October 01, 2013
Your Genome: Full Of Wreckage From Ancient Genetic Battles
I pass this along to you mostly because it sounds so dramatic, brutal, and severe: your genome is an old battlefield. It is a mess. Do not romanticize your genome as a highly tuned and optimized control center working cleanly for your benefit.
Contrary to what you may have heard, your genome is not a highly sophisticated, finely tuned data storage and processing device. Itís a post-apocalyptic wasteland. Your 25,000 genes reside in a genetic landscape littered with the rubble of ancient and ongoing battles with hordes of viruses, clone armies of genetic parasites, and zombie genes that should be dead but arenít.
Even more important, we've got genetic load as a much bigger problem in our genome. We've all got lots of slightly harmful mutations that show up each generation mostly randomly. Not due to ancient battles between viruses and other parasites.
If I could genetically change one thing about myself I'd get rid of all the accumulated genetic load mutations. I'd suddenly become healthier (not that I'm sick), happier (not that I'm depressed either), and much smarter (which I'd really like to be). Even if you aren't sick or depressed or dumb you could still have a much greater sense of good health and well being if your body was made to run far more effectively then you can now with your mutation-laden genome with many centuries of accumulations of little mistakes.
Since we've exited the Malthusian Trap successive generations have been accumulating more genetic load. We need biotechnologies that will let us clean it up. I hope to live long enough to get their benefits. Imagine rejuvenating stem cell therapies where as part of the preparation to turn your cells into stem cells their genomes get edited to remove large numbers of harmful mutations. As those cells spread across your body various organs would start functioning better than they did ever before in your life. That would be cool.
Randall Parker, 2013 October 01 09:25 PM
Indeed. I think one of the ultimate goals of genetic engineering is to reverse engineer the human genome, clear out all the garbage, and recompile. Even without any actual improvements to the code that's executing, that would improve our health immensely, as well as allowing us to have a much more compact genome.
Today's genetic load may be tomorrow's genetic advantage (and vice versa) as the environment changes. If you clean up all that "garbage" in sperm and eggs, you reduce the resources your descendants have to face environmental shocks.
Clark: in most cases, probably not. There certainly are cases where mutations are mostly harmful but slightly ambiguous, but a lot of the genetic load is just purely broken stuff. We're not really talking about natural variation here. There would still be plenty of that left even after all of the junk was removed. Now, granted, if you remove the load based on purely statistical analysis (rather than knowledge of function) you *may* end up getting rid of some rare beneficial mutation, but that's not the way to bet.
No, Clark Cooper is absolutely right. However, he has neglected to add the other half of the 'engine' that makes diversity work: selection. Genetic drift only ends up being helpful, that is to say, the answer to changing environments, if massive numbers of individuals can be selected out (i.e., killed off) with relatively few lineages surviving. That's the way nature works, and the reason for that is because that's the *only* way it *can* work.
Hence my own long term plan for personal survival in a world where the only certain thing is change: release massive numbers of my clones (complete with unavoidable transcription errors) into the environment, and have an ongoing process of culling the relatively unsuccessful ones and transcribing the genomes of the best ones, and then incorporating favourable changes into my own personal cell lines. One useful side effect of this strategy is it equips you with a large clone army, which may be vital in times to come.
"release massive numbers of my clones"
Being clones, they'd lack the wide ranging adaptability need for long term survival.
All human philosophy to the contrary, life isn't about individual survival; it's about species survival. Darwin knew that.
I wouldn't worry too much about the escape from the Malthusian trap degrading the average person's genetic health. It's been a long time since the average European has had to chase down their dinner through endurance running and yet people of European descent still win plenty of olympic marathon medals. So while there may well be non-European populations that have a gentic advantage advantage when it comes to long distance running the advantage doesnt' seem to be large enough to consistently take home the medals. If something was very important for survival in the past it can take a very long time for it to drift away. Of course, one can't read too much into olympic medal results when it comes to genetics, otherwise one would have to conclude that Australians are genetically superior.
We don't know nearly enough about the genome at this point to make changes without a compelling reason. If we did then we'd already be able to cure any disease or regrow any organ. We'd even be able to prolong lives indefinitely. We're clearly not at that point yet. We couldn't even delete the genetic load even if we wanted to. Ergo, we still have a lot to learn before meddling with it.
Besides, if all this genetic load was statistically harmful then natural selection would have already minimized it to the statistically optimum level. Not that too much genetic load is a good thing. But a certain amount is necessary. It's just that most mutations are harmful. So most genetic load is harmful. Harmful or not, it's still necessary. It's the fodder upon which evolution is built. Deleting it may eliminate some diseases. But it would cost us the capacity to adapt and lead to humanity's extinction.
I'm not opposed to making changes. I'm opposed to making uneducated changes.
Once we have cleaned up our genome we would need the naked mole rats ribosome to reduce copying errors.
I'd like to know what the trade-offs would be for using more accurate ribosomes. Do they translate at a slower rate?
I also wonder whether massive computer sims could go thru lots of alternative designs for ribosomes and come up with a design that would have lower rates without any undesired trade-offs.
Genetic load exists because mutations that cause small amounts of harm pop up at a faster rate than natural selection can get rid of them.
What we need to know: which low frequency mutations are pure harmful, a mix of harmful and beneficial, pure beneficial, or neutral. If we can come up with ways to identify large numbers of purely harmful mutations then we could eliminate them without loss.
Right now each of us has probably hundreds of pure harmful mutations. I'd love to get rid of mine because if I could I'd operate at a much higher level of efficiency, efficacy, and happiness.
The vast majority of people can not win Olympic medals. The winners have lower genetic load than the average person. What the Olympic medal winners demonstrate is just how much more capable we could be if we reduced our genetic load. The very brightest and accomplished people also demonstrate how much the rest of us are missing out on by carrying around lots of harmful mutations.
Maybe our junk dna isnt all junk, some could be from ancient aliens that created us? By reverse engineering our genomes we will eventualy find out.
To run as fast as Usain Bolt certainly requires the right genetics. But go to any high school sports day in Japan or China and you'll see that, despite having thousands of years of agriculture under their genetic belts, the majority of students run the 100 metres at a good portion of Bolt's world record. Traits that were vital to survival tend to be well conserved and so hang around for a long time even after selection pressure is reduced.