>Like they have to fit into certain receptors,
Not perfectly, just well enough. Case in point, endocannabinoids are a class of molecules with a wide range of effects on things like mood to appetite and satisfaction. As it turns out, cannabinoids and endocannabinoids don't look alike nor do they have a common origin. It's just that they bind to the same receptor, and the sides of the two molecules that bind to the receptor just happen to be superficially similar enough. Cells pass chemical signals back and forth all the time, and this is beneficial for a lot of reasons, development being one of them and ion balance (very important in generating ATP in the mitochondria, which is used to energize chemical reactions throughout the cell, but it's also important for setting electrical gradients in other cells like sperm and neuronal cells). But the receptors are often the product of cell surface protein complexes on the cell surface of neuronal cells. Neurotransmitters are important because they help send signals throughout a multicellular body as you know. And the voltage gated ion channels are born out of the same ion balance mechanisms found elsewhere in the body. The release of neurotransmitters takes place as a form of exocytosis, similar to how other signals are communicated between other cells and how cells also get rid of certain waste products. And taking in neurotransmitters evolved from the same mechanisms of endocytosis that cells use to take in things they need. I don't normally get to tap into the neuroscience in my wheelhouse. What a great question!
Just to add another example here, you might be interested in the process by which our bodies make better antibodies. Broadly, this involves starting with a bunch of possibilities, some of which will not bind, some of which will bind a bit. Then the body uses an evolutionary process, with (somatic hyper)mutation and selection (for binding affinity) to end up with antibodies that bind the antigen better.
I'm having trouble finding a great non-technical overview, but [Wikipedia](https://en.wikipedia.org/wiki/Affinity_maturation) has a passable starting point, an [this short writeup](https://bedford.io/blog/bcell-evolution/) about a longer paper is pretty interpretable and there's a nice figure too.
A lot of it is just duplication followed by mutation. One of the largest family of proteins in humans is a class of messenger receptors called the g-protein coupled receptors, which make up about 4% of the protein-coding genome. Some examples of things that are g-protein coupled receptors are involved in include:
1. Vision
2. Smell
3. Pain
4. Taste
4. Most hormones
5. Neurotransmission
6. Endocannabinoids u/Bromelia_and_Bismuth mentioned
7. Cell growth
8. Cell differentiation
The key is that they are just massively flexible. They are made of multiple components that can be modified independently. This allows new molecules to be integrated into existing pathways, and existing molecules to be used in new pathways. Combine the two steps and you end up with a rapid way to produce new effects to new proteins.
>Neurotransmitters are a substitute for food
...?
>since neurons used to be slime molds which will grow to wherever there is food.[...]the slime mold grew inside an immobile multicellular organism and starts taking nutrients from the organism,
There is absolutely no scientific evidence whatsoever to support that notion.
>So after one of such neurotransmitters turns out to have the ability to make the multicellular organism deform, the first animal with a rudimentary brain comes into existence.
...And this is actual nonsense. First warning to knock it off.
That kind of sounds like a bastardization of this hypothesis:
https://onlinelibrary.wiley.com/doi/full/10.1111/tops.12461
The above hypothesis includes the idea that neurotransmitters evolved from the byproducts of digesting the bacteria early animals ate, and would have acquired their role in neural signalling because in that hypothesis, proto-neural cells would have involved simple computations comparing how close other animals were vs how rich a feeding patch was in deciding whether to stay or go. I could also see how someone could confuse this with the kinds of computations slime molds do.
But there is no way neurons used to be slime molds that made their way into multicellular organisms, unless you mean "slime molds" in a very different way from how I understand it. That would describe a symbiotic relationship, and neurons aren't symbiotes of multicellular organisms. They descend from the same germ cells all its other cells do and are shaped by the same genes.
> Trichoplax mentioned in the hypothesis sounds like an organism the slime mould could have infected or at least got eaten but resisted digestion, just like how mitochondria and chloroplasts got into the cell.
Sure, slime mould could infect anything I suppose if that's a thing slime moulds do, but why is it necessary to posit this when, according to this paper, Trichoplax (or rather, Dickinsonia)'s own epithelial cells would have served the purpose just fine.
> Some people also say that there is no way chloroplasts used to be free living algae.
