Four new DNA letters double life’s alphabet

Probably moreso now than ever with the synchronized ideation from Internet news and social media.

Which mountain was it?

are you sure it wasn't Steven Brenner or Syndey Brenner? Or maybe Seymore Benzer? I always get them confused.

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_

See also: https://en.wikipedia.org/wiki/Tetrachromacy#Humans

Although I have my doubts that this is what the mystics you're referring to are talking about.

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).

To the color thing, I've met more than one person who has taken LSD and seen new colors. Rational and level-headed people otherwise.

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.

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.

You may be interested in https://en.m.wikipedia.org/wiki/Impossible_color

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".

For sound we do much better.

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.

Just as a sidenote: In Computer Graphics (and according to Grassmann's law) colour is a three dimensional quantity.

>The whole collection deserves a content warning

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.

> 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)

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.

IIRC, optimal information density is achieved by an alphabet the size of Euler's number [1]. So trinary might actually be theoretically optimal since we have to be discrete.

But there are pragmatic considerations to consider that make trinary difficult. Since most of computation currently happens with voltage, that's a one-dimensional quantity that we would have to divide into 3 levels to discriminate "bits". This requires more sensitivity and precision than merely two levels. (Edit: although maybe not, some historical computers were trinaryband reportedly more efficient; time will tell I suppose).

It would be easier to achieve trinary if we had two axes with which to encode, but that intrinsically yields quaternary; maybe that's how DNA operates.

[1] It is via radix economy: https://en.wikipedia.org/wiki/Radix_economy#Radix_economy_of...

There are 20 aminoacids encoded in the DNA, and you need an "stop" code (the "start" code is reused when it is in the middle).

There are some tricks to transform the 20 aminoacids in other aminoacids after they are in the proteins, so that increase the number of used aminoacids a little https://en.wikipedia.org/wiki/Non-proteinogenic_amino_acids And there are small variations of the genetic code that include other aminoacids https://en.wikipedia.org/wiki/Genetic_code#Alternative_genet.... So the total number of aminoacids used in the wild is approximately 30.

With 4 bases and 3 bases per codon, you can encode up to 64, so there is some redundancy and room for a few new aminoacids.

You don't want too much redundancy, because you have to synthetize the tRNA. And in principle you need a tRNA for each possible codon, so you want to minimize the number of codons. (Actually, the genetic code has some patters and instead of 63 tRNA the cells have at most 41 tRNA. https://en.wikipedia.org/wiki/Transfer_RNA

I guess that increasing the number of bases makes it more easy to make mistakes, and more difficult for the enzymes to distinguish them.

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.

>Are there new proteins this lets them make?

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...

Edit: spelling

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.

This is essentially one of the arguments made in The Equations of Life: How Physics Shapes Evolution by Charles S. Cockell

"In March 2015, NASA scientists reported that, for the first time, complex organic compounds found in DNA and RNA, including uracil, cytosine and thymine, have been formed in the laboratory under outer space conditions, using starting chemicals, such as pyrimidine, found in meteorites. Pyrimidine and polycyclic aromatic hydrocarbons (PAHs) may have been formed in red giants or in interstellar dust and gas clouds, according to the scientists."

https://en.wikipedia.org/wiki/Meteorite#Meteorite_chemistry, which cites https://www.nasa.gov/content/nasa-ames-reproduces-the-buildi...

Start by getting one with a 12-"letter" name and see how that works !!

No one is talking about "throwing out billions of years of biochemistry". Rather, by changing a small part of biochemistry we will be better able to understand it. Not all research is about making something better.

Artificial bases might help us understand why live evolved the way it did. Maybe there is an interaction between the bases and the way DNA folds? Or were ACTG just an accident?

Artificial bases might be useful as part of other techniques, perhaps for tagging DNA sequences. Maybe they can one day be used to disrupt or alter certain biological processes.

I am not a biologists, so I have no idea if that makes any sense, but the research is interesting.

Mankind has always striven to understand his universe. You don't really understand something until you can tear it down and rebuild it in a hundred different ways.

There are lots of reasons. For one, expanding the genetic code would allow new and interesting structures in RNAs, would allow massive expansion of amino acid coding sets, different evolution paths based on codon usage, etc. Generally in synthetic biology we want to build new systems from scratch, and these base pairs are a wonderful step in humanity defining life instead of life defining humanity.

There is productive research into using DNA as a data storage medium. I could see this being used to either increase data density or as an error-correction mechanism.