4 ms·

I hope someone works on recovering UOX (Urate Oxidase)[1] gene resurrection. It disappeared in one of our predessors making us prone to gout and excessive fat d

by xvilka 6y ago

I hope someone works on recovering UOX (Urate Oxidase)[1] gene resurrection. It disappeared in one of our predessors making us prone to gout and excessive fat deposition[2]. Recovering this gene will treat both at the same time. [1] https://www.genecards.org/cgi-bin/carddisp.pl?gene=UOX https://www.genecards.org/cgi-bin/carddisp.pl?gene=UOX [2] https://www.nature.com/articles/s41366-019-0487-9 https://www.nature.com/articles/s41366-019-0487-9

goodells 6y ago
I found the Slate Star Codex article about uric acid interesting [1]. The bit about this gene: > About ten million years ago, the common ancestor of apes and humans got a mutation that broke uricase, causing uric acid levels to rise. The mutation spread very quickly, suggesting that evolution _really_ wanted primates to have lots of uric acid for some reason. Since discovering this, scientists have been trying to figure out exactly what that reason was, with most people thinking it’s probably an antioxidant or neuroprotectant or something else helpful if you’re trying to evolve giant brains. [1] https://slatestarcodex.com/2020/04/27/give-yourself-gout-for-fame-and-profit/ https://slatestarcodex.com/2020/04/27/give-yourself-gout-for...
- graderjs 6y ago
  Maybe it functioned as a pheromone somehow (or pheromone precursor) and was aided by sexual selection: stinkiest mates were more attractive and reproduced more. Hehe. Or might make your flesh pungent and not tasty to predators. The 'stinkiest' fish in the world[1] has high levels of urea (so high that its toxic, and while not uric acid these two molecules are related and both are options in metabolic pathways for processing ammonia) and before eating, hákarl needs to be dried in ice sheds in the artic circle for 3 months. Even then it's acquired taste. Still, it seems unlikely primates were hunted by some unknown predator in such large numbers, for evolution to select for those with slightly more pungent flesh to deter such predation, but ... who knows? :P ;) xx [1]: https://en.wikipedia.org/wiki/H%C3%A1karl https://en.wikipedia.org/wiki/H%C3%A1karl
  - wcarss 6y ago
    Might have suppressed cannibalism!
    - fooker 6y ago
      This is probably the right answer.
astrea 6y ago
Well, not to say that evolution is perfect by any means, but I feel like genetics are very complex and reintroducing that gene could have other side effects.
- causality0 6y ago
  It codes for one protein, and experiments have turned it on and off in other animals. Turning it off benefited humans by increasing the amount of fructose stored as fat during a time when climate change reduced the availability of fruit. In light of our ridiculous modern caloric intake, turning it back on isn't likely to lead to problems.
  - Jarwain 6y ago
    Do you have a source for this? Not asking out of doubt, but curiosity
    - causality0 6y ago
      Kratzer, J., Lanaspa, M., Murphy, M., Cicerchi, C., Graves, C., Tipton, P., Ortlund, E., Johnson, R. and Gaucher, E., 2014. Evolutionary history and metabolic insights of ancient mammalian uricases. Proceedings of the National Academy of Sciences, 111(10), pp.3763-3768
scythe 6y ago
I think you have misread the second paper. Mendelian randomization can be a confusing technique. >Uric acid wGRS was not associated with fasting serum glucose, HbA1C, waist circumference, or BMI. On the other hand, waist circumference was causally associated with all the components of MetS including uric acid. Here's what's happening: some genes are known to be associated with elevated uric acid. Other genes are known to be associated with increased waist circumference. Because several different genes are considered, it is assumed that the "side-effects" of these genes can be neglected; the failure of this assumption is called horizontal pleiotropy, and I don't feel confident assessing their methods on this point. MR is generally considered to provide a better degree of causality estimation than longitudinal data, because the genetic factors can be considered "prior" to other effects. The authors find that the genes associated with uric acid are associated with worse cardiovascular symptoms, while they are not associated with other symptoms of metabolic syndrome; waist circumference genes are associated with all of the symptoms of metabolic syndrome. Also, the effect of weight circumference genes on uric acid levels is significant, while the effect of uric acid genes on waist circumference is not (a strange asymmetry, but I guess it makes sense). So what the study really shows is that elevated uric acid appears to contribute to worse blood parameters. However, it doesn't contribute much to central adiposity.