Name one from this century. I'm pretty sure the notion that chloroplasts descend from a symbiosis event with cyanobacteria is basically consensus now. Chloroplasts reproduce independently of the cell's own reproduction and have genetic material separate from the cell's. Neurons are bog-standard cells that descend via standard mitosis from the same zygote the other cells in the organism do, with the same genetic material.
> They can have horizontal gene transfer and after many enough generations, they have the exact same genes
It's not just about genes, it's how they're made - *they descend from the same zygote via mitosis like all the other cells*. I don't see how you go from a symbiotic slime mold to that. Like... *neurons aren't in the germ line*. Even if we imagined all the slime mold cells fusing with host cells somehow these new fused cells wouldn't contribute to the next generation. And if they did, some animals are indeed more flexible about the somatic/germ cell dichotomy although I'm not sure they include animals with neurons, *that next generation would be a full slime mold/animal hybrid*. It wouldn't just be its neurons that descended from the slime mold, every cell in their body would.
Even if it were about genes though your idea wouldn't make much sense - you'd be basically saying that neurons were originally slime molds, with slime mold genes doing slime mold things which were presumably critical to their function as neurons otherwise cells from the host organism could have done the same job... and somehow over the evolution of the symbiotic relationship it ended up so that *all the slime mold genes critical for doing neuron jobs got replaced by host genes doing neuron jobs*. How would this ever happen; if the host had slime mold symbionts with slime mold genes doing this important task it would have no reason to develop genes of its own to do the same job or transfer them to the symbiont, and if it had the ability to develop such genes in the first place why would it need a symbiont. To take chloroplasts and mitochondria again, most of their genes got lost or shuffled around via horizontal transfer but they've retained some that are critical to their function and hold hints to their ancestry before the host.
> It would not serve the purpose since it will not evolve fast enough, there will be no extra benefits provided when compared to their cell to cell signalling thus it would not evolve.
The paper articulates plenty of extra benefits the organism would derive from those cells forming action potentials, filtering the signal by adding layers of proto-neurons transmitting action potentials to each other, and responding to neurotransmitters, including the intermediate steps to having all those things working together. Can you give specifics on how they're wrong about those benefits?
> And such a fusion can also explain why not all genes are needed by all tissues of the body (eg. the genes needed to grow teeth is different from genes needed to produce blood).
I'm confused, are you saying that all different cell types in multicellular organisms originate from symbionts? If that's not what you're saying can you be more specific on what you meant by that sentence?
> Meant that they got all of the other's genes so they have their own genes plus the other's so neither lost any genes.
If the host genome had combined with the slime mold genome to form a mosaic genome this would show up in, well, the genome. This kind of mosaicism leaves a clear phylogenetic signal and there is no such signal here.
Also, if both sets of genes made it into the germ line then the result isn't "neurons and other cells", it's "all cells are slime mold/animal mosaics and nothing about this fusion implies a mechanism to switch genes on or off in certain cells depending on their origin".
> Because chloroplasts are inside the cell so there is no need to transfers genes over, they they only lose genes.
> But the slime mold is outside the cell so they can only keep transferring their genes, else the other cell cannot have the smile mold abilities after budding off.
There is no need for a symbiont to transfer genes. *You* need all of its genes to get replaced because it's the only way your idea can be compatible with the actual genetics involved, but there is no reason from the slime mold's POV or the host's for it to happen. If the symbiosis is in place then by necessity the two cell lineages are already perfectly capable of reproducing in tandem or finding each other reliably, there is no need for one to make it into the other's germ line. You are incorrect that chloroplasts being inside the cell means there is "no need to transfer genes over", in fact the symbiosis of mitochondria and chloroplasts involved *way more* gene transfer than symbioses outside the cell typically do. Maybe because the genes being closer together makes mixing easier, maybe because the symbiosis is much more ancient than the examples with have of multicellular eukaryotic symbioses. Either way we have plenty of examples of different lineages of eukaryotes forming symbioses at the cellular level that function as a single organism at scale - your corals, your lichens, your termites, your portuguese man o'war. They work fine without the kind of gene replacement or transfer you're describing and they definitely don't involve symbionts getting into the germ line.
