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* 'Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNA—and RNA—that were not thought to

* 'Small proteins also promise to revise the current understanding of the genome. Many appear to be encoded in stretches of DNA—and RNA—that were not thought to help build proteins of any sort. Some researchers speculate that the short stretches of DNA could be newborn genes, on their way to evolving into larger genes that make full-size proteins. Thanks in part to small proteins, "We need to rethink what genes are," says microbiologist and molecular biologist Gisela Storz of the National Institute of Child Health and Human Development in Bethesda, Maryland.' Wow. Amazing how incredible biology and proteins are and their still-barely-understood mechanisms. For anyone who hasn't already seen it, I highly recommend The Inner Life of a Cell [0] [0] https://www.youtube.com/watch?v=wJyUtbn0O5Y https://www.youtube.com/watch?v=wJyUtbn0O5Y

danharaj 7y ago
This is why you should be very skeptical of anyone who claims transparency between genetics and complex phenotypes.
- dfsegoat 7y ago
  Indeed. The whole "One Gene, One Protein [One Phenotype]" [1] dogma went out quite some time ago. ... But people and genetic testing companies seem to want to keep it going. [1] - https://embryo.asu.edu/pages/george-w-beadles-one-gene-one-enzyme-hypothesis https://embryo.asu.edu/pages/george-w-beadles-one-gene-one-e...
  - dboreham 7y ago
    We will eventually find that there's the equivalent of JPEG encoding (plus SSL and ECC) and that today we're doing the equivalent of someone with no knowledge of SSL or JPEG staring at a tcpdump trace of a browser loading an image over https, trying to make sense of the resulting hex dump.
    - q6467655 7y ago
      Can you elaborate - I’ve always been fascinated hearing CS interpretations of biological processes.
      - kevin_thibedeau 7y ago
        DNA methylation acts as a form of error correction analogous to parity.
        wjn0 7y ago
        If genes are the data, then methylation is more like an additional piece of metadata directing the cell (potentially different across cells) how to use the data. One possible use for this metadata is potentially error correction, but it does much more than that.
        JohnBerea 7y ago
        And alternate splicing is a form of compression, where exons store the repetitive parts of genes only once, to be combined to make many proteins.
    - theLotusGambit 7y ago
      Trying to figure out how a single compressed/encrypted buffer works given only it and its resulting image is certainly an unwinnable task, but increase the sample size to a few million or billion and I don't see why the algorithm couldn't eventually be cracked.
    - meowface 7y ago
      Great analogy. This might be the case with some of physics, too.
  - wahern 7y ago
    > But people and genetic testing companies seem to want to keep it going. You can still get alot of mileage out of a simplified, inaccurate model. If you just say to yourself, "well, this whole gene thing is hopelessly complex", then you'll never get anywhere outside of a lab or personal project. Applied biology especially, and medicine in particular, seems to require grossly simplifying assumptions in order to make any problem tractable. I would think that would be understood by people on HN. One of the biggest impediments to smart people starting companies is an inability to set aside the inherent, irreducible complexity that they, alone, see and appreciate. The people who succeed in business tend to be those ignorant of the complexity[1], or those able to come to terms with the reality that any practical, marketable solution is necessarily built on an inaccurate model of the world and is doomed to eventually crumble for its inherent flaws. The old adage that ignorance is bliss is more insightful and meaningful than people give it credit for. Knowledge, especially epistemic knowledge, can be debilitating. [1] Which doesn't imply being stupid or incurious. Willful ignorance seems like a potentially useful strategy.
    - navaati 7y ago
      You are basically saying "lying to people can make you some money". Indeed…
