Why thymine instead of uracil?

 

by Piter Kehoma Boll | September 29, 2012 · 12:05 pm

About a year ago, while I was in my class of Techniques of Molecular Diagnosis, an interesting doubt sprouted: why does DNA use thymine instead of uracil as RNA does?

I hope everybody reading this knows about nucleic acids and the difference between DNA and RNA. As a very quick review:

RNA (ribonucleic acid) is a polymer made of ribonucleotides, compound molecules made of three parts, or smaller molecules: a nitrogenous base (adenine, uracil, cytosine or guanine), a ribose sugar and a phosphate group.

DNA (deoxyribonucleic acid) is similar, but instead of uracil it has thymine, and instead of a ribose sugar is has a deoxyribose, so that it is made of deoxyribonucleotides. Another difference is that DNA is a double chain twisted helicoidally, where two nitrogenous bases (each from one of the chains) are connected. Adenine is always connected to thymine and cytosine always to guanine, so that one chain is always dependent on the other.

Currently it’s highly accepted that RNA was the first nucleic acid to exist and that DNA evolved from it, so the changes in the sugar and one of the nitrogenous bases must have some advantage.

To understand that, let’s take a look at the structure of the uracil:

Uracil

The only difference between it and thymine is the presence of a methyl group at the last one:

Thymine

In fact, thymine is also called 5-methyluracil. But let’s go to the explanation:

While nucleotides are synthesized, the nucleotide-monophosphates (NMPs), i.e., the set nitrogenous base + sugar + phosphate is dehydroxylated, creating 2’-deoxy-nucleotide-monophosphate (dNMPs), i.e., GMP, AMP, CMP and UMP (for guanine, adenine, cytosine and uracil) are changed to dGMP, dAMP, dCMP and dUMP.

This modification by dehydroxylation has been shown to make the phosphodiester bonds (the bonds of phosphates on the sugar) less susceptible to hydrolysis and damage by UV radiation. It assures that a DNA molecule will not be as easy to be broken as an RNA molecule, which is very useful since DNA carries all the information to build up the organism.

After the dehydroxilation of the nucleotide-monophosphates, the next step, catalyzed by folic acid, add a methyl group to the uracil to form a thymine, so turning dUMP into dTMP.

There are many explanations for that:

1. Despite uracil’s tendency to pair with adenine, it can also pair with any other base, including itself. By adding a methyl group (which is hydrophobic) and turning it into thymine, its position is reorganized in the double-helix, not allowing those wrong pairings to happen.

2. Cytosine can deaminate to produce uracil. You can see in the picture below that the only difference between them is the change from an O in uracil to an NH2 in cytosine. The problem is that, if uracil were a component of DNA, the repair systems would not be able to distinguish original uracil from uracil originated by deamination of cytosine. So using thymine instead makes it way easier and more stable, as any uracil inside DNA must come from a cytosine and so it can be replaced by a new cytosine.

Cytosine

This didn’t evolve for that purpose, of course. Evolution cannot predict what happens. Probably during the earliest times of life, eventually an error changed uracil for thymine and it was found to be more stable to carry information, since such a molecule wouldn’t be destroyed so easily and thus would succeed in passing its “layout” to the next generation.

It makes me wonder… Could some alien life form have found an alternative way to deal with RNA’s (or something equivalent) instability?

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Main Reference:

Jonsson, J. (1996). The Evolutionary Transition from Uracil to Thymine Balances the Genetic Code Journal of Chemometrics, 10, 163-170 DOI: 10.1002/(SICI)1099-128X(199603)10:2

https://earthlingnature.wordpress.com/2012/09/29/why-thymine-instead-of-uracil/