4 ms·

Yes in mice but this is startling to me that you can just drop a random protein from one species and have it work in another. Whatever weird programming languag

Yes in mice but this is startling to me that you can just drop a random protein from one species and have it work in another. Whatever weird programming language life is made from it seems to be a surprisingly forgiving environment. I wonder if the leap between a fish and a mouse is less than the distance between a mouse and a human? And no I doubt this will suddenly work in humans I’m more just fascinated by genetics proteins and life in general and just constantly amazed any of this works at all.

PittleyDunkin 2y ago
> Whatever weird programming language life is made from it seems to be a surprisingly forgiving environment. Either that, or we truly are more similar than we seem to ourselves. It makes sense that humans would have a greater sense of discernment at the sensual level genetically nearer to us than further from us.
- idiotsecant 2y ago
  I mean, quantitatively we are quite similar, when it comes down to the total possibility space dna allows, all life on earth is practically identical, statistically
BurningFrog 2y ago
I assume we only hear about the cases when the protein does something interesting, and not the 999/1000 cases when it doesn't.
jaggederest 2y ago
It's all just chemistry, and the chemistry is extremely conservative all the way back to the first eukaryotes. Once our kind of life figures out a way to do something it's very uncommon that the fundamental pathways change - not by any means impossible. Cells that have novel things happen to them nearly always die. Others become cancer, which is a career-limiting move for multicellular life at least. So the process of changes to basic chemistry of life is very slow. That's why omnivores can eat almost anything and be fine with it - imagine if different branches of plants and animals had really novel things in them, like a critter with nerve gas for a circulatory fluid. There's been some discussion of mirror bacteria lately, which have opposite chirality in all their molecules, which would be substantially problematic since we really don't have defenses against that kind of thing. That just shows the degree to which you'd have to rejigger biochemistry to get a truly whole new thing going on.
- Eddy_Viscosity2 2y ago
  Like all plants that produce sugar produce left-handed sugar molecules. And all animals that can digest sugar can only digest left-handed sugar molecules. There was no meeting, this is just the way it worked out.
  - KyleSanderson 2y ago
    The meeting was the animals who evolved to not be able to consume this, lived in more harsh conditions than those that had the readily available sugar. Evolution.
    - malux85 2y ago
      Yeah, having the reward function baked into the runtime is a sure way to eliminate any nonsense!
  - alphan0n 2y ago
    Our physiology can still interact with other chiral molecules though right? Just for example, both the stereoisomers, dextro/levo amphetamine, in my limited understanding of pharmacological interactions, cause a reaction. One being a powerful stimulant/psychotropic that can cause psychosis, the other benign enough to be sold over the counter as a nasal decongestant with stimulating effects, but orders of magnitude weaker.
    - throwup238 2y ago
      You are correct. Protein chirality determines which direction they twist when they fold but the binding sites are all made up of the same functional groups, just arranged differently. Realistically they have to be compatible because chirality is enforced by a D-handed chiral checkpoint protein that preferentially binds to L-amino acids, excluding the D-amino acids. All living organisms use the “wrong” isomer to make sure only the “right” isomer is used in protein synthesis. The amino acid cysteine is also present in both forms in mammals, so it extends to small molecules too.
    - 2y ago
clort 2y ago
> I wonder if the leap between a fish and a mouse is less than the distance between a mouse and a human? No, mice are mammals just like humans. Fish were around long before mammals even existed.
- vhcr 2y ago
  Under a monophyletic definition, mammals are fish.
  - deleted 2y ago
    [deleted]
  - ajuc 2y ago
    Tuna is closer related to humans than to sharks for one example. So if your definition of fish contains tuna and sharks - it also has to contain homo sapiens and whales.
- Almondsetat 2y ago
  genetic distance and taxonomical distance aren't that correlated
  - dekhn 2y ago
    This is mainly due to errors in the taxonomy being based on phenotypic similarity which often does not correlate with actual relatedness (although, many would argue with this statement). It's not uncommon to see taxonomic reclassifications after enough species are sequenced.
kleton 2y ago
It is a protein that exists in mammals. Presumably they produced the murine version to put in the mouse. Science journalism screwed up the paper's language, calling it a zebrafish protein, when it is a protein that is conserved for all vertebrates. But the function of the protein, and its role in heart regeneration, was identified in zebrafish. > Directly after LAD ligation during MI surgery, hearts were injected twice with 15 μl of AAV9(CMV:GFP) or AAV9(CMV:HA-Hmga1) (1 × 1012 virus particles per mouse) in opposing regions bordering the area at risk of ischemic injury. The paper doesn't say whether the viral vector (AAV9) used the murine or zebrafish Hmga1 sequence, but it is more likely that they used the murine.
