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New organisms have been formed using the first ever 6-letter genetic code

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Re: New organisms have been formed using the first ever 6-letter genetic code

#71

Post by 88e282102ae2e5b »

oever wrote: post #38
ambrop7 wrote: post #26

Can the organism replicate the XY pairs during DNA replication (and pass it on to divided cells)? I haven't seen that mentioned, only that it "holds onto it for its entire lifespan" which is not clear to me. There's also nothing about the interaction of these pairs with existing mechanisms, like transcription (DNA-->RNA) and translation (RNA-->protein). Could the new new pair increase the space of aminoacids from whi…

The XY pairs are not replicated. To replicate them would require the presence of a slew of specialized proteins that can deal with XY pairs. The achievement is that the E. Coli lifetime is not affected. The XY's are probably inserted in a part of the DNA that is not transcribed.

The paper specifically states that these unnatural base pairs were chosen because they can be handled by natural polymerases. Also, the only way to maintain a plasmid over time is to replicate it. In fact, the whole logic of the strategy is to have Cas9 target mutations to the plasmid so that loss of the XY base pair during replication would lead to loss of the plasmid, and thus loss of the antibiotic resistance gene that it also carried.

Re: New organisms have been formed using the first ever 6-letter genetic code

#72

Post by vivekd »

So will this actually mean anything? Can adding extra letters to an organisms genetic code actually have the capacity to change it's attributes in any meaningful way. Every biological characteristic on the planet seems to have been achieved through using the same 4 molecules, will the addition of more molecules create new characteristics or be useful in any way?

Re: New organisms have been formed using the first ever 6-letter genetic code

#73

Post by 88e282102ae2e5b »

ambrop7 wrote: post #26

Can the organism replicate the XY pairs during DNA replication (and pass it on to divided cells)? I haven't seen that mentioned, only that it "holds onto it for its entire lifespan" which is not clear to me. There's also nothing about the interaction of these pairs with existing mechanisms, like transcription (DNA-->RNA) and translation (RNA-->protein). Could the new new pair increase the space of aminoacids from whi…

It can replicate them, but the XY pairs are just in a plasmid and not in the genome of the bacteria. They were chosen because natural polymerases could use them.

However, there are no corresponding RNA unnatural bases, and there's no tRNA that would recognize that even if there were. So it's going to take a lot more work before you can use these for coding for noncanonical amino acids.

This really is just a proof of concept.

Re: New organisms have been formed using the first ever 6-letter genetic code

#74

Post by 88e282102ae2e5b »

hellbanner wrote: post #23

Confusing to me that "X and Y" are the name of these new letters when X and Y are commonly referred to as sex chromosomes

Well, the actual names of the base pairs they used are dNaM, d5SICS and dTPT3. It doesn't seem to me there are any good choices.

Re: New organisms have been formed using the first ever 6-letter genetic code

#75

Post by zepto »

tstactplsignore wrote: post #65
zepto wrote: post #20

Earlier quoted context omitted.

Software systems are relatively predictable, and built on mathematical models and rules that we designed. Even so, there are still many negative unforeseen consequences of their operation. Biological systems are relatively unpredictable, and based on rules that we didn't design and cannot begin to claim we fully understand. Your analogy therefore strongly predicts negative unforeseen consequences.

Difficult to see how this comment, as common as it is, is anything but unscientific. Biological systems are often highly predictable in many circumstances - in fact "biological predictability" is what accounts for the general success of all modern medicine and agriculture. If the field "cannot begin to claim we don't fully understand" things now, when do we reach the point where we suddenly "know enough to begin to d…

This is nothing but an appeal to authority.

To suggest that accurately gauging the limits of our current knowledge about biological systems is 'anti-scientific' or 'anti-intellectual' goes against everything science stands for, and firmly crosses the line into blind scientism.

It remains absolutely true that we understand the software systems we build far better than we understand the biological systems that we are intervening in.

There is also a straw man in the suggestion that I have said we shouldn't 'do things' until we know more. I never said that.

I simply think that pretending that our understanding of software systems is representative of our understanding of biological systems is a delusion.

Re: New organisms have been formed using the first ever 6-letter genetic code

#76

Post by portent »

klibertp wrote: post #66
portent wrote: post #50

Earlier quoted context omitted.

code can be very simple, and we don't always know what it will do. Simple example: can you tell me if this snippet of (python) code will ever terminate or not? x=0.5 while x 0.7: x=3.59*x*(1-x) print x ... and what if the 3.59 was replaced by a different number - maybe 3.60 ? or 3.84 ?

