. This is a perfect example of the dangers of analogies because this one is completely incorrect. Poly A tails protect RNA from degradation. A ribosome will not bind to that part, it will bind to something within the 5' untranslated region on the other end of the genome) ribosome binding site, kozak consensus sequence, etc). If you bound to the poly A tail and slide "down," you'd just slide right off the end of the gene.
Definitely nothing wrong with trying to find things that look similar across fields and try and gain differentiated insights, it's certainly an admirable thing and an important part of making many discoveries. But a first principles understanding of the structure of DNA, what a 5' end and a 3' end is, and how transcription/translation works (all bio 101 type stuff) would provide a much better foundation to do that with. You don't need a degree in biology to know the basics, just like you don't need a degree in CS to know the basics, but it's worth learning the basics if you want to get an understanding of the field or work with it.
It’s hard to disagree with what your saying, but analogies are fun.
I think the best analogy is DNA is a series of automated assembly lines. The workers, raw materials, and signals to turn sections on or off are separate. Each nucleotide station is called A, T, C, or G and adds a single element at a time to long chains which then get folded up into useful tools. DNA can also be used to manufacture either more stands of DNA or to do very simple repairs.
Alternatively, a stack of computer punch cards with a program on them. In that it’s a standard format for information transfer that is physically altered by the message it carries. Further, on it’s own nothing happens but connected to the right machinery it’s useful.
Edit - I'll concede that analogies are absolutely fun haha. They might be useful to come up with when you yourself are trying to better understand something by drawing connections to other things you know and all. But I don't think they're ideal for being taught the subject. And again, for a layperson, analogies are totally fine if you just want a surface level understanding of "oh, mitochondrias are powerhouses of the cell." But if you want to do anything with that, beware the dangers.
The second analogy is ok, but again not really great if you want to understand what's actually going on. If you just want to get an intuition that DNA has something to do with storing information, as long as that comes with an understanding that information evolves (biology is really the study of evolution in many ways), that's probably more than enough for a layperson. But it's a dangerous understanding if you plan on using it as a foundation to try and explore more complicated topics in biology. There's no need to do so, but if you are going to, it's far far better to spend the time getting the correct first-principles understanding and get rid of this idea of "DNA as source code" so you can better grapple with the subject.
I don't think the first analogy makes much sense since it makes nucleotides the sort of active agents here and needlessly focuses on individual nucleotides when codon triplets are what are involved in coding for proteins (probably better to, if you have to use an analogy, treat nucleotides as letters instead of words). And, especially in the context of this thread, neither analogy build the understanding needed to really dive into what RNA is, which is important for understanding what RNA viruses are, and what the coronavirus is.
The problem with including codons in such a high level analogy of DNA is their context sensitive. DNA doesn’t care about those details and can be sliced an diced to completely change how it’s interpreted.
Also, you really should include activation sites etc, but soon your out of the realms of analogy and just describing the details.
The big component missing in the analogy is gene expression. That’s what makes DNA behave differently from simple instruction mappings.
I guess we could visualize it as a series of drains, where the size of the hole can be modulated. Since gene expression can decrease or increase the rate at which DNA is transcribed
I have been using this for a while. What would you suggest instead of:
> The workers, raw materials, and signals to turn sections on or off are separate.
People are used to the idea of thermostats using on/off to maintain temperature which is not a terrible association. As you say gene expression is different, but I can’t find a better analogy.
That's why I figured an analogy would include nucleotides as letters that make up words rather than acting on their own to be able to encompass all that (and I love that in trying to help craft better analogies in a chain where im also railing against analogies)
And it also doesn't contain all of the source code and the error correction is when it tries to copy itself? I mean, just thinking of it as a type of biological source code that makes more of itself with mistakes and is messy is a decent enough analogy, and again I think most of these are fine just to be able to know as a layperson "oh right, DNA is that thing that has a lot of information about what the living thing is going to be like." You don't really need to know more than that day to day as long as other people do - I don't know how to fix my car but i know there are people out there that know how it works. If you are going to be more involved with it or want to know more about it for whatever reason though it's maybe worth diving into the bio 101 stuff then.
I dont actually know of any. I've heard of like biostar and maybe a couple others but I dont know how good those are. Researchgate is kind of a forum I guess? But most of the questions I've seen in the social media side of that are like "how do I turn this experiment"
I think most of the discussions I've had have been journal clubs during lab meetings. An hn style website for virtual journal clubs would be super cool...
IMHO, biology is most easily looked at as a recipe for order, from whatever ingredients happen to be laying around.
