The RETSAT gene, previously studied only for its role in fat storage, contains a missense mutation at position 247 (Q247R) that changes the amino acid sequence and alters the protein's structure. This mutation is a gain-of-function change found convergently across multiple high-altitude species, including yaks, Tibetan antelopes, and reportedly snow leopards, suggesting it helps these animals maintain white matter and nerve insulation under chronic low-oxygen stress. The hosts frame this cross-species conservation as the signal that pointed researchers toward RETSAT as a candidate mechanism worth investigating for its potential relevance to myelin repair in diseases like multiple sclerosis.
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The hosts compare this evolutionary approach to how Gila monster venom led to Ozempic, framing animal adaptation as a proven route to human therapeutics.
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The research team is described as coming from several Chinese universities with a lead author based in Shanghai, giving them regional proximity to Tibetan Plateau species.
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The hosts mention China has a broader effort to sequence genomes of its exotic animals, which they suggest may have supported this discovery.
746 words · auto-generated from the episode video
54:12Gaiaong University. It's a bunch of researchers that have published in Neuron that show that the genomes of these creatures has a amino acid change in a gene called retat which is retinol saturates. We're going to get into what exactly that is, but that mutation in that gene is a gain of function mutation. But in this case, the gain of function is a natural gain of function that is caused by evolutionary mechanisms to let yaks and snow leopards and all of these animals survive in that hypoxic environment. The key thing is
54:54this is across animals. >> This is conserved. This single mutation is conserved not just in the axe, it's in the Tibetan antelope. >> It's multiple which means that there is something there. >> Yeah. It is the the substrate is has some universality to it. >> Yeah. >> Not the substrate but there's a fundamental that has universality to it. >> Exactly. And it's a missense mutation meaning it's not a mutation where the amino acid is unchanged. This is a different amino acid that has gone into the protein. So it has changed the structure of this protein that is coming from the gene, right? So there's something that is going on and historically this gene I mean it's been studied before because we study genes
55:35all the time. This retinol saturates it's just been studied for the context of fat storage. >> That's been it. >> Mhm. >> Now there could be something else, right? Because now all of a sudden we found a mutation that is very specific to species that live in hypoxia. >> Mhm. It's been found in yaks. It's been found in Tibetan antelopes, possibly others. So, this convergent evolution, that signal is what told these researchers that there might be something going on. >> And so, just to set the table one more time, we've identified why in multiple sclerosis like functionally what's happening. >> Mhm. All the research demilination
56:18>> all the research that led to this place of we know how we need to deliver to the source to solve the problem but we've been unable to solve the problem because we can't target the therapeutic enough to not degrade other systems >> in a separate lane from that setup. >> Yeah. Uh this idea of um studying the evolution across other animals on planet Earth has actually led to therapeutic solutions in humans in other use cases. The famous one we talked about being ompic where we looked at Gila Monster Venom. >> Yeah. >> Uh and its ability to basically make
56:59allow you to survive with less blood sugar which is great if you want to manage >> diabetes. diabetes, type two or obesity >> or obesity. And so the methodology of looking at other evolutionary examples to solve problems in humans >> has been wildly successful already. >> Yeah. >> And in this environment, it's notable that this is coming out of uh several Chinese universities. >> Yeah. >> Who have a proximity >> the main author is from Shanghai, but yeah. >> Uh you know across it's a big team. >> Um who have proximity to Tibet. >> Yep. Um, so it's a context where they they'll have, you know, regional reference points for this. >> And there's, I think, I think there's
57:39also a a government sort of effort to >> get the genomes of all of its exotic animals, >> which makes sense in China, which makes sense totally >> because of exactly what we're talking about. Who knows what benefits come out of having the information? And so they've now found that in these uh low oxygen environments, a variety of of species have been able to find a way to live. >> Yeah. >> Um >> and specifically combat white matter degradation, >> which is related to this the problem with MS. >> And so we're trying to see is there a bridge
58:19>> now between these two things. Lego blocks >> and we're going to try to see if we can build a bridge between the researchers said, okay, we've got this substitution at the 247 locus and this is a gain of function mutation because clearly this thing is doing well, right? Um, this thing is causing the individuals, the species to actually create white matter even under environmental stress, even under the stress of low oxygen. First of all, how
Evolutionary BiologyNeurobiologyPharmacologyRegenerative Medicine