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My question arose from this article on Wikipedia on the GC-skew in bacterial genomes: https://en.wikipedia.org/wiki/GC_skew As far as I understood, the lagging strand (the template strand), during replication, is more often single stranded than the leading strand (template), so it is more prone to mutations like deamination. Therefore, on the lagging strand (here, the one being the template to the strand formed by Okazaki fragments), one should expect more Ts and fewer Cs. Conversely, the strand synthesised by Okazaki fragments should have an enrichment of As and a depletion of Gs. Why does the Wikipedia article mention a increase in the ratio of (G+T)/(C+A)? I would expect an increase in the ratio of (T)/(C). I don't get the link with Gs and As.

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  • $\begingroup$ Please cite as a quotation the actual sentence(s) that mentions the (G+T)/(C+A) ratio. I cannot find it and without it your question is unclear. The article you mention is very dense — I have not been able to understand it merely by skimming it — and the impression I get is that it is not mainstream, but represents opinion rather than fact. You may be unaware that anyone can write articles for Wikipedia — the only quality control is readers.) I think your question would be better as “What causes the GC skew between strands” and cite this article as one explanation (which you don’t understand). $\endgroup$ – David Dec 29 '17 at 11:30
  • $\begingroup$ I'm voting to close this question as off-topic because the purpose of this list is to answer questions about biology, not to clarify the reasoning of scientific authors. In this case rephrasing the question so that it is focused on the possible causes of GC skew would be valid but not one in which the answer is assumed in the question. $\endgroup$ – David Dec 30 '17 at 15:42
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I think you are referring to this sentence from your wikipedia link:

There is a richness of guanine over cytosine and thymine over adenine in the leading strand and vice versa for the lagging strand.

Note that this is not saying (G+T) > (C+A). It is instead saying (G)>(C) and (T)>(A). I think that those are not the same as saying (G+T) > (C+A), though that is also true, probably?

So I think that there is no contradiction there- it is just, as you say, more Ts (relative to expected equality with As) and fewer Cs (relative to expected equality with Gs).

If I understand correctly, the importance of the GC skew, and the reason that it is interesting, is that it acts as a deviation from Chargaff's parity rules (as explained in the article). These rules state that for any given hunk of DNA, (G)~(C) and (T)~(A), which is the expected composition for (for example) double-stranded DNA, because of base-pairing.

Edit: for more information on Chargaff's rules, see this other question which I have (through pure coincidence) answered here. Note that the second parity "rule" is a statistical phenomenon, rather than a logically required rule. The wikipedia page on Chargaff's rules is also informative.

Hope that helps.

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  • $\begingroup$ I don't understand the second parity rule of Chargaff: 'In other words, in each DNA strand the frequency of occurrence of T is equal to A and the frequency of occurrence of G is equal to C because the substitution rate is presumably equal.' Why should the numbers of Cs and Gs be equal on one strand? "It is instead saying (G)>(C) and (T)>(A)." Is that true in a single strand? In the template strand of the lagging strand? $\endgroup$ – charlesdarwin Dec 28 '17 at 0:33
  • $\begingroup$ see edit to answer linking to answer to question about parity rule. $\endgroup$ – Maximilian Press Dec 29 '17 at 1:13
  • $\begingroup$ Both of Chargaff’s rules were based on observation rather than logic. Indeed, it was because he was unable to rationalize his first ‘rule’ that Watson and Crick got the Nobel Prize for the structure of DNA and not him. It is also the reason to regard these ‘rules’ as no more than history. $\endgroup$ – David Dec 29 '17 at 11:10
  • $\begingroup$ @David is correct about Chargaff making descriptive observations, as is also stated in the linked answer. I'm not sure that I understand why these rules should be purely regarded as history when they remain a highly accurate (though merely statistical) portrait of DNA composition. I think there are a lot of arguments about why that Nobel happened the way it did, I'm not sure that I agree with that characterization but going into it would be rather off-topic here. $\endgroup$ – Maximilian Press Dec 30 '17 at 0:25
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    $\begingroup$ Let me put it differently. I dislike the word ‘rule’ in this context because it implies some fundamental understood physical ‘law‘, and I dislike the two being associated as they are distinct in time and importance. A better word would be ‘observations’. The first set of observations were made on a limited subset of genomes and were not understood until the double-helical nature of DNA was established. They then became history — observations that were now explicable. The second set of observations are distinct and obscure. Associating them with the first set as another ‘rule‘ is unjustified. $\endgroup$ – David Dec 30 '17 at 15:37

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