5 ms·

It would be interesting to see if we could clean up (refactor) the human genetic code into a more efficient form with less baggage, and maybe less chance at get

by karsus 12y ago

It would be interesting to see if we could clean up (refactor) the human genetic code into a more efficient form with less baggage, and maybe less chance at getting hit by viruses just by virtue of having fewer random flaws to exploit.

hayksaakian 12y ago
the main issue is that we only really know what a fraction of the human genetic code is directly responsible for. we would need a lot of experimentation to figure out what's safe to remove. you can think about it as a physical "dependency hell"
- qnaal 12y ago
  unfortunately eugenics is immoral or something
- karsus 12y ago
  If we could simulate human cells completely, we could try to simulate an embryo's initial formation and see what falls apart if you remove various sequences. Besides that... we need to understand how a cell recognizes its purpose in its local environment - some kind of local communication probably. If we knew what the various environments that control cell responses are, we would have the basis for something like unit tests... and then we could try randomly removing parts of the DNA and see if its failing to perform as expected or not.
pmalynin 12y ago
Actually that's an incredibly terrible idea. You see single base-pair (and other) errors are very common during DNA replication. By having a lot of "useless" (allegedly) zones in our DNA, decreases, statistically speaking, chances of that error occurring in more important areas.
- Retr0spectrum 12y ago
  Could you explain why that is the case? It seems unintuitive.
  - deleted 12y ago
    [deleted]
  - Snail_Commando 12y ago
    Imagine a general with a finite amount of artillery shells and a Howitzer on the fritz (i.e. the intended trajectory of the shots are somewhat off the mark today). Given the choice of where to deploy the artillery, the general may choose to concentrate their fire on the narrow beachhead landing instead of upon a widely scattered formation of units approaching across a vast plain. The artillery that lands on the plain may strike an advancing unit, or it may fall (possibly harmlessly) between a set of advancing units. The artillery that lands on the narrow beachhead is more likely to hit a unit. This analogy is far from perfect: sometimes mutations are good, which is one primary driver of evolution. Non-coding regions and/or "baggage to be refactored" (paraphrased great-great-gp comment) in DNA (the regions of the plain/beach not occupied by an advancing unit) can absorb "errors". Also, there are other types of mutations (insertions, deletions, ...), aside from the single point mutations that this analogy was attempting to help convey. The point is: it's like bunching up a lot of important things over a few points of failure. If you increase "the genetic surface area", you lower the chance of the important thing getting hit. On evolutionary scales, viable DNA has been selected with a lot of non-coding (and sometimes useful) regions, we know that if we reduce that down, we are more likely to be susceptible to fatal mutations on coding regions (e.g. a region that codes for a vital protein).
    - codeflo 12y ago
      I think that's not the best analogy. You're imagining a constant amount of mutations (artillery shells) spreading over the size of the genome (the beach). It doesn't quite work like that, which is why mutation rates are usually measured in errors per base pair per generation. In fact, copying DNA is more like downloading a large file over an unreliable network. There's a certain chance that each individual bit is flipped and the file becomes useless. You can reduce that chance by sending it multiple times, or introducing checksums, both of which add redundant data. But simply adding an extra TB of junk bytes to your download won't help preserve the integrity of the original file.
- tzs 12y ago
  That's unexpected. Why would it behave that way? The animations I've seen that purport to show the general public how DNA replication works indicate that it is a sequential process. The DNA is split into two strands, kind of like a zipper unzipping, and then bases are added to the two strands to form the two new complete DNA molecules. One strand (the leading strand) has the new bases added one after the other in the same direction. The other strand (the lagging strand) has them added in short called Okazaki fragments. Errors on the leading strand should be independent and occur at a constant rate, and so having useless zones should have no effect on the number of errors a given useful zone gets. The lagging strand is more complicated, because you have at least 3 distinct things going on: finding where to start on Okazaki fragment, filling it in, and recognizing the end. I suppose that allows for a different kind of error on the lagging strand (messing up recognizing the start or end of an Okazaki fragment) that would affect multiple consecutive base pairs. Useless segments would increase the average spacing between useful segments, and so would decrease the chance that a given multi-base error in a useful fragment affects multiple segments.
  - pmalynin 12y ago
    The process you described is correct. However, the problem here is that the enzymes aren't perfect and coding errors are quite common (they get fixed, sometimes). A big problem is that some chemicals can look like a nucleotide (A or T or C or G) and after insertion it can "decay" into a different one, hence causing an error. During replication it is possible for a DNA fragment to be cleaved (once again, it is often repaired, but thats how the Y chromosome came to be AFAIK) however sometimes enzymes "mess up" and reattach them at wrong positions. At other times base-pairs are deleted or inserted shifting the whole strand. There is a lot of things that could go wrong.
- JoeAltmaier 12y ago
  I don't believe that argument. Why would an error transcribing a virus dna segment affect in any way, the probability of error transcribing useful dna? They would be independent variables. Removing duplicates of Useful segments could be bad - one gets mis-copied, the other is still there and so partial function would remain.
- ajuc 12y ago
  Longer code = more chances to make a mistake copying it. You assumed error chance doesn't depend on the code lenght.
noonespecial 12y ago
I think it's a mistake to consider a "clean" version of the human genome that "got polluted" along the way. We co-evolved with these other factors all together. Tinker at your own risk.
- JoeAltmaier 12y ago
  Yeah but chimps and denisovans lived fine without as many copies. Certainly I don't advise knocking about indiscriminately. But we have 100 copies - wouldn't 50 do? 20? 1?
kenrikm 12y ago
In many cases these can be thought of as "bug fixes" cleaning it up might expose us to even more issues.
marbu 12y ago
Think of DNA as a binary code. It's not a source code we are able to understand or refactor.