I think that the argument is that I could know, pretty exactly, not only when (or if) this piece of code terminates, but also how much iterations it's going to take. Sure, it's much easier (in this case) to simply run the thing, experiment with some tweaks a bit and come to some conclusion (like biologists supposedly do?). But I could also go read CPython (assuming CPython) implementation of floating point arithmetic…

What you are saying sounds intuitively true, but the mathematics of Chaos Theory showed that it is not actually the case.

What my code snippet is doing is running a sample of a particular chaotic function that was originally inspired by biology (a simple predator/prey model). Ultimately, what happens is that you just cannot predict how the function will behave - it is chaotic.

Ultimately most complex systems start to show some chaotic behaviour, which basically means that the behaviour of the system cannot be predicted in detail, even if virtually everything is known about the system in advance.

https://en.wikipedia.org/wiki/Logistic_map

Re: New organisms have been formed using the first ever 6-letter genetic code

#77

Post by portent »

joshjje wrote: post #54
portent wrote: post #53

Earlier quoted context omitted.

OK, well we can always say that the heat-death of the universe renders all problems irrelevent, but it's a bit of a cheat in my opinion. The original poster seems to imply that knowing the code means that you can know the behaviour of the system; I do not think that is the case, and my simple (chaotic) example tries to demonstrate this.

If you have the compiled assembly obviously you can say exactly what will happen. I agree with your meaning somewhat though that more often than not many people have no clue, especially with large systems. Its not as bad as your statement though..

Well... the compiled assembly doesn't give you any more information than the code snippet.

The issue is not so much how this code is translated from higher abstraction level to lower abstraction level... the issue is, that this code represents a simple chaotic function (the logistic map). As such, for a simple few lines of code the behaviour is very complex and virtually impossible to predict; for certain values of the controlling number it will (1) halt relatively quickly, (2) never halt, or (3) halt after a very long time... but good luck in distinguishing between cases 2 and 3!

Re: New organisms have been formed using the first ever 6-letter genetic code

#78

Post by portent »

sbmassey wrote: post #56
portent wrote: post #53

Earlier quoted context omitted.

OK, well we can always say that the heat-death of the universe renders all problems irrelevent, but it's a bit of a cheat in my opinion. The original poster seems to imply that knowing the code means that you can know the behaviour of the system; I do not think that is the case, and my simple (chaotic) example tries to demonstrate this.

Well indeed, as per Turing on the Entscheidungsproblem one cannot know what some abstract bit of code does without running it, but one can sometimes put limits on its behaviour - your snippet will never do anything but print out numbers, for example, or something running under seccomp might be prevented from making certain syscalls.

my point is that even running the code doesn't help you answer the question. It runs for a year and doesn't halt... so will it ever halt?

Re: New organisms have been formed using the first ever 6-letter genetic code

#79

Post by eivarv »

_yosefk wrote: post #40
_throwaway1843 wrote: post #8

Star Trek depicted one of the scarier applications of such a technology: There, The Jem'Hadaar are a genetically engineered race of warriors controlled by the Dominion, who exert power over them by being the sole provider of a substance (Ketracel-White) that they need in order to survive: https://en.wikipedia.org/wiki/Dominion_(Star_Trek) http://memory-alpha.wikia.com/wiki/Ketracel-white If my reading of the paper is…

It's good as long self-termination is a nice-to-have feature. If you REALLY want them to self-terminate but you found out that they mutated and can now synthesize X & Y, you're in trouble. Genetically modified organisms are a bit scary, but genetically modified organisms that replicate autonomously are more than a bit scary. As programmers - a profession that managed to spread Shellshock, the dumbest imaginable backd…

    Genetically modified organisms are a bit scary...
Why?

Re: New organisms have been formed using the first ever 6-letter genetic code

#80

Post by maxander »

vivekd wrote: post #72

So will this actually mean anything? Can adding extra letters to an organisms genetic code actually have the capacity to change it's attributes in any meaningful way. Every biological characteristic on the planet seems to have been achieved through using the same 4 molecules, will the addition of more molecules create new characteristics or be useful in any way?

Not really; essentially all DNA "really does" is code for RNA, which in turn codes for amino acid sequences that fold into proteins. As long as the RNA and amino acid libraries are the same, it's just representing the same stuff with a different set of symbols.

In practice, it's probably going to be used as tools for manipulating organisms for experimental purposes, since scientists can do things to the synthetic bases that can't be done to real ones (or that effect natural and synthetic bases differently.)

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