Tangentially related story - Steve benner was the researcher whose work inspired me to go to grad school; during the 2017 eclipse I travelled with a friend to a remote mountain in the path if totality to observe it; on the way down I ran into Steve benner (there were about 6-8 people on the mountain that day), and was left wondering if sometimes serendipitous meetings are instead the result of similar deductive processes in activity selection and not serendipity at all.
This reminds me a bit of how mystics often claim to have seen colors not seen in nature. Crazy, weird, sure, but when you actually look at the rod and cone structure that gives rise to color, there's no reason to think that more of these might not exist, and indeed some animals have different receptors, famously, the mantis shrimp has 12. Color occupies that weird junction between the subjective and objective, so we don't really have a way of working out what the subjective experience of new colors would actually be.
Why this reminds me of color isn't so much the weird part, but the fact that color is a continuous surface. What would adding new colors do to the color space? Does the space remain two-dimensional or do new colors start blending a third dimension into the topology? I wish those mystics had access to spectrometers in Heaven.
More critically, the mantis shrimp doesn’t have opponency.
In humans—-and most other animals—-the visual system represents color[0] using a relative system: is something redder than it is green? Bluer than it is yellow? To create this, neurons receive excitatory input from (e.g.) a red cone and inhibitory input from nearby green cones. This representation makes sense, given the cones’ spectral sensitivity, but it also makes some colors “impossible”. Since each color is essentially a point along these two axes, something can’t be blue and yellow at the same time, reddish green, or even some shades of “hyper-green”[1,2].
The mantis shrimp, near as we can tell, doesn’t have this sort of representation. The anatomical pathways don’t seem to be there, and some behavioral work with trained(!) mantis shrimp also suggests that they have independent color channels, and, as a result, their color sensitivity is actually not amazing. Interestingly, they may do something to “fake” color opponency: different receptor types are in different parts of the eye, and the shrimp ‘drags’ its eye across the scene to produce a sort of temporal context.
That’s more than you probably wanted to know but...shrimp are neat.
[0] To a first approximation, anyway.
[1] There is a place called Reddish Green, which I assume is not invisible, but I’ve never been to Stockport, England.
[2] More seriously, there are some tricks you can play to (briefly) perceive some of these impossible colors. The general approach is that you stare at something of one color, then quickly switch to looking at something of the opponent color. This “fatigues” (adapts) cells that signal the first color, so they provide less inhibitory input in response to the second color.
Some females (due to the XX chromosome setup) are born with red cone receptors that are sensitive to sufficiently different ranges in the wavelength spectrum that they are in effect tetrachromats. I particularly remember reading somewhere that when asked how they experienced the world they had reported to often notice bad color matchings in the way people dress, I suppose much like it can sometimes be apparent that someone is red-green color blind by this same dressing queue.
But a different kind of rod altogether, firing off some completely different signal, who knows what the experience would be like. Psychophysics is a mysterious junction indeed.
"It was octarine, the colour of magic. It was alive and glowing and vibrant and it was the undisputed pigment of the imagination, because wherever it appeared it was a sign that mere matter was a servant of the powers of the magical mind. It was enchantment itself.
But Rincewind always thought it looked a sort of greenish-purple." - Terry Pratchett, _The Color of Magic_
It's not clear what the relation between sensory input and the experience generated actually is. For a crude analogy, one might think the client sending a certain JSON structure is what leads to a certain database update, but the server can alter that structure in arbitrary ways. You can also get database updates without sending any JSON at all. We should be looking at the server, not the client, to figure out how the database updates work. Similarly, a brain can probably generate arbitrary experiences in qualia-space (although probably dependent on the neural structure to do so).
Every sensory perception is just as subjective, for example sound also "occupies that weird junction between the subjective and objective" in that is how animals interpret the vibration of airwaves despite being thousand of other possible ways to interpret such vibrations; same with touch, smell, etc.
Imagine you're looking at wall with 3 colored circles, red green blue - something happens and you can now see a fourth circle that wasn't there before.
You've experienced it already... by shining a black light on ultraviolet pigment.
What makes it mystical is that there is color as a physical phenomenon (which relies on rods and cones etc.), and color as a subjective experience which occurs entirely in the thought space of consciousness. Typically the mapping between the two is relatively standard and static, but imagine a situation in which your consciousness registers something which has not correlate in the physical world. That doesn't make it any less real to your consciousness.
> This reminds me a bit of how mystics often claim to have seen colors not seen in nature.
There is infinitely more wavelength info even in the visible light of nature than the crude three dimensional mapping our eyes can present to our brains.
One simple example: We can't distinguish green light from mixed blue and yellow light.