- hyperbovine 7y ago
  The genetic basis of complex traits was the biggest open problem in science (IMO) long before this discovery came along.
- aiphex 7y ago
  Which is why I have zero interest in things like 23 and me. I worked in a genetics lab and the longer I worked there, the more I realized how little we understand.
  - RhodesianHunter 7y ago
    Sure, we don't understand much detail but we know a whole lot of things like "you're x% more likely to get y disease", and if y is something that can be monitored or tested for, this can literally save your life. BRCA and heart disease come to mind.
- ddiq 7y ago
  That doesn't really follow. We don't need to have a complete map genotype to phenotype in order to have an understanding of the weight of genetic component of certain traits. Just because we don't know exactly which genes cause a certain hair color doesn't mean we can't guess which parents are more likely to have children with that hair color. The same goes for behavior that can be measured and predicted. As long as that prediction is more accurate than a random guess, the prediction has value.
  - beambot 7y ago
    If you drop an apple & observe that it falls, you get some predictive value about the nature of gravity. But that's a far cry from computing the orbital dynamics of a spacecraft. Parent's comment on "transparency" in the mapping from genotype to phenotype was more akin to the latter -- and their point stands.
    - danharaj 7y ago
      You can read their comment history to contextualize their angle.
    - rdlecler1 7y ago
      We sent astronauts to the moon with Newtonian physics. No need for relativity. This is more akin to relativity in that it expands our domain knowledge and explanatory power but the old model already does most of the work.
    - ddiq 7y ago
      Do you not think studying gravity lead to predictive value before we reached a point of being able to compute orbital dynamics of a spacecraft?
Dev_2019 7y ago
We aren't curing aging any time soon are we :(?
- LinuxBender 7y ago
  Several companies and research groups are working on it. The challenge is a lack of priority, funding and even recognizing aging as a disease, at least in legal terms. Look up the Sens foundation (Dr. Aubrey De Grey), Dr. David Sinclair (Harvard .. Some are skeptical because he has started several companies) and Dr. Bruce Ames as starting points.
  - Retric 7y ago
    I think the real challenge is mind boggling complexity of interactions. Suggesting it’s a question of funding etc is vastly understating the actual issues. Curing cancer for example is a vastly simpler problem.
    - LinuxBender 7y ago
      Don't get me wrong, it is a very complex set of complex issues depending on which pillar we attack. (Metabolism, Repair, Pathology). The latter is very expensive and too late in the game. That is what we attempt today with conventional medicine and it's just treating symptoms of aging. We barely understand human metabolism and the little bit we know is a auditorium wall sized flow chart. Repair is the new area and Aubrey is putting a lot of effort into that pillar. That is where funding would certainly help. Then there are legal and ethical issues we will eventually dive in to.
    - sasaf5 7y ago
      Not only simpler, curing cancer is also necessary for curing aging.
      - LinuxBender 7y ago
        Absolutely. There is already a great deal of work on the metabolic side, such as removing biofilms of cancer with AGE (aged garlic extract), slowing or stopping metastases with bio-availability enhanced Curcumin, up-regulating autophagy and cell apoptosis with the up-regulation of NRF2 via cycling Sulforaphane and Myrosinase, starving cancer cells by removing all glucose and processed carbs via Keto and intermittent fasting, 5 day FMD (fast mimicking diet). All of these things highly complement Chemo, increasing the effectiveness and mitigating much of the damage caused by Chemo Therapy. On the repair pillar, quite a bit of work is being done with CRISPR to attack cancer cells. There is also research on targeting specific cells using sound (11th harmonics) and destroying them. Sorry I don't have any links to share. I must get back to work. :-)