Essentially, everything is in the service of increasing order. And maintaining it.
Polymerase creates more genetic code out of raw ingredients.
Genetic code creates proteins.
Proteins perform all kinds of functions by leveraging physics and chemistry.
Membranes prevent all of this from being blown away and scattered in the chemical equivalent of a slight breeze.
... so, as you ask, 'Why genetic material in the first place?'
And to that, something of a tautology: because reproducing order reproduces.
Randomly assembled self-assembling assemblages constitute the major components of our environment, because everything else... didn't.
A rock is still one rock. Water is still water.
A blade of grass is now a meadow. A tree, a forest. A slightly intelligent primate, civilization as we know it. And a single mutated coronavirus, a pandemic in every country on the globe.
To me, what blows most comparisons and analogies out of the water, is the insane complexity to it all. That genes can influence and interact with each other. So gene expression (= gene -> protein) can change gene expression, e.g. based on environmental factors or folding of DNA etc...
Gene A is responsible for property A is way way way too simplified.
I have a microbiology degree and an EE degree (but more like comp E).
DNA truly is a blue print. (almost) Every cell in your body has the source code for your entire body.
"this gene or set of genes are responsible for that outcome" is generally going to be a true statement.
The equivalent wouldnt necessarily be a processor instruction.
If you wanted an analogy, a cell is like an entire minimal computer. Power supply, processor, memory, and I/O. Each computer can run different parts of the code, but every computer has the entire code base.
Within the computer are specialized "organelles" for storage, graphics, network, etc. These are comparable to organelles such as mitochondria, nucleus, endoplasmic reticulum etc.
DNA acts like code in that it produces outputs (messages) and receives inputs. Proteins are also like code in that they produce outputs and receive inputs.
It might be that DNA is like the executable source code that is stored as files and proteins are more like in memory processes such as services and actively running programs that get spawned from the files to perform various tasks.
Viruses are like hostile code in bound in an email or coming through as tainted packets. They cant actually do anything on their own - they are inert, but once the processor starts executing the code, they hijack the processor. Sometimes to spawn more malicious code to other computers in a trusted network
To carry the analogy further, departments in a company are a bit like organs. The computers in that department all roughly do the same thing. Imagine if IT imaged every computer in the company the exact same way, but what software was actually used would be based on your department.
The reason why CS analogies don't work very well is that molecular biology is very context driven, and we often don't know what the context is.
For example, in eukaryotes, the same piece of DNA can can produce different amounts of different proteins (i.e. with different amino acid sequences and different post-translational modifications), depending on things like DNA methylation (there's a number of different types), genomic location, accessibility, transcript methylation, multiple mRNA isoforms - the list goes on. A combination of these and other still unknown factors produces the final product, which may vary within a cell, between cells in a tissue, and between tissues.
Things behave consistently and predictability, except when they don't. Makes the field interesting and frustrating.
Analogies obviously don't hold for many cases. But it's a good entry point to explain some basic concepts such as the Central Dogma. I am a biologist who has to teach molecular biology to computer scientists in our Bioinformatics department. It was the only way to bridge the gap. Once we got it we could start on the more detailed stuff.
Biophys grad student here. If I'm understanding your frustration correctly, you're basically saying: "yes for the 1000th time, I KNOW DNA is the recipe book, but who is the chef?" Well, I'm sorry to report that there are a lot of chefs. And to make things worse, every cell is different, so there are also a lot of restaurants. For this reason, it is not possible to make a book on any of the topics you listed above without skimming.
The solution to this is narrow your scope: is there a particular subtopic that interests you?
I have discussed this exact analogy with a couple colleagues from a CS background. If someone said the genome is the source code that's very wrong. The more accurate analogy is that your genome is a compiled, highly compressed executable file (more or less 200 MB in size?) Where the optimizer blindly reuses variables and memory locations for multiple routines that may or may not be related. It probably is quite similar to oracle's DB2 codebase, where all this shit is in C, and you change some variable here and hell breaks loose somewhere else. For the most part though, if you don't tinker with it, it runs like a well oiled machine because a blind watchmaker programmer (with great intuition but no CS organization fundamentals) has debugged and patched it for billions of years, patch on top of patch millions of times over.
It's like writing ultimate spaghetti code in a dynamic language.
The nature of biology is much like classes and data floating around and all seemingly randomly interacting with each other, because ultimately this is just chemistry with thousands of unique compounds, which makes things messy.
But through natural selection it seems to work. Like a totally incomprehensible compression algorithm learned by neural nets or evolved by genetic code. There should be a source somewhere around here...
