How many natural DNA/RNA bases are now known?

[Jonathan Day]

You have the canonical five (A, G, C, T and U), although I'm seeing articles where it's a little more complicated because there's also a non-standard base of I, although I'm a little fuzzy on when this one appears.

There also seems to be a new base, discovered in viruses, dubbed Z. (Because viruses get involved, I'm looking at both RNA and DNA together.)

https://www.wired.com/story/dna-has-four-bases-some-viruses-swap-in-a-fifth/

I seem to recall reading this one does appear in certain fungi and not just viruses, but can't find the article on that. Besides which, it's not always reliable to go with one-off pieces, especially outside of the scientific journals, which is why I'm not even feeling 100% confident that Z is real.

Besides which, since (according to TFA) "during gene transcription, T-Z was still treated as though it were T-A", it's not even clear if it's reasonable to call Z a new base even if it does exist. That would seem to depend on whether a base is defined chemically or functionally. Although, as TFA suggests Z exists to fool immune systems, do we define function in terms of what it does or how it is seen?

I'm excluding synthetic bases, since there can be an arbitrarily large number of these.

I'm therefore curious as to what geneticists consider to be the bases that arise in nature, without regard to whether they're considered canonical.

[joigus]

Very interesting question. Welcome to SFN.

I'm looking forward to expert answers.

Viruses/viri are peripheral to life. They need hosts, so they came later. But not much later, as they need much less combinatorics than prokaryotes to go by.

There's a certain redundancy in proteins (some proteins can be synthesised from slightly different sequences of nucleic acids).

Maybe some sequences of nucleic acids can use deception? Some kind of reverse-redundancy?: They "look" similar to ribosomes polymerases in the binding site, but they execute completely different functions...

Edited March 7, 2022 by joigus
correction

[Genady]

4 hours ago, joigus said:

There's a certain redundancy in proteins (some proteins can be synthesised from slightly different sequences of nucleic acids).

In fact, there is a lot of redundancy, i.e. the same amino acid being coded by several mRNA codons. There are 64 codons coding for only 20 amino acids:

5 hours ago, Jonathan Day said:

You have the canonical five (A, G, C, T and U), although I'm seeing articles where it's a little more complicated because there's also a non-standard base of I, although I'm a little fuzzy on when this one appears.

There also seems to be a new base, discovered in viruses, dubbed Z. (Because viruses get involved, I'm looking at both RNA and DNA together.)

https://www.wired.com/story/dna-has-four-bases-some-viruses-swap-in-a-fifth/

I seem to recall reading this one does appear in certain fungi and not just viruses, but can't find the article on that. Besides which, it's not always reliable to go with one-off pieces, especially outside of the scientific journals, which is why I'm not even feeling 100% confident that Z is real.

Besides which, since (according to TFA) "during gene transcription, T-Z was still treated as though it were T-A", it's not even clear if it's reasonable to call Z a new base even if it does exist. That would seem to depend on whether a base is defined chemically or functionally. Although, as TFA suggests Z exists to fool immune systems, do we define function in terms of what it does or how it is seen?

I'm excluding synthetic bases, since there can be an arbitrarily large number of these.

I'm therefore curious as to what geneticists consider to be the bases that arise in nature, without regard to whether they're considered canonical.

There seems to be quite a few modified bases occurring naturally, defined chemically. Here is a recent review:

Quote

The four canonical bases that make up genomic DNA are subject to a variety of chemical modifications in living systems. Recent years have witnessed the discovery of various new modified bases and of the enzymes responsible for their processing. Here, we review the range of DNA base modifications currently known and recent advances in chemical methodology that have driven progress in this field, in particular regarding their detection and sequencing. Elucidating the cellular functions of modifications remains an ongoing challenge; we discuss recent contributions to this area before exploring their relevance in medicine.

Natural, modified DNA bases - ScienceDirect

[joigus]

4 hours ago, Genady said:

In fact, there is a lot of redundancy, i.e. the same amino acid being coded by several mRNA codons. There are 64 codons coding for only 20 amino acids:

There seems to be quite a few modified bases occurring naturally, defined chemically. Here is a recent review:

Natural, modified DNA bases - ScienceDirect

You're absolutely right. There's quite a lot of redundancy, including several start/stop codons.  

There may even be redundancy after splicing, as chains like XYZXYZXYZ are essentially the same as YZXYZXYZX, aren't they?