est31 2y ago
Babies can heal from heart damage really well, the ability is lost in your life's first few months. So this is just turning on a flag.
- ajuc 2y ago
  There's probably a reason it turns off. Cancer chance?
metalman 2y ago
one of the earliest and my personal favorite chymeric animals, were bioluminesent jellyfish monkeys, 2001 or before. The only one to glow visibly in normal light didnt live long, but some of the rest, that only glowed under infrared/black lights, did ok. So the zebrafish thing just might work. Also done by some mad scientist experimenting on themselves, was the injection, into there eyes of a chemical produced by deap sea ?squid I think that humans dont produce any apreciable amount of, but we have the receptors for, and gives supper enhanced night vision to humans who are mad enough to give it a go.
- Modified3019 2y ago
  Ah, are you talking about Chlorin e6? I’m not sure if it’s squid inspired. https://www.sciencealert.com/scientists-have-figured-out-how-to-inject-human-eyes-with-night-vision https://www.sciencealert.com/scientists-have-figured-out-how...
dekhn 2y ago
Well it's important to note that all organisms (almost certainly) descend from a single common ancestor (https://en.wikipedia.org/wiki/Last_universal_common_ancestor https://en.wikipedia.org/wiki/Last_universal_common_ancestor) and the organisms we work with often are quite close on the inheritance tree (really, a graph if you include horizontal gene transfer). When you collect the same exact protein from a bunch of close species, their underlying sequences often differ by very little and those differences are really just random mutations that occurred and were tolerated. Some proteins got "locked in" as useful and could not really change since so many things depended on them. For example, eukaryotes like humans have a protein called "actin" that is incredibly well consereved across all mammals, and we can even see what appear to be very distant cousins in bacteria- those two parts of the tree of life diverged billions of years ago (you think legacy computing is bad?) If you start to study biology through the lens of evolution/development (IE, looking at the similarities and differences in close and far related organisms) it starts to become a lot clearer. Many organisms with very different phenotypes actually just contain slight modifications to the parameters of common generator functions- for example, wings and arms seem to derive from the same ancestral body part. Most of the genes that make them are in common, it's just how and when the different genes get expressed that determines the finer details (I'm glossing over a lot here). So since nearly all the players are the same, it's often not that hard to move a protein from a close relative (mice are pretty close to us) to another without any real loss of function or major change in phenotype. However, there are some fundamental differences that make comparing mice results to humans and sometimes we modify mice to appear more human to make them better model organisms. (even after working in this field for some 30+ years, I remain constantly amazed any of this works at all. I felt the same way about Google's production environment, which in many ways resembled a very simple organism)
- mncharity 2y ago
  > If you start to study biology through the lens of evolution/development (IE, looking at the similarities and differences in close and far related organisms) it starts to become a lot clearer. Any suggestions on literature? Paper, survey article, text, whatever? Or any examples/thoughts of using that as a pedagogical framework? I've an oddball interest in exploring what science education content might look like if crafted with far far greater interdisciplinary expertise and resources. So I've wondered what an intro bio might look like with a more... "veterinary + engineering" flavor - broad scope, comparative and cross-cutting, systems concerns, solution vocabularies, etc. As an illustrative bit (years old so maybe now invalidated), perhaps highly-conserved regulatory micro-RNA might be used as a "available complexity" metric to create a much simpler "tree of life" for orientation. Or energy budgets as a lens. Or design themes (eg compartmentalization). Or conserved-outward (eg 16S to RNA to). Or emotive ("yay diffusion, and surfing just above the thermal-noise molecular mosh pit from hell" vs (an Analog Devices engineer's heartfelt) "Brownian motion is the devil. The DEVIL!!"). Or someone's picture book of motifs in cellular and embryonic development (eg perching pigeons spacing themselves evenly along a wire). Or ... . Most everyone is quite reasonably focused on the students and resources and objectives at hand. But that leaves the heavy lifting of exploring for long-term transformative opportunities rather unincentivized. Making it hard to envision just how much potential is being left on the table.
dkkergoog 2y ago
[dead]