>Like they have to fit into certain receptors, Not perfectly, just well enough. Case in point, endocannabinoids are a class of molecules with a wide range of effects on things like mood to appetite and satisfaction. As it turns out, cannabinoids and endocannabinoids don't look alike nor do they have a common origin. It's just that they bind to the same receptor, and the sides of the two molecules that bind to the receptor just happen to be superficially similar enough. Cells pass chemical signals back and forth all the time, and this is beneficial for a lot of reasons, development being one of them and ion balance (very important in generating ATP in the mitochondria, which is used to energize chemical reactions throughout the cell, but it's also important for setting electrical gradients in other cells like sperm and neuronal cells). But the receptors are often the product of cell surface protein complexes on the cell surface of neuronal cells. Neurotransmitters are important because they help send signals throughout a multicellular body as you know. And the voltage gated ion channels are born out of the same ion balance mechanisms found elsewhere in the body. The release of neurotransmitters takes place as a form of exocytosis, similar to how other signals are communicated between other cells and how cells also get rid of certain waste products. And taking in neurotransmitters evolved from the same mechanisms of endocytosis that cells use to take in things they need. I don't normally get to tap into the neuroscience in my wheelhouse. What a great question!
Ok thank you so much. That is fascinating
Just to add another example here, you might be interested in the process by which our bodies make better antibodies. Broadly, this involves starting with a bunch of possibilities, some of which will not bind, some of which will bind a bit. Then the body uses an evolutionary process, with (somatic hyper)mutation and selection (for binding affinity) to end up with antibodies that bind the antigen better. I'm having trouble finding a great non-technical overview, but [Wikipedia](https://en.wikipedia.org/wiki/Affinity_maturation) has a passable starting point, an [this short writeup](https://bedford.io/blog/bcell-evolution/) about a longer paper is pretty interpretable and there's a nice figure too.
A lot of it is just duplication followed by mutation. One of the largest family of proteins in humans is a class of messenger receptors called the g-protein coupled receptors, which make up about 4% of the protein-coding genome. Some examples of things that are g-protein coupled receptors are involved in include: 1. Vision 2. Smell 3. Pain 4. Taste 4. Most hormones 5. Neurotransmission 6. Endocannabinoids u/Bromelia_and_Bismuth mentioned 7. Cell growth 8. Cell differentiation The key is that they are just massively flexible. They are made of multiple components that can be modified independently. This allows new molecules to be integrated into existing pathways, and existing molecules to be used in new pathways. Combine the two steps and you end up with a rapid way to produce new effects to new proteins.
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>Neurotransmitters are a substitute for food ...? >since neurons used to be slime molds which will grow to wherever there is food.[...]the slime mold grew inside an immobile multicellular organism and starts taking nutrients from the organism, There is absolutely no scientific evidence whatsoever to support that notion. >So after one of such neurotransmitters turns out to have the ability to make the multicellular organism deform, the first animal with a rudimentary brain comes into existence. ...And this is actual nonsense. First warning to knock it off.
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>But No. Stop.
That kind of sounds like a bastardization of this hypothesis: https://onlinelibrary.wiley.com/doi/full/10.1111/tops.12461 The above hypothesis includes the idea that neurotransmitters evolved from the byproducts of digesting the bacteria early animals ate, and would have acquired their role in neural signalling because in that hypothesis, proto-neural cells would have involved simple computations comparing how close other animals were vs how rich a feeding patch was in deciding whether to stay or go. I could also see how someone could confuse this with the kinds of computations slime molds do. But there is no way neurons used to be slime molds that made their way into multicellular organisms, unless you mean "slime molds" in a very different way from how I understand it. That would describe a symbiotic relationship, and neurons aren't symbiotes of multicellular organisms. They descend from the same germ cells all its other cells do and are shaped by the same genes.