by xvilka 6y ago

goodells 6y ago

I found the Slate Star Codex article about uric acid interesting [1]. The bit about this gene: > About ten million years ago, the common ancestor of apes and humans got a mutation that broke uricase, causing uric acid levels to rise. The mutation spread very quickly, suggesting that evolution _really_ wanted primates to have lots of uric acid for some reason. Since discovering this, scientists have been trying to figure out exactly what that reason was, with most people thinking it’s probably an antioxidant or neuroprotectant or something else helpful if you’re trying to evolve giant brains. [1] https://slatestarcodex.com/2020/04/27/give-yourself-gout-for-fame-and-profit/ https://slatestarcodex.com/2020/04/27/give-yourself-gout-for...

graderjs 6y ago
Maybe it functioned as a pheromone somehow (or pheromone precursor) and was aided by sexual selection: stinkiest mates were more attractive and reproduced more. Hehe. Or might make your flesh pungent and not tasty to predators. The 'stinkiest' fish in the world[1] has high levels of urea (so high that its toxic, and while not uric acid these two molecules are related and both are options in metabolic pathways for processing ammonia) and before eating, hákarl needs to be dried in ice sheds in the artic circle for 3 months. Even then it's acquired taste. Still, it seems unlikely primates were hunted by some unknown predator in such large numbers, for evolution to select for those with slightly more pungent flesh to deter such predation, but ... who knows? :P ;) xx [1]: https://en.wikipedia.org/wiki/H%C3%A1karl https://en.wikipedia.org/wiki/H%C3%A1karl
- wcarss 6y ago
  Might have suppressed cannibalism!
  - fooker 6y ago
    This is probably the right answer.

astrea 6y ago

Well, not to say that evolution is perfect by any means, but I feel like genetics are very complex and reintroducing that gene could have other side effects.

causality0 6y ago
It codes for one protein, and experiments have turned it on and off in other animals. Turning it off benefited humans by increasing the amount of fructose stored as fat during a time when climate change reduced the availability of fruit. In light of our ridiculous modern caloric intake, turning it back on isn't likely to lead to problems.
- Jarwain 6y ago
  Do you have a source for this? Not asking out of doubt, but curiosity
  - causality0 6y ago
    Kratzer, J., Lanaspa, M., Murphy, M., Cicerchi, C., Graves, C., Tipton, P., Ortlund, E., Johnson, R. and Gaucher, E., 2014. Evolutionary history and metabolic insights of ancient mammalian uricases. Proceedings of the National Academy of Sciences, 111(10), pp.3763-3768

scythe 6y ago

I think you have misread the second paper. Mendelian randomization can be a confusing technique. >Uric acid wGRS was not associated with fasting serum glucose, HbA1C, waist circumference, or BMI. On the other hand, waist circumference was causally associated with all the components of MetS including uric acid. Here's what's happening: some genes are known to be associated with elevated uric acid. Other genes are known to be associated with increased waist circumference. Because several different genes are considered, it is assumed that the "side-effects" of these genes can be neglected; the failure of this assumption is called horizontal pleiotropy, and I don't feel confident assessing their methods on this point. MR is generally considered to provide a better degree of causality estimation than longitudinal data, because the genetic factors can be considered "prior" to other effects. The authors find that the genes associated with uric acid are associated with worse cardiovascular symptoms, while they are not associated with other symptoms of metabolic syndrome; waist circumference genes are associated with all of the symptoms of metabolic syndrome. Also, the effect of weight circumference genes on uric acid levels is significant, while the effect of uric acid genes on waist circumference is not (a strange asymmetry, but I guess it makes sense). So what the study really shows is that elevated uric acid appears to contribute to worse blood parameters. However, it doesn't contribute much to central adiposity.