PittleyDunkin 2y ago

> Whatever weird programming language life is made from it seems to be a surprisingly forgiving environment. Either that, or we truly are more similar than we seem to ourselves. It makes sense that humans would have a greater sense of discernment at the sensual level genetically nearer to us than further from us.

idiotsecant 2y ago
I mean, quantitatively we are quite similar, when it comes down to the total possibility space dna allows, all life on earth is practically identical, statistically

BurningFrog 2y ago

I assume we only hear about the cases when the protein does something interesting, and not the 999/1000 cases when it doesn't.

jaggederest 2y ago

It's all just chemistry, and the chemistry is extremely conservative all the way back to the first eukaryotes. Once our kind of life figures out a way to do something it's very uncommon that the fundamental pathways change - not by any means impossible. Cells that have novel things happen to them nearly always die. Others become cancer, which is a career-limiting move for multicellular life at least. So the process of changes to basic chemistry of life is very slow. That's why omnivores can eat almost anything and be fine with it - imagine if different branches of plants and animals had really novel things in them, like a critter with nerve gas for a circulatory fluid. There's been some discussion of mirror bacteria lately, which have opposite chirality in all their molecules, which would be substantially problematic since we really don't have defenses against that kind of thing. That just shows the degree to which you'd have to rejigger biochemistry to get a truly whole new thing going on.

Eddy_Viscosity2 2y ago
Like all plants that produce sugar produce left-handed sugar molecules. And all animals that can digest sugar can only digest left-handed sugar molecules. There was no meeting, this is just the way it worked out.
- KyleSanderson 2y ago
  The meeting was the animals who evolved to not be able to consume this, lived in more harsh conditions than those that had the readily available sugar. Evolution.
  - malux85 2y ago
    Yeah, having the reward function baked into the runtime is a sure way to eliminate any nonsense!
- alphan0n 2y ago
  Our physiology can still interact with other chiral molecules though right? Just for example, both the stereoisomers, dextro/levo amphetamine, in my limited understanding of pharmacological interactions, cause a reaction. One being a powerful stimulant/psychotropic that can cause psychosis, the other benign enough to be sold over the counter as a nasal decongestant with stimulating effects, but orders of magnitude weaker.
  - throwup238 2y ago
    You are correct. Protein chirality determines which direction they twist when they fold but the binding sites are all made up of the same functional groups, just arranged differently. Realistically they have to be compatible because chirality is enforced by a D-handed chiral checkpoint protein that preferentially binds to L-amino acids, excluding the D-amino acids. All living organisms use the “wrong” isomer to make sure only the “right” isomer is used in protein synthesis. The amino acid cysteine is also present in both forms in mammals, so it extends to small molecules too.
  - 2y ago

clort 2y ago

> I wonder if the leap between a fish and a mouse is less than the distance between a mouse and a human? No, mice are mammals just like humans. Fish were around long before mammals even existed.

vhcr 2y ago
Under a monophyletic definition, mammals are fish.
- deleted 2y ago
  [deleted]
- ajuc 2y ago
  Tuna is closer related to humans than to sharks for one example. So if your definition of fish contains tuna and sharks - it also has to contain homo sapiens and whales.
Almondsetat 2y ago
genetic distance and taxonomical distance aren't that correlated
- dekhn 2y ago
  This is mainly due to errors in the taxonomy being based on phenotypic similarity which often does not correlate with actual relatedness (although, many would argue with this statement). It's not uncommon to see taxonomic reclassifications after enough species are sequenced.

kleton 2y ago

It is a protein that exists in mammals. Presumably they produced the murine version to put in the mouse. Science journalism screwed up the paper's language, calling it a zebrafish protein, when it is a protein that is conserved for all vertebrates. But the function of the protein, and its role in heart regeneration, was identified in zebrafish. > Directly after LAD ligation during MI surgery, hearts were injected twice with 15 μl of AAV9(CMV:GFP) or AAV9(CMV:HA-Hmga1) (1 × 1012 virus particles per mouse) in opposing regions bordering the area at risk of ischemic injury. The paper doesn't say whether the viral vector (AAV9) used the murine or zebrafish Hmga1 sequence, but it is more likely that they used the murine.

