Ribosome Swap

[drachefly]

Much of our DNA is a code with protein sequences as the message. ATG means Methionine, and CGX (where X is any base) means Arginine, etc. This decoding is performed by the ribosomes.

Ribosomes perform the same coding most creatures on Earth... not ALL.

There are some species of bacteria which have different encoding schema carried out by their ribosomes. Many of these are very minor differences, along the lines of "CGC encodes Leusine, but CGA, CGG, and CGT still encode Arginine", but some are more serious modifications.

Suppose we were to do an ordinary cloning job on some creature, except we completely replace its ribosomes with ribosomes that use another coding, and rewrite its genetic code so that the protein-encoding regions were encoded in this other code.
And further suppose that the resulting creature worked fine. This may not be doable, for a variety of reasons, but just suppose for the moment it did.

Then it would be completely immune to every virus in existence: A virus could take over the cell, and release its DNA to be replicated, and it would... but its DNA also needs to be expressed, to form the body of the virus. And that DNA will be expressed in the wrong encoding, and the virus will not be able to build new bodies.

Nifty!

How long would it take for viruses to jump the gap and be able to infect such creatures?

What difficulties are there aside from the obvious technical troubles of recoding the entire sequence, and replacing every ribosome?

[Broomstick]

Do those oddball species of bacteria have their own viruses? That would seem to throw a wrench in the immunity works.

[drachefly]

There are so few of them, I suspect not. But even if there are, these are viruses evolved to attack bacteria.

And then even if they DO evolve to afflict such creatures, then the viruses they are affected by and the viruses we are affected by would be incompatible.

This would mean, say, that if we did this to HUMANS... ooooh... yeah... then these humans would
A) not be able to reproduce with others humans, but
B) not be able to share viruses with other humans either.
which would be advantageous from a public health perspective.

Kind of like not having one hegemonic operating system on the internet, to bring a computer virus analogy to organic viruses.

[drachefly]

NOTE: the reason I mentioned humans in particular above was if one of them were trained as a doctor to us, he or she would be unable to get sick from our viral diseases... and vice versa. Not just generically less transmissibility, but taking advantage of the total immunity.

Of course, bacteria will still be a problem.

[AMX]

Last I checked, decoding was done by tRNA, not ribosomes.


'Course, you can simply exchange the two in the OP, and carry on.

[drachefly]

Very well. tRNA it is!
(if a mod wants to go fix, be my guest. Or not, whatever)

[Lord Zentei]

Though I'm no professional in this, I would imagine that phages would adapt rather quickly seeing as they outnumber actual cells many times over - seeing their high absolute numbers, the number of "errors" in transcription must be pretty high, leading to numerous new viral candidates.

[drachefly]

Yes; if there is a mechanism by which it can be done, it will be; but I suspect that even error-prone viruses tend not to do wholesale mappings like s/'ATG/'TAG/ homogeneously throughout their genome.

We didn't beat the ID-ers scientifically by invoking the law of large numbers, that was just the grease. We beat them by showing a mechanism.

I'd like to see if there is one here. If there is, that would suggest it would be easier to do it to a creature because we can take advantage of it, but the lesser benefits of reduced cross-infection would still accrue; and if there isn't, then it would be harder but the benefits would be even greater.

[Admiral Valdemar]

There are one or two rare species that show a different codon amino acid code for synthesis, but I don't believe it is all that common. The codons are, for all intents and purposes, universal and only the first two letters code for something, the third is somewhat superfluous but included because of the active site of the ribosome which makes a triplet code the base system.

I can't really say anything that hasn't already been stated, but if such organisms evolved, and there appears evidence for that, then they very likely evolved parasites too. Remember, modern viruses, viroids and so on came about from a pred-prey relationship with a host they were related to. It would, in my eyes, be impossible to have something of any real success evolve without some other lifeform taking advantage of it.

Human engineered species may be an exception, but the universal code for amino acid synthesis is pretty immutable bar the exceptions that involve an organism reassigning a couple of the STOP codons to an amino acid.

[Darth Servo]

Re-writing an entire genome would be one hell of a chore though.

[Admiral Valdemar]

It's not really the writing of the genome, it's the fact that basic biochemistry dictates what makes these rules. You can no more alter it that you can change the Michaelis-Menten pharmacokinetics of any given enzyme. Building an organism from the bottom-up would be a chore and a half anyway.