So my point, which I know I'm annoying slow to get to, is that we're nowhere near seeing "the colors of nature".
At a meditation retreat we did some form of “shanmukhi mudra” and I definitely saw some of the most intense colors of my life. I think the combination of sensory deprivation and pressure on the eyelids is what did the trick.
Greg Egan wrote a good short story with a related premise: a pathologist investigating evidence discovers the DNA is formed of novel bases. It's called 'The Moat' and is published in the collection 'Axiomatic'.
The whole collection deserves a content warning, but if you enjoy Black Mirror then you'll enjoy these.
Really really interesting work. I have so many questions. I wonder if the new letters change the molecular structure overall. Do these molecules bend and twist like vanilla DNA does? Will they wrap around histones? Can any of the new letters be methylated?
I’m also glad the article stressed the importance of polymerase. For the uninitiated, if this molecule cannot be replicated with polymerase, then it severely constrains its applicability. Most research labs do not synthesize their own DNA - they replicate it in cells or with PCR.
> I wonder if the new letters change the molecular structure overall. Do these molecules bend and twist like vanilla DNA does?
Expanded genetic systems are most likely to work with natural enzymes if the added nucleotides pair with geometries that are similar to those displayed by standard duplex DNA. Here, we present crystal structures of 16-mer duplexes showing this to be the case with two nonstandard nucleobases (Z and P)
Z has an amine group where the methylation would go on cytosine, and P has a ketone group instead of the amine group where the methylation would go on adenine, so presumably not, or at least not in the same way.
Before I knew much about transistors etc, I used to wonder why only 2 logic levels (0 and 1) are generally used in computers. I know there are some exceptions but it turns out binary works best with the hardware we have available. I'm guessing that four logic levels works best with ribosomes and all the other cellular machinery. Or maybe it's hard to have codons longer than 3, so the number of DNA bases is set by the number of required amino acids to sustain life?
This is a perennially recurring article. Seems like every few years someone is adding base pairs to DNA. The first one I can recall used the Greek letters kappa and chi for the novel base pair. I thought it was cool and exciting at the time, which was probably around 1992. They keep coming up with new ones, and reviving the "6 letter DNA alphabet" articles.
2-amino-8-(2-thienyl)purine and pyridine-2-one
7-(2-thienyl)imidazo[4,5-b]pyridine and pyrrole-2-carbaldehyde
7-(2-thienyl)imidazo[4,5-b]pyridine and 4-[3-(6-aminohexanamido)-1-propynyl]-2-nitropyrrole
2-(2-Deoxy-β-D-erythro-pentofuranosyl)-6-methyl-1(2H)-isoquinolinethione and (1R)-1,4-Anhydro-2-deoxy-1-(3-methoxy-2-naphthyl)-D-erythro-pentitol
These all work fine when copying DNA sequences using existing cellular mechanisms and PCR. As far as I know, it remains to be seen whether they can encode for proteins.
RNA transcription is complicated by "wobble pairs" with uracil, inosine, and uridine variants, occurring in RNA, with the four bases present in DNA, and with each other. There isn't a 1-to-1 correspondence from DNA base to RNA base. It may be that our DNA uses only the four specific bases guanine, cytosine, adenine, and thymine because wobble pairings provided additional mutation resistance, or offered additional structural options for transcribed proteins.
To make new proteins, you have to create new ribosomes, as it's they who interpret the RNA codons to stitch amino acids together. Bootstrapping a new ribosome is several magnitudes harder than constructing a synthetic DNA/RNA.
Actually, you don't even need new DNA letter to do that. DNA codons can encode 64 different amino acids (63, as one codon must encode the end of sequence), but only 20 amino acids are actually used.
Adding another amino acid is theoretically possible, but this would require rewriting the whole DNA to reencode, say leucine from CTG to another codon to assign CTG to some other acid.
I think for now we are still a ways off from this being interesting at the protein level. I would think you would need new tRNAs to recognize the new bases in-order to really utilize them at a protein level, and those tRNAs would need to bind to different amino acids than we currently have for there to be any new protein function that we can't already accomplish with ATCG.
That being said, you can still do a lot of interesting stuff with nucleic acids like DNA and RNA, more and more research these days show they can do more than just encode information for proteins.
IIRC RNA is made up mostly of the same nucleic acids as DNA. T (something something) is replaced by Uracil. The main difference is that DNA is double stranded whereas RNA is single stranded. Since mRNA uses three acids to represent one of the amino acids that make up the proteins it encodes, and there is a finite amount of amino acids, this means no new proteins are encoded if you add more "letters" to DNA/RNA.
