Friday, 21 December 2007

biochemistry - Why is uracil used in RNA rather than thymine?

Thymine has a greater resistance to photochemical mutation, making the genetic message more stable. This offers a rough explanation of why thymine is more protected then uracil.



However, the real question is: Why does thymine replace uracil in DNA? The important thing to notice is that while uracil exists as both uridine (U) and deoxy-uridine (dU), thymine only exists as deoxy-thymidine (dT). So the question becomes: Why do cells go to the trouble of methylating uracil to thymine before it can be used in DNA? and the easy answer is: methylation protects the DNA.



Besides using dT instead of dU, most organisms also use various enzymes to modify DNA after it has been synthesized. Two such enzymes, dam and dcm methylate adenines and cytosines, respectively, along the entire DNA strand. This methylation makes the DNA unrecognizable to many nucleases (enzymes which break down DNA and RNA), so that it cannot be easily attacked by invaders, like viruses or certain bacteria. Obviously, methylating the nucleotides before they are incorporated ensures that the entire strand of DNA is protected.



Thymine also protects the DNA in another way. If you look at the components of nucleic acids, phosphates, sugars, and bases, you see that they are all very hydrophilic (water soluble). Obviously, adding a hydrophobic (water insoluble) methyl group to part of the DNA is going to change the characteristics of the molecule. The major effect is that the methyl group will be repelled by the rest of the DNA, moving it to a fixed position in the major groove of the helix. This solves an important problem with uracil - though it prefers adenine, uracil can base-pair with almost any other base, including itself, depending on how it situates itself in the helix. By tacking it down to a single conformation, the methyl group restricts uracil (thymine) to pairing only with adenine. This greatly improves the efficiency of DNA replication, by reducing the rate of mismatches, and thus mutations.

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