31 January, 2010

Why does thymine replace uracil in DNA?


First, some clarification.As you already know, the difference between RNA (ribonucleic acids)and DNA (deoxyribonucleic acids) is the existence of a hydroxyl (-OH) groupon the 2' carbon of the ribose sugar in the backbone.
The removal of 2' hydroxyl groups from DNA does not occur afterthe DNA has been synthesized, but rather the 2' hydroxyl groups are removed from the nucleotidesbefore they are incorporated into the DNA.
During nucleotide synthesis, a portion of the nucleotide monophosphates (NMP's) are dehydroxylated to2'-deoxy-nucleotide monophosphates (dNMP's).
This means that GMP, AMP, CMP, and UMP are converted into dGMP, dAMP, dCMP, and dUMP, respectively.
However, before being incorporated into the chromosomes, another modification,using folic acid as a catalyst, methylates the uracil in dUMP to form a thymine making it dTMP.
After further phosphorylation, dGTP, dATP, dCTP, and dTTP can be used as the building blocks to construct 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?
The answer is: methylation protects the DNA.Beside 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 ofthe 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 ofthe 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.
To sum up: the replacement of thymine for uracil in DNA protects the DNA from attack and maintains the fidelity of DNA replication.(For another take on DNA, check out this article:Inhibition of Ribozymes by Deoxyribonucleotides and the Origin of DNA.)
[Moderator Note: In addtion, the cytosine base can spontaneously deaminate to form a uracil base, which would result inundetectable C -> U mutations if U were used routinely in DNA.
Since Thymine is basically methyl-U, the cell's DNA repair mechanisms can distinguish illegitimate U from legitimate methyl-U inDNA, and make the proper repair (replacing any U with a C).
C -> U mutations in RNA do not matter as much, because RNA is synthesized inlarge quantities and is rapidly degraded in comparison to DNA. -- Steve Mack, MadSci Moderator.]


Why does RNA have uracil and DNA thymine?

Thymine in cells is made from Uracil in an energetically expensive
process, so we can assume uracil came first. Similarly sugars in
DNA (Deoxyribose) are made biosynthetically from those in RNA (ribose).
Cytosine degradation to form uracil is one of the most common
DNA mutations, but can be easily recognised and repaired.
If Uracil were present in DNA, the cell would not know which Uracil
bases to repair. Thus the use of thymine confers extra stability on
DNA. Stability that was not required in the more transient less
complex RNA world.



How did the RNA world develop into the DNA world?

The million dollar question! Nobody really knows, many people have
suggested models all of which are difficult to prove.
->The first suggested stage is that RNA transferred most of its
catalytic functions to proteins, via an intermediate stage of
enzymes containing both RNA and proteins, of which a few remain
(i.e. ribosomes and telemorase). This is sometimes called the
ribonucleoprotein (RNP) world. DNA came later as its synthesis
requires several protein-only enzymes in all branches of life.
DNA provides much more chemical stability and double-strandedness
makes repair easier. RNA genomes would have had to have been
converted into DNA genomes. DNA can still be made from RNA
today by the enzyme reverse transcriptase found in many viruses.


hi... hiren...