niiicholas
Posts: 319
Joined: May 2002
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Hey Nelson, welcome to AE.
Unfortunately I don't have a week to really wrap my head around the cytosine deamination issue. However I guess I was the "provoker" of the Mike Gene article you cite in that I posted the article "Confounded cytosine" which he is reacting to.
So if debate of this topic begins (by people other than me), let's start by accumulating the relevant links etc. on this thread and then go from there.
Here is an ARN post with some discussion, including some quotations from the article, with the hopes of laying out what Poole et al. were arguing. Unfortunately this argument is embedded in a more complex discussion of various topics related to RNAworld and the origin of the genetic code which makes simple quoting difficult and I think confused subsequent discussion as it is not at all clear that the IDists involved accept or reject either RNAworld or a gradual origin of the genetic code and DNA.
ARN thread
Begin re-post of summary of Poole et al.:
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I do believe I provoked this particular MG essay when I posted this reference on ISCID:
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Nat Rev Mol Cell Biol 2001 Feb;2(2):147-51
Confounded cytosine! Tinkering and the evolution of DNA.
Poole A, Penny D, Sjoberg BM.
Institute of Molecular BioSciences, PO Box 11222, Massey University, Palmerston North, New Zealand. a.m.poole@massey.ac.nz
Early in the history of DNA, thymine replaced uracil, thus solving a short-term problem for storing genetic information--mutation of cytosine to uracil through deamination. Any engineer would have replaced cytosine, but evolution is a tinkerer not an engineer. By keeping cytosine and replacing uracil the problem was never eliminated, returning once again with the advent of DNA methylation.
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Here is the direct link although you may need subscription access.
There argument is complex but here is the gist:
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The origin of DNA is a fundamental question in evolution. Early on, DNA replaced RNA, reflecting the superior information-storage capacity of DNA1, 2. Modern biochemical pathways provide an insight into this transition, as do RNA and uracil-DNA (U-DNA) viruses2, 3, suggesting that the replacement took place in two steps (Figs 1, 2a): replacement of ribose with deoxyribose, then replacement of uracil (U) with thymine (T)4. The first step was probably very complex, and has recently been reviewed elsewhere2, 5. Here we look at the second (UT) replacement, which is emerging as another example of why evolution is best viewed as a tinkerer, not as an engineer with an eye for 'good' design (Box 1).
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Central to the story is cytosine ©, which readily deaminates to form U. This turns CG pairs into UG mispairs, and is an ongoing process in DNA6, 7 (Fig. 2b). Without repair, replication of a UG mispair would give one UA pair (which is read as a TA pair) and one CG pair. All organisms carry the machinery for repair of C deaminations — uracil-N-glycosylase (UNG), which recognizes and removes any U that it detects, leaving an abasic site. This is patched up by base-excision repair8, 9 (Fig. 3), which creates a gap in the DNA opposite G. DNA polymerase then fills the gap with dC, thus repairing the mutation. Occasionally, U (from dUTP) is incorporated opposite A, so both UG and UA pairs turn up in DNA. The UNG recognizes and removes U arising from either C deamination or misincorporation, allowing DNA to be faithfully repaired10-12.
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Before T was a constituent of DNA, it would have been harder to detect C deaminations, because U was a bona fide constituent of early DNA at UA pairs. It is widely accepted that U-->T replacement solved this problem because it allowed any U arising by C deamination to be detected unambiguously.
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François Jacob14 has likened evolution to "tinkering". In contrast to an engineer, who works by design, obtaining all the necessary materials needed for construction of a prototype and finally testing it before putting it to work, a tinkerer makes use of whatever is at hand. This means that the result, although functional, is often far from perfect. A consequence of this modus operandi is that if something works in the short term it will be used, even if a better alternative is conceivable. New innovations cannot arise only to become useful when a subsequent function evolves, because there is no selection to maintain such innovations before they become useful.
Recent progress on the biochemistry of U removal reveals an unexpected diversity of reactions catalysed by members of the uracil-DNA glycosylase family (even though they all share a common origin), and allows the U-->T conundrum to be resolved. New data15 on a closely related phenomenon — the repair of deaminated 5-methylcytosine (5-meC, which deaminates to T, resulting in a TG mismatch; Fig. 2b) — highlights the usefulness of the tinkering analogy for evolution. The problems solved by replacing U with T resurfaced once again when C methylation became a feature of the genome, with a member of the U-DNA glycosylase family being recruited to repair 5-meCT deaminations.
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The trouble with T
As eukaryotic genomes became more complex, additional mechanisms of gene regulation developed. One such mechanism is DNA methylation, where a methyl group is added to position 5 on the cytosine ring, forming 5-meC (Ref. 15). The ability to regulate genes by C methylation would have been beneficial, but it came with a catch: 5-meC deaminates to T at a rate 2–4-fold higher than C deaminates to U (Fig. 2)21, meaning that a new form of mismatch became a problem. In eukaryotes, thymine-DNA glycosylase (TDG), which is evolutionarily related to UNG and MUG, repairs TG mismatches arising from deamination of 5-meC (Refs 17,25).
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Replacing U with T provided a means by which to fine-tune repair of C-->U deaminations, but the problem of C deamination was never eliminated — it re-emerged in the form of 5-meC deamination. Tinkering also makes sense of the evolution of the 5-meC apparatus, which subsequently drove the recruitment of the U-excision apparatus into T excision because of the 'unforeseen' side effect of 5-meCT deamination. All this could have been avoided simply by eliminating C early in the evolution of the genetic material — but how boring life would be if evolution worked by engineering.
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