Once I tried to learn this stuff by asking a biochemist, but I soon became frustrated because it seems there are no 100% rules, only "it is usually like this" all the way down.
Like, did they teach you at school that eukaryotes have two sets of chromozomes, one from each parent? Yeah, "usually". But then also:
https://en.wikipedia.org/wiki/Polyploidy
>It's like writing ultimate spaghetti code in a dynamic language.
The nature of biology is much like classes and data floating around and all seemingly randomly interacting with each other, because ultimately this is just chemistry with thousands of unique compounds, which makes things messy.
It should be noted that biological systems were one of the exlicit inspirations for extremely dynamic and object oriented languages like smalltalk.
Far from being a negative aspect the 'centerless' design and high degree of decentralization is messy, but also extremely robust.The internet as a whole is another example of a human technology that utilizes that sort of design.
Proteins are built out of a chain of aminoacids. There are 20 different kinds of aminoacid, and the particular sequence of aminoacids determines the shape of the protein, and therefore its biological function.
To build a protein, the cell uses a strand of RNA as template. The RNA consists of a sequence of 4 kinds of bases (A=Adenine, C=Cytosine, G=Guanine, U=Uracyl) and there is a genetic code that maps each group of 3 RNA bases into one aminoacid. For example, "AGC" corresponds to serine, "AAG" means lysine, and "AGCAAG" means serine followed by lysine.
DNA is built of similar pieces as RNA. The main difference is that RNA is single stranded, while DNA is double stranded with that famous double helix structure. Additionally, DNA uses T=Thymine in place of U=Uracyl.
DNA acts a store of information. Each gene contains the genetic sequence that describes how to build one protein. When a gene is active, the cell copies that part of the DNA into a messenger RNA, and then uses that RNA as a template to build the protein in question.
Every cell in the body has the exact same set of genes, but they differ in what genes are active at each time.
------------------------------------
Now on to viruses...
The Coronavidus is an RNA virus. Each individual virius is a little ball made of proteins and lipids, encasing a genome made of RNA.
By itself the virus is inert, but once that RNA finds its way to inside a human cell, it behaves like a fork bomb. The cell translates the viral RNA into proteins, just like it would with our own RNA. One of the proteins is a polimerase enzyme, which then makes even more copies of the viral genome. Soon, there are thousands of copies of the virus. Additionally, the viral genome also encodes the structural proteins for the capsule of the virus, including the "spike" protein that gives coronaviruses their signature look.
The polymerase in most RNA viruses is an RNA-dependent RNA polymerase, an enzyme that makes copies of RNA. So what happens is: a single piece of viral RNA comes in the cell. Then it gets translated by the cell machinery, producing the polymerase enzyme. That polymerase then makes more copies of the viral genome. Which in turn gets translated into even more polymerase. Which then make even more copies of the virus... That is where the fork bomb analogy comes in.
That kind of thing doesn't normally happen to us because we don't have those enzymes that can make copies of their own messenger RNA. Putting those fork bombs in production would be asking for trouble :)
Humans have developed protections against some rogue RNA, since out of control fork bombs randomly happening isn't a thing that makes you successful at reproduction.
The Virus reproduces using a fork bomb but for us it's deadly.
I listened to the Great Courses audiobook about Biology. There's a lot about how the machinery of the cell works, how it evolved, and so on. He goes through everything else as well, including the immune system, ecology, and so on. It all ties together.
Regarding the genes and central dogma, he gives a LOT of detail about how for instance it was discovered that codons work in threes (not twos or fours). Also how it was discovered that DNA is the thing with the code, how the transcription process works, how the different kinds of RNA are involved, all the way to how the protein comes out.
The audiobook also comes with a downloadable book in case you'd rather read it.
> Many vulgarization sources say that DNA is like the source code of life.
DNA is a tape archive of files (genes). They are not binary (base-2) encoded, but base-4 encoded. A reading head (polymerase) reads sections of the tape and copies them into working memory. A 3D printer (ribosome) receives these sections from the working memory and prints nano machines (proteins) based on these tape snippets. DNA is not source code, it does not contain conditions or jumps (loops), it's data for the 3D printer. (Actually it's just a 1D printer, but the result folds into a 3D shape).
I have a CS background and for me the best explanation of how life fundamentally works was the MIT 7.00x "Introduction to Biology - The Secret of Life" course. It is absolutely amazing, requires only high school level knowledge and covers so many incredible stuff that I cannot possibly list all of it here. And not only is this course teaching you how stuff works but also the history behind it, how we, humans, figured it out. And, it's free and available online!
