Non-Watson-Crick base pairs that you won't find in the textbooks and Wikipedia

(Continued from previous blog). Yesterday, I found 'officially forbidden' non-Watson-Crick CA and TG base pairs on the website of Nature Scitable. The standard Watson-Crick base pairs are AT and CG. They are in all the textbooks. But, you won't find the non-Watson-Crick base-pairs in the textbooks. Certainly not in this detail. The first figure (a) gives the 4 bases and their rare (tautomeric) forms. They are not in the textbooks. They are apparently in a chemical equilibrium (see arrows). The rare forms are indeed rare, but apparently they do exist. So, we should know about them.

Left: common, Right: rare tautomeric forms of the 4 bases
©Nature Scitable

Standard Watson-Crick base pairs
©Nature Scitable

All 4 bases A, T, C, G have rare forms. But only rare-C and rare-G participate in base pairs, see figure (c). The pairs consists of a common and a rare base. Note that rare-A and rare-T do not participate in rare base pairs:

Rare matching base pairs CA and TG
©Nature Scitable [1]

If this is not confusing enough, on the same webpage Nature shows aberrant base pairing of the bases in their 'normal' form:

Non-Watson-Crick base pairs TG and CA.
©Nature Scitable

My conclusion is that Evolution textbooks and Wikipedia [6] give an incomplete picture of which base pairs are possible in DNA. They do tell about mutation and base pair mismatch, but never show non-Watson-Crick base pairs. I think they should do so. This is an extremely important point: how can you explain mutation to students, if rare base forms and rare base pairs do not exist? Then, show them! If DNA would replicate exclusively on the basis of the standard Watson-Crick base pair rule, then DNA would be copied with 100% reliability eternally. I think, one cannot blame polymerase for copying errors, because polymerase can't enforce chemically impossible base pairing.

Secondly, students get the wrong impression that DNA is a perfect molecule, that bases always follow the Watson-Crick rule, and that DNA is fine-tuned for life. It is an intrinsic property of the bases that they have rare (tautomeric) forms and that they can pair in a non-standard way. 

Hubert Yockey 1992

The question remains: How often do non-Watson-Crick base pairs occur in DNA?  Surprisingly, I found in an aside on page 300 of Hubert Yockey [2] that "the probability that adenine will mispair to cytosine is about 10^-4 x 10^-4 = 10^-8." (AC pair). That is very small. About the CG pair he writes: "...the base selected has a probability of about 10^-4 of being in the imino or enol tautometirc form that leads to mispairing." 

He doesn't do anything with these calculations. However, if I understand him correctly, this means that there is a 1 in 10,000 probability that the C or G base is in the wrong form. This would mean that at every replication round of our genome of 3.2 billion bases, 320,000 C or G bases would mispair. Considering that the human body starting from a zygote experiences about 10 quadrillion (10¹⁵) cell divisions in a lifetime [3] then the unimaginable number of 3,2 x 10²⁰ C or G base mismatches would occur [4]. The proofreading and repair system has the task to repair these mutations...

Anyhow, it is clear by now that DNA as a carrier of hereditary information is far from perfect [5]. A perfectly intelligently designed DNA would be stable, have bases without tautomers, 100% replication fidelity, didn't need proofreading and repair and didn't have accumulation of DNA damage during aging. No cancer and no genetic diseases as a result! Mutations would only be positive and introduced deliberately as an adaptation to changing environmental conditions.

In the next blog I will return to Kondrashov!

Correction

I was informed that on the Dutch wikipedia page Kwantumbiologie tautomerism is mentioned and illustrated with AT base pair mutating in to an AC base pair. On that page one finds interesting references to the English literature! [24 Jan 2023]

Notes

1. This illustration is also present in H F Judson The Eighth Day of Creation, page 434 (not a textbook!)
2. Hubert Yockey (1992) Information theory and molecular biology, hardback Cambridge University Press, page 300. (not an evolution textbook). I have a review of the book on my WDW website.
   
3. Wikipedia article cell division (13 Jan 23), but the meaning of quadrillion differs!
4. In fact 3,2 billion base pairs is the haploid number, but our body cells are diploid so the number should be 6,4 billion! That is the amount of DNA that has to be replicated! And both C and G could be in the wrong tautomeric form, so multiply the number by two.
   
5. Fazale Rana (2022) DNA’s Fine-Tuned Structure Minimizes Harmful Tautomers,  Reasons to Believe. This is a perfect example of a christian/Intelligent designer who claims that DNA’s optimized structure is evidence for the intelligent design of DNA. He does not show any mismatch base pairs such as the Nature Scitable page does. He does not  deny that base tautomers exist, and that tautomeric forms are harmful and trigger mutations, but claims that it could be worse! Read the article, and draw your own conclusion!
6. The Wikipedia article Base pair doesn't mention tautomerism, let alone showing illustrations of base mispairs. The Wikipedia article DNA doesn't mention tautomerism. On the page Tautomer DNA is not mentioned at all, although "nucleobases guanine, thymine, and cytosine" are present, but strangely adenine is absent on that page! Wikipedia is really incomplete in this respect. Later I found the Wikipedia article Non-canonical base pairing, ... but the DNA article does not contain a link to this article. The DNA article however, does contain a paragraph 'Non-canonical bases', but that is not the same as non-canonical base pairing! Wikipedia is like loose sand:  a badly-integrated, disjointed system. There is no supervisor who takes care of the coherence of the whole system. This can be expected from a multi-author encyclopedia. [15 Jan 2023] [23 Jan 2023]