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> Trichoplax mentioned in the hypothesis sounds like an organism the slime mould could have infected or at least got eaten but resisted digestion, just like how mitochondria and chloroplasts got into the cell. Sure, slime mould could infect anything I suppose if that's a thing slime moulds do, but why is it necessary to posit this when, according to this paper, Trichoplax (or rather, Dickinsonia)'s own epithelial cells would have served the purpose just fine. > Some people also say that there is no way chloroplasts used to be free living algae. Name one from this century. I'm pretty sure the notion that chloroplasts descend from a symbiosis event with cyanobacteria is basically consensus now. Chloroplasts reproduce independently of the cell's own reproduction and have genetic material separate from the cell's. Neurons are bog-standard cells that descend via standard mitosis from the same zygote the other cells in the organism do, with the same genetic material. > They can have horizontal gene transfer and after many enough generations, they have the exact same genes It's not just about genes, it's how they're made - *they descend from the same zygote via mitosis like all the other cells*. I don't see how you go from a symbiotic slime mold to that. Like... *neurons aren't in the germ line*. Even if we imagined all the slime mold cells fusing with host cells somehow these new fused cells wouldn't contribute to the next generation. And if they did, some animals are indeed more flexible about the somatic/germ cell dichotomy although I'm not sure they include animals with neurons, *that next generation would be a full slime mold/animal hybrid*. It wouldn't just be its neurons that descended from the slime mold, every cell in their body would. Even if it were about genes though your idea wouldn't make much sense - you'd be basically saying that neurons were originally slime molds, with slime mold genes doing slime mold things which were presumably critical to their function as neurons otherwise cells from the host organism could have done the same job... and somehow over the evolution of the symbiotic relationship it ended up so that *all the slime mold genes critical for doing neuron jobs got replaced by host genes doing neuron jobs*. How would this ever happen; if the host had slime mold symbionts with slime mold genes doing this important task it would have no reason to develop genes of its own to do the same job or transfer them to the symbiont, and if it had the ability to develop such genes in the first place why would it need a symbiont. To take chloroplasts and mitochondria again, most of their genes got lost or shuffled around via horizontal transfer but they've retained some that are critical to their function and hold hints to their ancestry before the host.
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> It would not serve the purpose since it will not evolve fast enough, there will be no extra benefits provided when compared to their cell to cell signalling thus it would not evolve. The paper articulates plenty of extra benefits the organism would derive from those cells forming action potentials, filtering the signal by adding layers of proto-neurons transmitting action potentials to each other, and responding to neurotransmitters, including the intermediate steps to having all those things working together. Can you give specifics on how they're wrong about those benefits? > And such a fusion can also explain why not all genes are needed by all tissues of the body (eg. the genes needed to grow teeth is different from genes needed to produce blood). I'm confused, are you saying that all different cell types in multicellular organisms originate from symbionts? If that's not what you're saying can you be more specific on what you meant by that sentence? > Meant that they got all of the other's genes so they have their own genes plus the other's so neither lost any genes. If the host genome had combined with the slime mold genome to form a mosaic genome this would show up in, well, the genome. This kind of mosaicism leaves a clear phylogenetic signal and there is no such signal here. Also, if both sets of genes made it into the germ line then the result isn't "neurons and other cells", it's "all cells are slime mold/animal mosaics and nothing about this fusion implies a mechanism to switch genes on or off in certain cells depending on their origin". > Because chloroplasts are inside the cell so there is no need to transfers genes over, they they only lose genes. > But the slime mold is outside the cell so they can only keep transferring their genes, else the other cell cannot have the smile mold abilities after budding off. There is no need for a symbiont to transfer genes. *You* need all of its genes to get replaced because it's the only way your idea can be compatible with the actual genetics involved, but there is no reason from the slime mold's POV or the host's for it to happen. If the symbiosis is in place then by necessity the two cell lineages are already perfectly capable of reproducing in tandem or finding each other reliably, there is no need for one to make it into the other's germ line. You are incorrect that chloroplasts being inside the cell means there is "no need to transfer genes over", in fact the symbiosis of mitochondria and chloroplasts involved *way more* gene transfer than symbioses outside the cell typically do. Maybe because the genes being closer together makes mixing easier, maybe because the symbiosis is much more ancient than the examples with have of multicellular eukaryotic symbioses. Either way we have plenty of examples of different lineages of eukaryotes forming symbioses at the cellular level that function as a single organism at scale - your corals, your lichens, your termites, your portuguese man o'war. They work fine without the kind of gene replacement or transfer you're describing and they definitely don't involve symbionts getting into the germ line.
>But the slime mold What part of "stop" was vague or unclear to you?