If you ever wanted to get deeper into biology than reading news articles, I cannot recommend this course enough.
The cell is an analog computer, but one who's computational state we are still working out describing (it consists of the concentrations of transcription factors as well as epigenetic modifications of DNA and chromatin), and who's evolution in time is governed by simple binding and enzyme kinetics, but that are integrated into networks that can be very complicated.
One really simplified model (inaccurate, but useful) of the computational state and evolution of the cell involves DNA methylation. DNA is methylated to shut it off, demethylation turns it on. To turn some DNA off or on, either DNA methyltransferase (DNMT3a/b) for methylation or one of the Tet proteins for demethylation needs to be guided to that region of DNA, usually through the assembly of some transcription factor complexes. The assembly of these complexes is combinatorial and performs logical addressing depending on the cell state. For example the cell may be expressing TF's A, B, and C, and these guide DNMT3a/b to DNA locus 3xq3945 (made up, whatever) if beta catenin translocates to the nucleus as a response to Wnt signaling, to turn something off. If TF's A, B, and D are expressed, it may bring it to a different location, and may bring Tet there instead, for demethylation.
Anyways, that's an example of "computery" description of cell biology. I don't really like how other responders shot your question down, I think the computer science mindset is really relevant to biology.
Not necessarily specifically RNA/DNA but a super accessible description of biology is The Machinery of Life (https://www.goodreads.com/book/show/6601267-the-machinery-of...). I can't get over much it makes me want to learn more, and as a lay-person, I think it gave me a much better idea of what's going on at pretty much an atomic level.
> Is there a a good read on how RNA and DNA work for a Computer Scientist?
DNA is source code. RNA is an intermediate representation. Enzymes compile DNA into mRNA. Ribosomes compile mRNA into proteins which can actually execute a wide variety of functions.
Proteins may require post-processing before they're usable. The output of a ribosome is a primary protein: a linear, one-dimensional structure. By interacting with itself and other cell machinery, the protein could be folded into three-dimensional secondary and tertiary structures. Several of them might be assembled into a quaternary protein.
The mitochondrion and the ATP synthase are like a hydroelectric power plant. The electrochemical gradient is the gravity, the hydrogen is the water and the enzyme is the turbine.
Enzymes transform substrate into product. They're like functions. When one enzyme's product is another's substrate, a pipeline is formed. Metabolism is a parallel process. I've written about metabolism as a programming metaphor before:
Sometimes bacteria save useful snippets of their own source code into gene cassettes. This allows the code to be exported to other bacteria via horizontal gene transfer.
Developed an awesome antibiotic-destroying enzyme? Make copies and send them to friends through a pipe. Didn't manage to survive? Said friends might be able to absorb the DNA from the environment anyway. They can obtain the fallen's powers just like Mega Man.
DNA is literally only instructions for building proteins (each 'gene' commonly encodes one protein). It's a very low level code, then.
The various proteins that are built are actually interacting with the environment.
So, your desire to look at interaction with the environment might be better captured by a field other than genetics: maybe proteomics or molecular biochemistry.
Maybe you can help me understand a simple example - if there is a gene that controls the eye color, how does it express itself as eye color (vs something completely different)
It's important that there isn't a gene that controls the eye colour.
Eye colour is modulated by several genes which haven't necessarily been identified - I understand this to be an open question.
I can give an example, though:
Eye colour is a function of what pigments are present in the iris, the most relevant pigment (in humans) being melanin, which also contributes to dark skin and tanning.
So, melanin is produced via the biochemical pathway 'melanogenesis'.
Among other things, the process of melanogenesis requires the enzyme tyrosinase, a protein which has a decent length wikipedia page.
If you are missing the TYR gene which codes for the protein tyrosinase, then you will likely be albino. This won't only affect your eyes, then.
I say you will 'likely' be albino only because it's hypothetically possible that a lack of tyrosinase could be compensated for with another biochemical pathway. And, of course, albinism could come about by some other break in melanin production.
A gene is like a DLL. Asking how it works would require a lot of know-how that’s specific to the usage.
When talking about how DNA is an instruction for making a protein, that protein is your data structure or a function. The next level of fundamental building block. Genes can contain a lot of information or non-information for proteins. Just like a program might have a lot of functions or data. The way they work together and interact is what creates a larger effect.
I think maybe the best starting point for understanding biology is learning about enzymes up close. They are proteins that act as “machines”. It gets down to physics and chemistry to determine how they work, so that’s probably when to drop the analogies.