Possibly the RNA could have some secondary function in the folding of the protein or as a complex inside it...
DNA does more than code for proteins, but in terms of proteins, 3-letter DNA codons already provide for 64 possibilities, and there are only 20 amino acids.
That number hasn't been subject to evolutionary selection for as long as there have been cells since evolution doesn't have any way to change it. So there's no reason to think it's optimal.
Well, I'm sure that if you evolved life for long enough it might find a way to switch bases. But this looks far harder than the sorts of changes that take a billion years, like photosynthesis or eukaryotes. So I wouldn't expect it to happen before the Sun boils off life on Earth in another billion.
Pretty interesting. I wonder if bio-hackers from the future will tinker for fun and exchange very large steganographic 'files' that, if read in a certain order, produced the complementary DNA (cDNA) [0] of a patented organism.
That opens the door to a genetic signature for man made and modified creatures in a not much far away future. Would be important to clear biological invasions or "tainted" species if you can check for it.
This is pretty cool! I wonder if there is so some limit in how many pairs can be added. I’d imagine as we try to store more information in a system like this we’ll keep adding synthetic pairs.
[+] [-] dnautics|7 years ago|reply
[+] [-] jcims|7 years ago|reply
[+] [-] socketnaut|7 years ago|reply
[+] [-] dekhn|7 years ago|reply
[+] [-] vinceguidry|7 years ago|reply
Why this reminds me of color isn't so much the weird part, but the fact that color is a continuous surface. What would adding new colors do to the color space? Does the space remain two-dimensional or do new colors start blending a third dimension into the topology? I wish those mystics had access to spectrometers in Heaven.
[+] [-] mattkrause|7 years ago|reply
In humans—-and most other animals—-the visual system represents color[0] using a relative system: is something redder than it is green? Bluer than it is yellow? To create this, neurons receive excitatory input from (e.g.) a red cone and inhibitory input from nearby green cones. This representation makes sense, given the cones’ spectral sensitivity, but it also makes some colors “impossible”. Since each color is essentially a point along these two axes, something can’t be blue and yellow at the same time, reddish green, or even some shades of “hyper-green”[1,2].
The mantis shrimp, near as we can tell, doesn’t have this sort of representation. The anatomical pathways don’t seem to be there, and some behavioral work with trained(!) mantis shrimp also suggests that they have independent color channels, and, as a result, their color sensitivity is actually not amazing. Interestingly, they may do something to “fake” color opponency: different receptor types are in different parts of the eye, and the shrimp ‘drags’ its eye across the scene to produce a sort of temporal context.
That’s more than you probably wanted to know but...shrimp are neat.
[0] To a first approximation, anyway.
[1] There is a place called Reddish Green, which I assume is not invisible, but I’ve never been to Stockport, England.
[2] More seriously, there are some tricks you can play to (briefly) perceive some of these impossible colors. The general approach is that you stare at something of one color, then quickly switch to looking at something of the opponent color. This “fatigues” (adapts) cells that signal the first color, so they provide less inhibitory input in response to the second color.
[+] [-] arketyp|7 years ago|reply
But a different kind of rod altogether, firing off some completely different signal, who knows what the experience would be like. Psychophysics is a mysterious junction indeed.
[+] [-] lostphilosopher|7 years ago|reply
[+] [-] pmjordan|7 years ago|reply
Although I have my doubts that this is what the mystics you're referring to are talking about.
[+] [-] ZeroFries|7 years ago|reply
[+] [-] c3534l|7 years ago|reply
[+] [-] mattigames|7 years ago|reply
[+] [-] zepolen|7 years ago|reply
You've experienced it already... by shining a black light on ultraviolet pigment.
It's the same principle behind color blind test patterns: https://cdna.allaboutvision.com/i/eye-exam-2017/color-blind-...
A color blind person sees one color - a normal vision person sees two.
[+] [-] dooglius|7 years ago|reply
[+] [-] JackFr|7 years ago|reply
[+] [-] BurningFrog|7 years ago|reply
There is infinitely more wavelength info even in the visible light of nature than the crude three dimensional mapping our eyes can present to our brains.
One simple example: We can't distinguish green light from mixed blue and yellow light.
So my point, which I know I'm annoying slow to get to, is that we're nowhere near seeing "the colors of nature".
For sound we do much better.
[+] [-] wes-k|7 years ago|reply
[+] [-] wittenator|7 years ago|reply
[+] [-] MatthewWilkes|7 years ago|reply
The whole collection deserves a content warning, but if you enjoy Black Mirror then you'll enjoy these.