by karsus 12y ago

hayksaakian 12y ago

the main issue is that we only really know what a fraction of the human genetic code is directly responsible for. we would need a lot of experimentation to figure out what's safe to remove. you can think about it as a physical "dependency hell"

qnaal 12y ago
unfortunately eugenics is immoral or something
karsus 12y ago
If we could simulate human cells completely, we could try to simulate an embryo's initial formation and see what falls apart if you remove various sequences. Besides that... we need to understand how a cell recognizes its purpose in its local environment - some kind of local communication probably. If we knew what the various environments that control cell responses are, we would have the basis for something like unit tests... and then we could try randomly removing parts of the DNA and see if its failing to perform as expected or not.

pmalynin 12y ago

Actually that's an incredibly terrible idea. You see single base-pair (and other) errors are very common during DNA replication. By having a lot of "useless" (allegedly) zones in our DNA, decreases, statistically speaking, chances of that error occurring in more important areas.

Retr0spectrum 12y ago
Could you explain why that is the case? It seems unintuitive.
- deleted 12y ago
  [deleted]
- Snail_Commando 12y ago
  Imagine a general with a finite amount of artillery shells and a Howitzer on the fritz (i.e. the intended trajectory of the shots are somewhat off the mark today). Given the choice of where to deploy the artillery, the general may choose to concentrate their fire on the narrow beachhead landing instead of upon a widely scattered formation of units approaching across a vast plain. The artillery that lands on the plain may strike an advancing unit, or it may fall (possibly harmlessly) between a set of advancing units. The artillery that lands on the narrow beachhead is more likely to hit a unit. This analogy is far from perfect: sometimes mutations are good, which is one primary driver of evolution. Non-coding regions and/or "baggage to be refactored" (paraphrased great-great-gp comment) in DNA (the regions of the plain/beach not occupied by an advancing unit) can absorb "errors". Also, there are other types of mutations (insertions, deletions, ...), aside from the single point mutations that this analogy was attempting to help convey. The point is: it's like bunching up a lot of important things over a few points of failure. If you increase "the genetic surface area", you lower the chance of the important thing getting hit. On evolutionary scales, viable DNA has been selected with a lot of non-coding (and sometimes useful) regions, we know that if we reduce that down, we are more likely to be susceptible to fatal mutations on coding regions (e.g. a region that codes for a vital protein).
  - codeflo 12y ago
    I think that's not the best analogy. You're imagining a constant amount of mutations (artillery shells) spreading over the size of the genome (the beach). It doesn't quite work like that, which is why mutation rates are usually measured in errors per base pair per generation. In fact, copying DNA is more like downloading a large file over an unreliable network. There's a certain chance that each individual bit is flipped and the file becomes useless. You can reduce that chance by sending it multiple times, or introducing checksums, both of which add redundant data. But simply adding an extra TB of junk bytes to your download won't help preserve the integrity of the original file.
tzs 12y ago
That's unexpected. Why would it behave that way? The animations I've seen that purport to show the general public how DNA replication works indicate that it is a sequential process. The DNA is split into two strands, kind of like a zipper unzipping, and then bases are added to the two strands to form the two new complete DNA molecules. One strand (the leading strand) has the new bases added one after the other in the same direction. The other strand (the lagging strand) has them added in short called Okazaki fragments. Errors on the leading strand should be independent and occur at a constant rate, and so having useless zones should have no effect on the number of errors a given useful zone gets. The lagging strand is more complicated, because you have at least 3 distinct things going on: finding where to start on Okazaki fragment, filling it in, and recognizing the end. I suppose that allows for a different kind of error on the lagging strand (messing up recognizing the start or end of an Okazaki fragment) that would affect multiple consecutive base pairs. Useless segments would increase the average spacing between useful segments, and so would decrease the chance that a given multi-base error in a useful fragment affects multiple segments.
- pmalynin 12y ago
  The process you described is correct. However, the problem here is that the enzymes aren't perfect and coding errors are quite common (they get fixed, sometimes). A big problem is that some chemicals can look like a nucleotide (A or T or C or G) and after insertion it can "decay" into a different one, hence causing an error. During replication it is possible for a DNA fragment to be cleaved (once again, it is often repaired, but thats how the Y chromosome came to be AFAIK) however sometimes enzymes "mess up" and reattach them at wrong positions. At other times base-pairs are deleted or inserted shifting the whole strand. There is a lot of things that could go wrong.
JoeAltmaier 12y ago
I don't believe that argument. Why would an error transcribing a virus dna segment affect in any way, the probability of error transcribing useful dna? They would be independent variables. Removing duplicates of Useful segments could be bad - one gets mis-copied, the other is still there and so partial function would remain.
ajuc 12y ago
Longer code = more chances to make a mistake copying it. You assumed error chance doesn't depend on the code lenght.

noonespecial 12y ago

I think it's a mistake to consider a "clean" version of the human genome that "got polluted" along the way. We co-evolved with these other factors all together. Tinker at your own risk.

JoeAltmaier 12y ago
Yeah but chimps and denisovans lived fine without as many copies. Certainly I don't advise knocking about indiscriminately. But we have 100 copies - wouldn't 50 do? 20? 1?

kenrikm 12y ago

In many cases these can be thought of as "bug fixes" cleaning it up might expose us to even more issues.

marbu 12y ago

Think of DNA as a binary code. It's not a source code we are able to understand or refactor.