Basically, the variance in melanin is what causes different eye colors. So, if you have a gene that produces melanin, and then turn it's expression down, then you might get bluer eyes.
The complicated part is that a lot of genes actually control for eye color - that is where the complications come. Each gene interacts with every other gene in a unique way.
DNA code (acgaa...) is not the only thing to be taken into account. Folding of DNA is just one more factor that influences outcome aside from raw code.
I read this as a kid: https://www.amazon.co.uk/Cartoon-Guide-Genetics/dp/006273099...
It provides a very useful bridge from a mechanistic / physic-y / computer point of view, to the more messy biochemistry. Still, whenever I think of a biochemical process, it's a cartoon from here that comes to my mind's eye.
So, from a CS point of view, I guess instead of comparing DNA to procedurally executed machine code we should be comparing it to the source code of a set of classes, which once instantiated produces specific proteins that perform all sorts of biological tasks in our bodies.
- proteins: executable object code (ribosomes are also proteins, mostly)
- epigenetics: build config options
- promoter site: `ifdef
First, imagine a system where every time you compile something, the object code is immediately launched in its own thread executing truly in parallel with all the others.
The overall behavior of the cell is the interaction of all these threads. A gene is a single block of code. They can do lots of things, including changing build options and enabling/disabling the generation of other blocks of code. We say a particular gene causes a particular effect, but really it's the aggregate interaction that does things. Most traits require the cooperation of many genes to express. If we associate a gene with a particular trait, it's usually because it is a critical component of that trait; necessary so if you break the gene the normal aggregate behavior goes away, but not sufficient - it still needs a lot of other working genes to have the right effect.
Now imagine that some of those threads run a constant cleanup process that kills running threads, delete your object code and delete files in your working directory (largely at random) while another set of threads are constantly fetching (transcriptase) and recompiling (ribosomes) code to launch new threads to keep the system working and your services up. During this process the relative number and type of running threads will change according to a combination of code and the environment.
Viruses are a tiny executable (protien coat) that copies some rogue code (RNA) into your working directory, so that constant recompilation will generate new instances that copy more code, etc.
Too many running virus instances will crash the system (kill the cell) by starving/corrupting normal processes. The random deletion and constant fetching from the repo slows the virus replication down however, and may stop it entirely.
_Retro_viruses have an additional piece:
- reverse transcriptase: 'git commit; git push'
which will copy the virus code back into your repo. Now the regular 'fetch' will copy the virus code back into your working directory.
Your immune system has processes which run around checking object hashes for threads. There's a whitelist for expected hashes (normal threads). If the same unexpected hash shows up too many times, it goes on a blacklist and you start generating antibodies- special threads that go around searching for a specific object hash and tagging that thread for deletion. If too many bad hashes are found in the same place, a white blood cell nukes the whole site from orbit.
Once you generate enough antibodies, the virus threads start getting killed before they can replicate and you're immune. If the virus mutates, the hash may not match anymore and you'll be vulnerable to the new strain. Things like the common cold and influenza mutate all the time, so you can very them over and over while chicken pox rarely mutates and youth can usually only get it once.
Vaccines are a bunch of copies of (usually inactive) threads with a particular hash, to encourage your immune system to put that hash on the blacklist.
Autoimmune diseases happen when valid code accidentally gets on the blacklist.
Cancer (a fork bomb) tends to evade the immune system because its code was already on the whitelist.
But... this is a super simplified version of how things work, and really only applies to mammals. Do not take these analogies too far.
Biology is fascinating, and definitely worth deeper study.
I remember 20 year ago, at school, when the biology teacher was presenting this dilemma. Ever since, when I hear someone saying "doing this will kill the virus", it triggers my brain into this subject, since you can't kill something if it's not alive ;)
Somewhat related, I also like the concept of the "Viruses of the Mind" [1], which makes an analogy between the spreading of a biological virus and the spreading of an ideology.
Definitely not. Viruses perform key roles in ecosystems, particularly in ocean ecosystems. Their infection and subsequent killing of organisms provides a vital mechanism for cycling nutrients. They also help keep algal blooms in check. Viruses kill 20% of bacteria in the oceans everyday.
Viruses also provide a mechanism for horizontal gene transfer. A protein that is critical to the formation of the human placenta has a viral origin.
Viruses have a massive impact on life, but we're just now starting to realize it.
The virus has no intentionality in doing them. They're a consequence of replication.
In contrast, I think a much stronger case could be made for a chimpanzee, duck, mosquito, or even amoeba evaluating multiple options, choose one to the exclusion of others, and pursueing it.