[+] [-] simias|7 years ago|reply
I'm not sure what you mean by that. Who needs to be warned and of what?
Thank you for the recommendation though, there's never too much sci-fi to read as far as I'm concerned.
[+] [-] biophysboy|7 years ago|reply
I’m also glad the article stressed the importance of polymerase. For the uninitiated, if this molecule cannot be replicated with polymerase, then it severely constrains its applicability. Most research labs do not synthesize their own DNA - they replicate it in cells or with PCR.
[+] [-] twic|7 years ago|reply
Expanded genetic systems are most likely to work with natural enzymes if the added nucleotides pair with geometries that are similar to those displayed by standard duplex DNA. Here, we present crystal structures of 16-mer duplexes showing this to be the case with two nonstandard nucleobases (Z and P)
https://www.ncbi.nlm.nih.gov/pubmed/25961938
> Can any of the new letters be methylated?
Z has an amine group where the methylation would go on cytosine, and P has a ketone group instead of the amine group where the methylation would go on adenine, so presumably not, or at least not in the same way.
[+] [-] foobarbecue|7 years ago|reply
[+] [-] logfromblammo|7 years ago|reply
2-amino-8-(2-thienyl)purine and pyridine-2-one
7-(2-thienyl)imidazo[4,5-b]pyridine and pyrrole-2-carbaldehyde
7-(2-thienyl)imidazo[4,5-b]pyridine and 4-[3-(6-aminohexanamido)-1-propynyl]-2-nitropyrrole
2-(2-Deoxy-β-D-erythro-pentofuranosyl)-6-methyl-1(2H)-isoquinolinethione and (1R)-1,4-Anhydro-2-deoxy-1-(3-methoxy-2-naphthyl)-D-erythro-pentitol
These all work fine when copying DNA sequences using existing cellular mechanisms and PCR. As far as I know, it remains to be seen whether they can encode for proteins.
RNA transcription is complicated by "wobble pairs" with uracil, inosine, and uridine variants, occurring in RNA, with the four bases present in DNA, and with each other. There isn't a 1-to-1 correspondence from DNA base to RNA base. It may be that our DNA uses only the four specific bases guanine, cytosine, adenine, and thymine because wobble pairings provided additional mutation resistance, or offered additional structural options for transcribed proteins.
[+] [-] mrfusion|7 years ago|reply
[+] [-] orthoxerox|7 years ago|reply
Actually, you don't even need new DNA letter to do that. DNA codons can encode 64 different amino acids (63, as one codon must encode the end of sequence), but only 20 amino acids are actually used.
Adding another amino acid is theoretically possible, but this would require rewriting the whole DNA to reencode, say leucine from CTG to another codon to assign CTG to some other acid.
[+] [-] el_cujo|7 years ago|reply
I think for now we are still a ways off from this being interesting at the protein level. I would think you would need new tRNAs to recognize the new bases in-order to really utilize them at a protein level, and those tRNAs would need to bind to different amino acids than we currently have for there to be any new protein function that we can't already accomplish with ATCG.
That being said, you can still do a lot of interesting stuff with nucleic acids like DNA and RNA, more and more research these days show they can do more than just encode information for proteins.
[+] [-] archevel|7 years ago|reply
Possibly the RNA could have some secondary function in the folding of the protein or as a complex inside it...
Edit: spelling
[+] [-] antirez|7 years ago|reply
[+] [-] dnhz|7 years ago|reply
[+] [-] Symmetry|7 years ago|reply
Well, I'm sure that if you evolved life for long enough it might find a way to switch bases. But this looks far harder than the sorts of changes that take a billion years, like photosynthesis or eukaryotes. So I wouldn't expect it to happen before the Sun boils off life on Earth in another billion.
[+] [-] joshuahedlund|7 years ago|reply
[+] [-] RobertoG|7 years ago|reply
An interesting corollary would be that, if we find them outside Earth, then, probably, they didn't evolve on Earth
[+] [-] rolandog|7 years ago|reply
[0] http://sitn.hms.harvard.edu/flash/2015/the-patent-landscape-...
[+] [-] pvaldes|7 years ago|reply
[+] [-] duncan-donuts|7 years ago|reply
[+] [-] pavlov|7 years ago|reply
[+] [-] vkaku|7 years ago|reply
6P3 vs 4P3;
[+] [-] qwerty456127|7 years ago|reply
[+] [-] Crystalin|7 years ago|reply
[+] [-] yread|7 years ago|reply
[+] [-] hoseja|7 years ago|reply
[+] [-] pytyper2|7 years ago|reply
[+] [-] swamp40|7 years ago|reply
[+] [-] beckerdo|7 years ago|reply