Why thymine instead of uracil?

by Piter Kehoma Boll

ResearchBlogging.org 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:


The only difference between it and thymine is the presence of a methyl group 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.


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?

– – –

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



Filed under Evolution, Molecular Biology

25 responses to “Why thymine instead of uracil?

  1. Great discussion. Also an interesting topic that I’ve never actually gone so far as to look up to see what’s been proposed. I’d definitely like to reblog this on my site where my students can read it if you don’t mind.

  2. Reblogged this on DownHouseSoftware and commented:
    An interesting look into why DNA and RNA might use different nucleic acids for what seems to be essentially the same purpose (namely Thymine and Uracil).

  3. Thank you so much for this information 🙂 it helped me a lot with for genetics homework!

  4. MUCH satisfying explanation thanx it helped me!!

  5. Patricie

    Hi! Very nice post, it helped me a lot.
    Just a question – when I googled it, it says everywhere that RNA is actually more stable that DNA while suffering UV radiation. But here you say that dNTPs are less susceptible to damages by UV than NTPs .. So how is it?

    • Piter Keo

      Thank you for your comment.
      Abour your question, I think the point is that deoxyribose is more stable than ribose because a C-H bond is more stable than a C-OH bond. So a single nucleotide of DNA is more stable than its RNA counterpart, but the whole chain forming a molecule of DNA is less stable than RNA when dealing with UV radiation.

      • Alfred

        Hello Piter
        I just discovered this article and comment during my info-search for a big assignment in high-school about inactivation of bacteria and vira with UV light.
        Do you know if this (with RNA being more stable than DNA) has anything to do with Uracil being less likely to make a dimer with itself, than Thymine?
        Greeting from Denmark

      • Piter Keo

        Hi, Alfred. Actually RNA is less stable than DNA because of the presence of a hydroxyl group on the pentose, which makes RNA more likely to suffer hydrolysis. But I don’t know whether the likelihood of Uracil and Thymine to form dimers has any relevance on the stability of the molecules.

  6. AJAY Kumar

    Very nice discussion…it help me a lot.my question is which enzyme is required for dehydroxylation at c3 of ribose

  7. Rupa

    Thank you so much for sharing this. Very helpful indeed. I would like to share this with my students.

  8. Ankita galgale

    Thank u so much for sharing this information with us.. It really helped me with my molecular biology work.

  9. Qurat

    Excellent answer

  10. Hi! the explanation you gave is really nice. inspired by this, I read couple of papers dealing with origin of DNA from RNA. Could it be possible that time of DNA formation coincided with time of origin of plant photosynthesis?
    Thanks a lot

    • Piter Keo

      Thanks for your comment!
      I don’t think so. Certainly DNA originated before the rising of the most recent common ancestor of all lifeforms and photosynthesis, as performed by plastids, seems to have evolved only once, in the lineage leading to modern Cyanobacteria and plastids.

  11. Joseph Caponi

    I’m glad my genetics professor goaded us into reading this, it was pretty interesting

  12. Dr. Naveeda Zaigham

    Excellent discussion. Very helpful indeed but I would only like to ask one question that if one nucleotide of DNA is more stable then how could the whole chain of DNA be weak when they are present collectively?

  13. well dear great and tasty discussion herein, i have some points to link with this first regarding using deoxy-ribose sugar instead of ribose is that in ribose the additional ‘O” provides more reactivity. and C-H bond is more stable, reason behind using thymine inplace of uracil may be that thaymine has additional methyl group and provides steric hinderince

  14. Pingback: Por que timina no lugar da uracila? | Natureza Terráquea

  15. Oscar Sapkota

    Great discussion! Thank you very much for all the wonderful information! However, I still have a wrinkle in this regard; I had stumbled across a statement while studying for an exam, and I still haven’t got a satisfactory explanation for it. The statement is: uracil enables mRNA to pass through the envelope and take the code of the DNA into the cytoplasm, whereas the presence of thymine in DNA restricts its passageway out of the nuclear envelope. Now the question is: how does Uracil help in that? And how does the presence of thymine restrict its passage out of the nuclear envelope?

  16. Oscar Sapkota

    Great discussion and wonderful explanations! However, I have a minor wrinkle about the topic under discussion. As I was going through the SAT II Biology section, I stumbled upon this statement:
    RNA-RNA is a 5-carbon sugar that possesses an extra oxygen atom [compared with DNA] and replaces thymine with the base uracil, thus enabling it to pass through the nuclear envelope and take the code of DNA to the cytoplasm.
    , and no further explanation was given about a segment of the statement: How does having uracil instead of thymine gift RNA with the ability to leave the nuclear envelope? Can you help me out to answer this question?

    • Piter Keo

      Thank you for your comment!

      Regarding your question, I don’t think that those differences have anything to do with passing the nuclear envelope, since both DNA and RNA are present in prokaryotic cells, which lack a nucleus.
      The difference in the sugar is likely an adaptation to turn DNA into a more stable molecule. An -OH tail is very reactive and is useful in RNA to allow the molecule to be easily decomposed after having fulfilled its task. In DNA, replacing an -OH in the sugar for the less reactive -H ensures its stability as a permanent molecule.

  17. Joe

    Excellent post. You are rightfully Google’s first result when you search for “thymine uracil methyl.”

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