Anything can be said to have, or not have a purpose, depending on how broadly or narrowly you scope the definition.
For use in this conversation, I think it's self evident that the level of purpose exhibited by higher-complexity organisms is several orders of magnitude different than that of basic organisms.
Wasn't sure if original poster would agree / disagree.
See, I think this is exactly why you are begging the question.
The word purpose has lots of usages, but the one that seems to be discussed here is some intrinsic purpose that an object or creature has for existing.
I can perform an action with a purpose, which is different to my (personal) purpose for being alive, which is different again for some intrinsic purpose for why I am here in the first place.
It's this last purpose that daseiner1 was referring to when they asked "what’s the purpose of an amoeba? or a mosquito? or a duck? or a chimpanzee?"
They are questioning if that kind of purpose even exists.
Your argument is:
Some things have more purpose than others.
Therefore purpose exists.
In this next response you get closer to defining what purpose is - "level of purpose exhibited by higher-complexity organisms" - but we haven't really established what that purpose is or what it means to have more purpose. At best you seem to be equating complexity of behaviour to level of purpose, but I see no reason why complex behaviour should imbue some kind of purpose; all usages of the word purpose imply intent of some kind, and there are many complex processes that have no intent.
I will say that complex animals seem to be more purposeful than simple creatures, but that just means that they perform actions with more intent than simpler creatures, not that they have some intrinsic purpose themselves.
I agree there's no universal definition of purpose in this context.
I was using purpose in my sense. Daseiner1 may use the same definition, or they may be using another. As with you.
It's useless to debate anything else until we figure that out.
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My definition is contained in my original statement "reproduction without purpose is not life." I do not consider reproduction a purposeful action, as I define it.
It's hard to be intentional about something that forms the minimum bar of existence (immortal organisms aside).
I would argue that's a false dichotomy. In your terms, there can be no purpose of me without purpose of action. And purpose of action requires selection from multiple viable options.
Those two usages are not mutually exclusive, I just don't know which one you are using (or if it is some other usage).
I'm not sure that there is any intrinsic purpose to anything, only ever purpose imbued.
I understand the word gets used that way, to describe some intrinsic meaning to a life, but the word being used that way doesn't mean the thing it describes exists.
To try and be a bit clearer let me write out the three usages I am aware of and you can say which you are talking about.
1. I picked up the apple with the purpose of eating it.
2. My purpose in life is to enjoy it and leave the world a better place than when I found it.
3. The purpose of humans is to colonise the universe.
1 is purpose of an action (the action is done for a reason), 2 is purpose I give myself (I choose what gives me meaning), 3 is intrinsic purpose (regardless of what anyone wants or thinks).
It reminds me of something I read in response to that question (I can’t remember where): People love to place things in tidy categories; nature doesn’t.
Every second, we are constantly and automatically distilling insane quantities of internal and external stimuli into much simpler -- but still incredibly complex -- webs of categories, associations, and relationships. Each moment of awareness is composed entirely from these mental constructions.
We also analyze and modify our representations in various ways, both consciously and unconsciously. Science is one of the more explicit processes for doing so.
Of course, much of reality is lost and distorted in the process. But we do the best we can :) I like to think we make better maps of reality now and then.
I suppose, at the very least, some of the maps we currently possess can be used to enact more dramatic change in the world around us than ever before, which must say something about their truthiness.
I prefer the names "memetics" to talk about the field of infectious ideas and "memetic agents" when talking about single instances. A "memetic agent" is something like a virus, just replicating in minds instead of meatspace.
The SCP wiki started these terms to refer to objects which present anomalous properties when you're exposed to them, such as what the foundation regularly employs to protect articles; "memetic kill agents", basically information that kills if you consume it.
You can kill it in the sense that you stop it being a mutating replicator. That is pretty much the bare bones of life, an abstraction you can't get away from in defining life, but also one that encompasses things that aren't "life". It also applies to things like memes (both the original form from Dawkins and the internet form).
A virus is not a replicator. It is information and a transport system. The machinery of a living cell is the replicator.
It seems pretty simple to me: viruses are not living. They are able to co-opt living systems into making more of themselves.
A virus may gain life while it is inside of a cell, but why is that any different than the organic molecules which gain life when assembled into a cell? We don't say carbon is alive.
For something to be a replicator, what does that mean? Surely just that it somehow causes more of itself to be made, and has enough variability to change its descendants. A particular organic molecule like say a simple sugar doesn't fit this, because its structure is always the same. But a DNA strand can actually be any of many similar structures.
