Friday, 28 September 2012

Preventing Mutations...Au Naturel

Cells in our body are constantly busy with replicating DNA, transcribing mRNA, and producing proteins. With all of this happening again and again and again, the probability of errors, or better known as mutations, are quite high. To prevent these unwanted variations from happening, nature has developed its own defense mechanisms.

During the replication process, the parent DNA is copied into two daughter DNA molecules. Nature had to find an effective way to create exact duplicates of the DNA without risking exposure to mutations. This is why DNA is copied through the process of semi-conservative replication. Semi-conservative replication means inside every newly copied DNA molecule, exists one original strand from the parent DNA and one newly synthesized DNA strand. By having the original parent DNA as a template, the copied DNA molecules should technically be exactly the same by simply matching pyramidines and purines. As well, with every cell division, the ends of the chromosomes, called Telomeres, slowly deteriorate. This is because every time DNA is replicated, some genetic information is lost. Fortunately, the telomere contains no important genetic information, therefore there are no errors on the important parts of the DNA.

How exactly is the DNA copied? DNA is in the shape of a double helix. In order for replication to take place the DNA molecule must be unwound with the help of the Helicase enzyme. Then a second enzyme called the Single-Strand Binding Proteins help to keep the DNA strands unwound. Now most people would think that the Helicase enzyme would start to unzip the strands starting at one end, but that would jeopardize the DNA. With the one end exposed, the DNA would become susceptible to foreign invaders and could easily break and/or mutate. This is why nature decided to have DNA replicate in "bubbles". All along the parent DNA, there would be small sections of replication. The parent DNA wouldn't unwind all at once, therefore protecting the genetic information. Instead, it would unwind little by little; here and there. By doing this, there will be a lot of tension in the DNA molecule which is why Gyrase, another enzyme, helps to rid the DNA of its stiffness. As the DNA is copied, DNA Polymerase III, the enzyme that is in charge of elongating the daughter DNA, moves along the parent strand, expanding the bubble, until two bubbles meet, thus forming a bigger bubble. The process continues until there are no more bubbles; just two daughter DNA molecules.

DNA is not only replicated, but can also be transcribed into mRNA for protein production. Once RNA Polymerase II has finished transcribing the DNA, Pre-mRNA is made. Pre-mRNA cannot be translated into amino acids yet because it contains introns. Introns are useless pieces of genetic information that do not contribute to the creation of amino acids, at least not in this particular gene. Exons are the ones that contain the codes to make amino acids. However, introns do serve some purpose; they reduce the likelihood of mutations. If there is a strand of RNA that contains only exons and a foreign invader were to attack that RNA, a mutation on the important genetic information is inevitable. But if a foreign invader were to target a strand of RNA that contains introns and exons, then the introns reduce the probability of mutations only occurring on the exons. The introns are essentially taking the "blows" for the exons.
Eventually introns are removed from the Pre-mRNA with an enzyme called the Splicesosome or the snRNPs. Splicesosomes will cut away the introns and reconnect the exons. The way they do this is very unique. Rather than just slicing and gluing haphazardly, snRNPs loop the intron. By doing this, the two ends of the exons are brought very close together. The snRNPs quickly cut off the intron, which floats away, and combines the exons. The fact that the exons were already so close leaves little time and space for invaders to mess with the coding.

Introns aren't the only way nature protects the RNA. If an RNA strand were simply floating around, the two ends of the RNA would be at risk of being attacked by water. This is why nature added a G-Cap or 5'-Cap to the 5' side of the RNA and a Poly-A tail on the other. The G-Cap contains multiple Guanine molecules and does not actually code for anything. It also signals to the ribosome where to start. The Poly-A tail contains multiple Adenine nucleotides and does not code for anything either. But by having the two caps, the RNA is safe from water. It's like the RNA has two body guards.

After the Pre-mRNA has lost its introns, it is now ready to be dispatched from the nucleus. Once translation has started the ribosome converts the nucleotides, three at a time (codons), into amino acids. Most of the amino acids can be made from multiple different codons.
In the chart we can see that Glycine can be produced by a GGG, GGU, GGA, and GGC codon. Therefore, if a mutation were to occur on the third letter of the codon, the same amino acid would still be produced. If the mRNA codon was supposed to be AGU, but was, instead, mutated to become AGC, there are no worries because serotonin would still be produced nonetheless. This is known as the Wobble Effect.

Nature works in wondrous ways to preserve our identities. Had there been none of these defense tactics, our bodies would be severely mutated and we would not be able to survive. These are only some of the ways that nature protects our genetic information. We should not take nature's work for granted. Without it, there would be no life on Earth.