danharaj 7y ago

This is why you should be very skeptical of anyone who claims transparency between genetics and complex phenotypes.

dfsegoat 7y ago
Indeed. The whole "One Gene, One Protein [One Phenotype]" [1] dogma went out quite some time ago. ... But people and genetic testing companies seem to want to keep it going. [1] - https://embryo.asu.edu/pages/george-w-beadles-one-gene-one-enzyme-hypothesis https://embryo.asu.edu/pages/george-w-beadles-one-gene-one-e...
- dboreham 7y ago
  We will eventually find that there's the equivalent of JPEG encoding (plus SSL and ECC) and that today we're doing the equivalent of someone with no knowledge of SSL or JPEG staring at a tcpdump trace of a browser loading an image over https, trying to make sense of the resulting hex dump.
  - q6467655 7y ago
    Can you elaborate - I’ve always been fascinated hearing CS interpretations of biological processes.
    - kevin_thibedeau 7y ago
      DNA methylation acts as a form of error correction analogous to parity.
      - wjn0 7y ago
        If genes are the data, then methylation is more like an additional piece of metadata directing the cell (potentially different across cells) how to use the data. One possible use for this metadata is potentially error correction, but it does much more than that.
      - JohnBerea 7y ago
        And alternate splicing is a form of compression, where exons store the repetitive parts of genes only once, to be combined to make many proteins.
  - theLotusGambit 7y ago
    Trying to figure out how a single compressed/encrypted buffer works given only it and its resulting image is certainly an unwinnable task, but increase the sample size to a few million or billion and I don't see why the algorithm couldn't eventually be cracked.
  - meowface 7y ago
    Great analogy. This might be the case with some of physics, too.
- wahern 7y ago
  > But people and genetic testing companies seem to want to keep it going. You can still get alot of mileage out of a simplified, inaccurate model. If you just say to yourself, "well, this whole gene thing is hopelessly complex", then you'll never get anywhere outside of a lab or personal project. Applied biology especially, and medicine in particular, seems to require grossly simplifying assumptions in order to make any problem tractable. I would think that would be understood by people on HN. One of the biggest impediments to smart people starting companies is an inability to set aside the inherent, irreducible complexity that they, alone, see and appreciate. The people who succeed in business tend to be those ignorant of the complexity[1], or those able to come to terms with the reality that any practical, marketable solution is necessarily built on an inaccurate model of the world and is doomed to eventually crumble for its inherent flaws. The old adage that ignorance is bliss is more insightful and meaningful than people give it credit for. Knowledge, especially epistemic knowledge, can be debilitating. [1] Which doesn't imply being stupid or incurious. Willful ignorance seems like a potentially useful strategy.
  - navaati 7y ago
    You are basically saying "lying to people can make you some money". Indeed…
hyperbovine 7y ago
The genetic basis of complex traits was the biggest open problem in science (IMO) long before this discovery came along.
aiphex 7y ago
Which is why I have zero interest in things like 23 and me. I worked in a genetics lab and the longer I worked there, the more I realized how little we understand.
- RhodesianHunter 7y ago
  Sure, we don't understand much detail but we know a whole lot of things like "you're x% more likely to get y disease", and if y is something that can be monitored or tested for, this can literally save your life. BRCA and heart disease come to mind.
ddiq 7y ago
That doesn't really follow. We don't need to have a complete map genotype to phenotype in order to have an understanding of the weight of genetic component of certain traits. Just because we don't know exactly which genes cause a certain hair color doesn't mean we can't guess which parents are more likely to have children with that hair color. The same goes for behavior that can be measured and predicted. As long as that prediction is more accurate than a random guess, the prediction has value.
- beambot 7y ago
  If you drop an apple & observe that it falls, you get some predictive value about the nature of gravity. But that's a far cry from computing the orbital dynamics of a spacecraft. Parent's comment on "transparency" in the mapping from genotype to phenotype was more akin to the latter -- and their point stands.
  - danharaj 7y ago
    You can read their comment history to contextualize their angle.
  - rdlecler1 7y ago
    We sent astronauts to the moon with Newtonian physics. No need for relativity. This is more akin to relativity in that it expands our domain knowledge and explanatory power but the old model already does most of the work.
  - ddiq 7y ago
    Do you not think studying gravity lead to predictive value before we reached a point of being able to compute orbital dynamics of a spacecraft?

Dev_2019 7y ago

We aren't curing aging any time soon are we :(?

LinuxBender 7y ago
Several companies and research groups are working on it. The challenge is a lack of priority, funding and even recognizing aging as a disease, at least in legal terms. Look up the Sens foundation (Dr. Aubrey De Grey), Dr. David Sinclair (Harvard .. Some are skeptical because he has started several companies) and Dr. Bruce Ames as starting points.
- Retric 7y ago
  I think the real challenge is mind boggling complexity of interactions. Suggesting it’s a question of funding etc is vastly understating the actual issues. Curing cancer for example is a vastly simpler problem.
  - LinuxBender 7y ago
    Don't get me wrong, it is a very complex set of complex issues depending on which pillar we attack. (Metabolism, Repair, Pathology). The latter is very expensive and too late in the game. That is what we attempt today with conventional medicine and it's just treating symptoms of aging. We barely understand human metabolism and the little bit we know is a auditorium wall sized flow chart. Repair is the new area and Aubrey is putting a lot of effort into that pillar. That is where funding would certainly help. Then there are legal and ethical issues we will eventually dive in to.
  - sasaf5 7y ago
    Not only simpler, curing cancer is also necessary for curing aging.
    - LinuxBender 7y ago
      Absolutely. There is already a great deal of work on the metabolic side, such as removing biofilms of cancer with AGE (aged garlic extract), slowing or stopping metastases with bio-availability enhanced Curcumin, up-regulating autophagy and cell apoptosis with the up-regulation of NRF2 via cycling Sulforaphane and Myrosinase, starving cancer cells by removing all glucose and processed carbs via Keto and intermittent fasting, 5 day FMD (fast mimicking diet). All of these things highly complement Chemo, increasing the effectiveness and mitigating much of the damage caused by Chemo Therapy. On the repair pillar, quite a bit of work is being done with CRISPR to attack cancer cells. There is also research on targeting specific cells using sound (11th harmonics) and destroying them. Sorry I don't have any links to share. I must get back to work. :-)