[drachefly]

Re-writing an entire genome would be one hell of a chore though.

Well, be fair -- you aren't rewriting the entire genome, you're recoding it.

One of the MAIN difficulties, I imagine, would be that some RNA is not intended to be coded into protein, but rather is used structurally. This must not be changed.
To some extent, the tRNA is of this sort; so that there may well be the sort of strong restrictions that Admiral Valdemar refers to, which make this impossible.

That said, I suspect the reason that the differences are minor like encoding something into a STOP slot are just because anything bigger would be such an enormous step that it cannot evolve.
That is, the restriction of evolvability is strong enough to cause the present situation, and we do not need to invoke biochemical law. Not to say that biochemical law couldn't also prohibit it.

[dworkin]

Suppose we were to do an ordinary cloning job on some creature, except we completely replace its ribosomes with ribosomes that use another coding, and rewrite its genetic code so that the protein-encoding regions were encoded in this other code.
And further suppose that the resulting creature worked fine. This may not be doable, for a variety of reasons, but just suppose for the moment it did.

I would be very careful, you can catch all sorts of things at Millyways.

The main problem is energy. Bonds form and break based on their relative stability and how much energy is going arround. This is just as true for all the molecules involved in protien synthesis. One of the reasons the genetic code is almost universal is it's energy efficiency. Most organisms with a variation in the code are, IIRC Archaens which live in rather extreme environments where there is a need for a slightly different set of amino acids for added stability. This takes a bit more energy to do, but extremophiles don't lack for that.

The next is the phenomenal rate at which viruses mutate. Successful viruses are inefficient copiers. This inefficiency is what gives them their great adaptability. I suspect it wouldn't take too long for a virus to make a code jump and it only takes one.

Lastly, your new creatures won't have any immune response to the new viruses either when they turn up. This could well be a Very Bad Thing.

[Darth Servo]

Rewriting or recoding, you're still talking about billions of base pairs. To the best of my knowledge, we can't just substitute a single nucleotide anywhere we want in a previously existing strand. The closest we have are the restriction enzymes which can cut a strand leaving "sticky ends" that allow a short segment of DNA with complimentary "sticky ends" to be added in.

[drachefly]

As I said, it's beyond our present capability to generate genome-sized chunks of arbitrary base pairs. There are methods being devised that could do it. My point is, we would know what to put in, it would just be a question of synthesis.

Lastly, your new creatures won't have any immune response to the new viruses either when they turn up. This could well be a Very Bad Thing.

1) if the viruses in question are human viruses that jumped the gap, then they'll have the antibodies anyway because the viruses will have been wandering around their system ineffectively a long time before becoming virulent.

2) if the viruses in question are archaeo-bacterial viruses that switched species, then they have no techniques for evading a coherent immune system.

So, though it COULD be a bad thing, I doubt it would.


As for the other point, about the energy, I'm not sure I get the point. Are you saying that all existent variants have just edited the code to include amino acids which are more stable and we don't even use because they cost too much energy to make?
All right, then. We won't use those variants.

Or are you saying that the actual mapping of DNA -> proten that we have is in some way energy superior to any other radically different mapping?

[dworkin]

1) if the viruses in question are human viruses that jumped the gap, then they'll have the antibodies anyway because the viruses will have been wandering around their system ineffectively a long time before becoming virulent.

What do you mean by if? When viruses jump they will have radically different coats that your new code demands. The virus itself is likely to be quite a radical varient than not. No fucking idea what it'll do.

However medicine's track record of overestimating our technological prowess is not encouraging.

2) if the viruses in question are archaeo-bacterial viruses that switched species, then they have no techniques for evading a coherent immune system.

Which has no real counters for such viruses because they never were affected by them before. Bad Things happen typically in such scenarios.

Or are you saying that the actual mapping of DNA -> proten that we have is in some way energy superior to any other radically different mapping?

Yes. The reason why one system operates in nature and not another has a lot to do with energy. The more stable processes survive. It's something noticable with the extrmeophiles with slightly different codes. Their DNA composition is different to make for stronger bonding between the two chains. The slightly different code is to produce protiens that are functional at higher tempertures and it requires more energy. However that's not something they lack.