I think the distinction between what is doing the replication is spurious. The fact is even living replicators need some sort of base resource to exploit to pull off the feat. I could say that animals aren't replicators, because they inherently require other living creatures to be eaten in order to replicate.
To me, for some thing to be a replicator, that thing must include the machinery for replication. Viruses do not include that machinery. Cellular life does not include the food required to replicate, but it has the information, the machinery, and the mechanisms to gather the required resources. It is, I think, somewhat arbitrary where you draw the distinction, but it seems useful to divide replicators which do not include machinery from those that do. There are probably things which sit on this divide and make it hard to draw a distinction. That's life. It's not required to fit into our mental and linguistic bins I suppose.
So they're a parasite. There are insects that can only reproduce by laying eggs inside of another insect. They don't physically carry their own. Does that mean they're not alive?
It can be considered a collection of atoms that modifies its surroundings in a way to create similar collections of atoms.
I kind of see the point of not calling a virus a living thing. But if viruses aren't even "active" I don't really know why a cell (or even a dog) would be "active".
> Try multiplying a billion billion billion billion by a trillion trillion trillion trillion, then multiply that by a thousand, and that (10 to the 31st power) is the mind-numbing estimate of how many individual viral particles are estimated to populate the planet.
What definitions of "billion" and "trillion" are they using? 10 to the 31st would be only ten million trillion trillion, going by the common definition of million as 10 to the 6th and trillion as 10 to the 12th.
Yeah, if you multiply "a billion billion billion billion by a trillion trillion trillion trillion, then multiply that by a thousand" you get a larger number than the atoms in the observable universe.
That’s the only genesis of this error I could come up with - somehow they associated billion with 3 and trillion with 4 (conceivably because “N-illion” = 1000^(N+1) [1], and then forgot about the factor of three embedded in the base of 1000).
[1] in the US system. In Germany and historically the UK, apparently, it’s 1000,000^N = 1000^(2N), which I personally prefer.
> Try multiplying a billion by a billion, then multiply that by ten trillion, and that (10 to the 31st power) is the mind-numbing estimate of how many individual viral particles are estimated to populate the planet.
(I can't find a "correction" notice... It's Stanford Medicine, not a proper newspaper.)
Maybe Virus is akin to a SEED. Seeds are inert/dead by themselves, but it carries as all the code/DNA/instructions needed to spring to life, flourish & even reproduce infinitely when put in an friendly environment (nourished soil with water, O2 etc)
Some viruses don't directly cause the host to create new viruses. Instead they direct the creation of virus creating factories, which create the virus.
Then you get virophages which are even tinier than normal viruses, which infect the virus factories of other viruses.
Seeds are not dead. Seeds are alive because their cells are alive. If too many of the seeds cells die then the seed can no longer germinate. That's why seeds can survive long periods of frost and stay active over very long periods, it is their cells that ensure they will be able to react to changes in the environment that suggest that the seed could germinate.
What always fascinates me is that biologists talk about how these large molecules bind and self-assemble, and how enzymes control the reactions and so forth, but what are the odds? It's almost like putting the parts in the mixer, and getting your little machine in the output. I have very hard time imagining it, especially in the cell which has thousands different molecules going on inside it, how everything gets in the proper place in the end.
Firstly, evolution over billions of years makes it possible. But in more direct answer to your question about how these things self assemble - at this level atomic forces are like little magnets (I mean, literally they are the electromagnetic force) and those cause the atoms to arrange themselves in particular ways. There are lots of videos online showing this, eg. one I picked at random: https://www.youtube.com/watch?v=muNNSAYZDS8
Exactly, molecular self-assembly is completely obvious once one can see the equivalent with his own eyes.
I hope nobody complains "but he shakes the flask" -- because that is exactly what the temperature is -- how fast the particles "jiggle" as Richard Feynman would that describe:
I always thought the "flightosome" picture was a great way that biologists can demonstrate just how complex biology is.[1]
When you see a biologist draw a system in biology, say, how a protein interacts with a cell membrane and then causes a change in expression within the nucleus, it can look relatively simple.
Well, it's about as simple as drawing how an airplane works. In this example, you have the "flightosome", which is made up of fuselage, wings, cockpit and landing gear. That's what transports passengers from one airport to another.
Simple right? Well even the landing gear component is complex and with biology, we have very little understanding of it at all.
Someone who is a molecular biologist, please correct my understanding.
DNA is a molecule, made out of 4 amino acids. ACTG. There are 18 different kinds of amino acids. Amino acids are made out of carbon, nitrogen, hydrogen, oxygen. Amino acids make proteins. Proteins are the structural bricks (like LEGO) that are combined in various sequences by enzymes to build more complex machinery.