Cyclic symmetries,.... But that's another matter.

Edited March 7, 2022 by joigus
minor addition

[Genady]

1 hour ago, joigus said:

You're absolutely right. There's quite a lot of redundancy, including several start/stop codons.  

There may even be redundancy after splicing, as chains like XYZXYZXYZ are essentially the same as YZXYZXYZX, aren't they?

Cyclic symmetries,.... But that's another matter.

They are not the same. There is no cyclic symmetry. Your example looks like a frameshift mutation, which would lead to a very different peptide chain.

Frameshift mutation - Wikipedia

[joigus]

1 hour ago, Genady said:

They are not the same. There is no cyclic symmetry. Your example looks like a frameshift mutation, which would lead to a very different peptide chain.

Frameshift mutation - Wikipedia

I didn't really mean errors in replication. I meant different versions of splicing. And I did say that. Didn't I? Look, I did:

3 hours ago, joigus said:

There may even be redundancy after splicing,

Splicing is different. It happens after replication. And mind you, making mistakes in replication could be fatal, but making mistakes in trancription, and even more in translation, is quite innocuous in comparison.* Deletion, insertion and frameshift mutation happen before. But you may be right that it wouldn't be completely inconsequential. Do you happen to know how the hypothetical protein I wrote is going to fold?

I'm not sure. That's why I said,

1 hour ago, Genady said:

There may even be redundancy after splicing, [...]

That's the whole point I was trying to make. I don't know. Do you know?

Gosh! I really do have to have my wits around me when you're there...   

But thank you.

* mRNA degrades very quickly.

Edited March 8, 2022 by joigus
jeez

[Genady]

58 minutes ago, joigus said:

I didn't really mean errors in replication. I meant different versions of splicing. And I did say that. Didn't I? Look, I did:

Splicing is different. It happens after replication. And mind you, making mistakes in replication could be fatal, but making mistakes in trancription, and even more in translation, is quite innocuous in comparison.* Deletion, insertion and frameshift mutation happen before. But you may be right that it wouldn't be completely inconsequential. Do you happen to know how the hypothetical protein I wrote is going to fold?

I'm not sure. That's why I said,

That's the whole point I was trying to make. I don't know. Do you know?

Gosh! I really do have to have my wits around me when you're there...   

But thank you.

* mRNA degrades very quickly.

Yes, you did say splicing. It is my fault that I've missed it. I'm sorry.

In my misunderstanding, I thought that X,Y,Z in your strings stand for arbitrary nucleotide bases. Now, after you've mentioned "hypothetical protein", I think they stand for arbitrary amino acids. Is this correct?

Are we talking about mRNA splicing that occur after transcription and before translation? When introns get excised and exons get connected? I don't know about any redundancy associated with this splicing. I do know that alternative splicing is used to make different polypeptides from the same DNA sequence. This is somewhat opposite to redundancy.

[joigus]

20 minutes ago, Genady said:

In my misunderstanding, I thought that X,Y,Z in your strings stand for arbitrary nucleotide bases. Now, after you've mentioned "hypothetical protein", I think they stand for arbitrary amino acids. Is this correct?

Yes, I'm sorry too, because now I realise I wasn't clear. I meant there may be even more redundancies further down the line replication --> transcription --> translation.

And by XYZ... I meant the protein, that is, the sequence of aminoacids. Suppose the nucleotide sequence codes for a particular protein, instead of a transcription factor, or a protein that needs to fold in a very precise way at the level of beta structure, etc., like, eg. hemoglobin. Just a simple alpha-structure completely boring structural chain. So in that case there would be even more redundancy at the "production line" level, so to speak. For some proteins it could be the case that cutting (splicing) here or there doesn't really make that much of a difference.

By XYZ I should have specified valine-glycine-whatever. In some proteins the Y aminoacid (say it's hydrophobic) could be just fine if you simply replace it by another hydrophobic aminoacid and everything would be OK structurally. Even if it's a transcription factor, it could be the case that it binds just a little bit less efficiently by changing one aminoacid, so your equilibrium constant would be displaced just the slightest bit to the left...

So you're right. I don't disagree with you. There would be the redundancies that you point out, and maybe even more. In fact I understand redundancies of this kind are essential for there being a possibility of evolution to be so "malleable."

It's an interesting discussion, but we're getting off the track...