Also the differences between any particular code are likely to be very small. However, over time those differences matter. Every molecule in your body is 'left-handed' due to L-isomers being 1/1000000000000000000 more stable than R-isomers for example.

[drachefly]

1) if the viruses in question are human viruses that jumped the gap, then they'll have the antibodies anyway because the viruses will have been wandering around their system ineffectively a long time before becoming virulent.

What do you mean by if? When viruses jump they will have radically different coats that your new code demands. The virus itself is likely to be quite a radical varient than not. No fucking idea what it'll do.

I was supposing that in order to 'jump the gap' it would not change its protein structure, just choose a genetic code that would work the same in either coding.

Note that outside the transcriptional apparatus, the proteins in the modified critter are identical to those in the unmodified one.

2) if the viruses in question are archaeo-bacterial viruses that switched species, then they have no techniques for evading a coherent immune system.

Which has no real counters for such viruses because they never were affected by them before. Bad Things happen typically in such scenarios.

Bad things happen when a virus which is competent to attack, say, a bird, transfers to a human, sure. But birds are a hell of a lot closer to humans than archaeobacteria are... and I think such viruses would be a lot closer to our everyday viruses than that.

The more stable processes survive. It's something noticable with the extrmeophiles with slightly different codes. Their DNA composition is different to make for stronger bonding between the two chains. The slightly different code is to produce protiens that are functional at higher tempertures and it requires more energy. However that's not something they lack.

When you say the DNA composition is different, do you mean the coding is different, or do you mean that they tend to use more A's than T's?

And if it's just the coding, then do you mean that this other coding is less energy efficient at producing proteins that do not involve the amino acids we can't produce?
If so, how much?

[dworkin]

I was supposing that in order to 'jump the gap' it would not change its protein structure, just choose a genetic code that would work the same in either coding.

Any viral code that can produce a new protein coat will be making a different one.

Note that outside the transcriptional apparatus, the proteins in the modified critter are identical to those in the unmodified one.

I'll concede that it'll be a damn good fix for a long time from a human perspective but that's just it.

Bad things happen when a virus which is competent to attack, say, a bird, transfers to a human, sure. But birds are a hell of a lot closer to humans than archaeobacteria are... and I think such viruses would be a lot closer to our everyday viruses than that.

Good point. The problem of what happens if an archaen specific virus suddenly has an easier time infecting such a critter is just a total unknown.

When you say the DNA composition is different, do you mean the coding is different, or do you mean that they tend to use more A's than T's?

Extremophile DNA has more G-C pairs for increased stability of it's structure. It's a good example of bond energies determining the composition of large molecules in organisms as is the total left handed bias.

And if it's just the coding, then do you mean that this other coding is less energy efficient at producing proteins that do not involve the amino acids we can't produce?
If so, how much?

The DNA takes more energy to take apart and then reanneal, the proteins need more enrgy to assemble. The whole process takes more energy for the price of greater heat stability.

High GC bias is essential to heat stability of t-RNA allowing for functionality above 333 K. (60 degrees C). Since some extremeophiles function happily in boiling mud pools and geysers the difference can be quite pronounced.

Your putative recoded critters may end up needing more energy to run themselves. It may be a trivial amount that results in an extra packet of chocy bikkies each year. But that's enough to be selective over evolutionary time even if that's not an issue for the individual GELFs.

Another consideration is viral insertions. Many varieties of virus insert themselves into the genome before cutting loose with hyper production that eventually kills the cell. Since these modded critters won't have trouble with being destroyed this may increase the rate of viral insertion radically. Of course for a society that can rewrite their entire genome this may not be such a major problem. You might end up getting 'gene-cleaned' once a year instead of a flu-shot.

[dworkin]

And thanks drachefly for an interesting thought-experiment. This may be a more modern explanation of what happened to Well's Martiians, who as we know did something funky to their immune system. They may of just been supremly unlucky in that the jump happened inside of two weeks rather than 2,000 years.

[His Divine Shadow]

It's not really the writing of the genome, it's the fact that basic biochemistry dictates what makes these rules. You can no more alter it that you can change the Michaelis-Menten pharmacokinetics of any given enzyme. Building an organism from the bottom-up would be a chore and a half anyway.

Still it's gonna be done some day. I hope.