The proteins make up cell organelles, which make up cells.
How much of how DNA turns into proteins and different proteins build different structures is understood? Do we have a DNA simulator where I can write ACTG code and it tells me what kind of proteins will be made, how those proteins will interact to build complex structures?
How close are we for computer science folks to actually start writing compilers, debuggers, frameworks and simulation tools for DNA and man made cell machinery ?
How far away are we from making custom DNA + cells that act like 3D printers taking collagen and building nanometer precision complex structures?
It seems our cells already do nano manufacturing and computation, how do I tap into that ?
DNA is made of nucleic acids (deoxyribonucleic acids), not amino acids. DNA is translated to amino acids, except when it encodes long-noncoding RNAs, or miRNAs, or piRNAs, or untranslated regions, or intergenic regions, or transposons, or psuedogenes.
And the protein coding sequences are coded into proteins, except when there are alternative splicing sites, or anti-sense RNAs.
And then the protein sequence folds into their minimum free energy state, except when they are assisted by other proteins, or when they exist as disordered proteins.
And it's not always DNA -> protein. Sometimes proteins make other proteins, for example circular proteins can only be made from other proteins.
Then there are post-translational modifications, which change the RNA sequence between DNA to RNA and RNA to protein.
And then there's RNA interference, where miRNAs interfere with RNA to protein translation.
And then there's epigenetics such as DNA methlyation or histone modifications (histones are protein which compress DNA) which change what genes can be expressed when.
Really, for every rule that you've been taught, there is an exception. Biology is so much more complicated than we understand. And understanding how to make a biological computer (different from the biological computing of Adelman, yes the same Adelman as RSA) would involve understanding how all the pieces fit together.
> Do we have a DNA simulator where I can write ACTG code and it tells me what kind of proteins will be made, how those proteins will interact to build complex structures?
Without a very significant breakthrough either in computation or some biological discovery that gives a shortcut I don't think a "DNA compiler" will be available anytime soon.
I found it to be a homerun in all but addressing my 20-30 questions in these times just in the first ten minutes. To the point. Without the current yt culture of gratuitous cuts and FX.
In the case of the coronavirus, we see a significant binding affinity to the ACE2 membrane protein, which explains why the infection targets the lungs and guts so readily.
I believe it has been known for about 15 years now, that ACE2 positive epithelial cells are a potential vector for the coronavirus family of viruses.
I think with SARS-CoV-2 the pathogenesis is still not properly understood. For e.g. if you take a look at the ACE-2 expressing cell distribution, the tongue and oral cavity are very high on the list. And yet, there is no current guidance on disinfecting food before eating it, even though its a potentially high-risk route of infection.
Is this based on basic research or demographic analysis? Has the research ruled out the possibility that people who are being treated for high blood pressure are more likely to be older and in poorer shape? Because that's a pretty strong confounding effect unless the research in question is a randomized controlled trial.
I've also heard conflicting reports about Ibuprofen. I don't think anyone knows for sure.
My initial thought on Ibuprofen is just correlation not causation. How many people who get a fever will try Ibuprofen to try to lower the fever? Probably quite a few. When these people die its easy to say "well they all had Ibuprofen". That doesn't mean it had any effect.
On the flip side, NSAIDs do reduce inflammation and inflammation is part of the body's response to various stressors; I could see that lowering our response leads to worse outcomes when sick. I have always thought that cold medication increases the duration of a cold just from my own observations, so I do find it at least plausible.
I agree on the high blood pressure, if you are on it that means you have hypertension and are likely in poorer shape than someone who does not take it. I can somewhat see diuretics having an impact though as those can flush needed minerals out of your body when your body is in need. They also dehydrate you, so if you are on one and don't get properly hydrated and have a proper mineral balance, I can see that being a big negative.
Speculation surrounds ACE inhibitors (ACEI), which are a type of high blood pressure medication, in that they may dampen your immune response to viruses over long time usage. The other speculation is that circulating amounts of ACE2 are increased by ACEI and SARS-Cov-2 specifically binds to ACE2. The confounding aspects are as you suggest that the overall health including kidney health are often poorer in people with hypertension.
From what I remember it’s the opposite. They target the ACE receptors inhibiting them and for this reason they make the ACE2 receptors more sensible facilitating the virus infection.
Looks like it hasn't been posted yet. This article came out today, this is the most recent article from that author, and google didn't turn up anything. It's strange how the end implies that part 2 already exists though.