est31 2y ago

Babies can heal from heart damage really well, the ability is lost in your life's first few months. So this is just turning on a flag.

ajuc 2y ago
There's probably a reason it turns off. Cancer chance?

metalman 2y ago

one of the earliest and my personal favorite chymeric animals, were bioluminesent jellyfish monkeys, 2001 or before. The only one to glow visibly in normal light didnt live long, but some of the rest, that only glowed under infrared/black lights, did ok. So the zebrafish thing just might work. Also done by some mad scientist experimenting on themselves, was the injection, into there eyes of a chemical produced by deap sea ?squid I think that humans dont produce any apreciable amount of, but we have the receptors for, and gives supper enhanced night vision to humans who are mad enough to give it a go.

Modified3019 2y ago
Ah, are you talking about Chlorin e6? I’m not sure if it’s squid inspired. https://www.sciencealert.com/scientists-have-figured-out-how-to-inject-human-eyes-with-night-vision https://www.sciencealert.com/scientists-have-figured-out-how...

dekhn 2y ago

Well it's important to note that all organisms (almost certainly) descend from a single common ancestor (https://en.wikipedia.org/wiki/Last_universal_common_ancestor https://en.wikipedia.org/wiki/Last_universal_common_ancestor) and the organisms we work with often are quite close on the inheritance tree (really, a graph if you include horizontal gene transfer). When you collect the same exact protein from a bunch of close species, their underlying sequences often differ by very little and those differences are really just random mutations that occurred and were tolerated. Some proteins got "locked in" as useful and could not really change since so many things depended on them. For example, eukaryotes like humans have a protein called "actin" that is incredibly well consereved across all mammals, and we can even see what appear to be very distant cousins in bacteria- those two parts of the tree of life diverged billions of years ago (you think legacy computing is bad?) If you start to study biology through the lens of evolution/development (IE, looking at the similarities and differences in close and far related organisms) it starts to become a lot clearer. Many organisms with very different phenotypes actually just contain slight modifications to the parameters of common generator functions- for example, wings and arms seem to derive from the same ancestral body part. Most of the genes that make them are in common, it's just how and when the different genes get expressed that determines the finer details (I'm glossing over a lot here). So since nearly all the players are the same, it's often not that hard to move a protein from a close relative (mice are pretty close to us) to another without any real loss of function or major change in phenotype. However, there are some fundamental differences that make comparing mice results to humans and sometimes we modify mice to appear more human to make them better model organisms. (even after working in this field for some 30+ years, I remain constantly amazed any of this works at all. I felt the same way about Google's production environment, which in many ways resembled a very simple organism)

mncharity 2y ago
> If you start to study biology through the lens of evolution/development (IE, looking at the similarities and differences in close and far related organisms) it starts to become a lot clearer. Any suggestions on literature? Paper, survey article, text, whatever? Or any examples/thoughts of using that as a pedagogical framework? I've an oddball interest in exploring what science education content might look like if crafted with far far greater interdisciplinary expertise and resources. So I've wondered what an intro bio might look like with a more... "veterinary + engineering" flavor - broad scope, comparative and cross-cutting, systems concerns, solution vocabularies, etc. As an illustrative bit (years old so maybe now invalidated), perhaps highly-conserved regulatory micro-RNA might be used as a "available complexity" metric to create a much simpler "tree of life" for orientation. Or energy budgets as a lens. Or design themes (eg compartmentalization). Or conserved-outward (eg 16S to RNA to). Or emotive ("yay diffusion, and surfing just above the thermal-noise molecular mosh pit from hell" vs (an Analog Devices engineer's heartfelt) "Brownian motion is the devil. The DEVIL!!"). Or someone's picture book of motifs in cellular and embryonic development (eg perching pigeons spacing themselves evenly along a wire). Or ... . Most everyone is quite reasonably focused on the students and resources and objectives at hand. But that leaves the heavy lifting of exploring for long-term transformative opportunities rather unincentivized. Making it hard to envision just how much potential is being left on the table.

dkkergoog 2y ago

[dead]