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MCAT TOPIC REVIEWS & RESOURCES

Biological and Biochemical Foundations of Living Systems

Genetic Code

Central Dogma: DNA → RNA → protein

The Central Dogma is a model of genetic information flow that outlines the production of proteins from the encoded instructions in DNA through RNA and finally into the amino acid sequence of the protein itself.

The two processes connecting this flow are transcription (DNA → RNA) and translation (RNA → protein).

The triplet code

Following a DNA template, transcription has an end product of a RNA strand that is in turn employed as the template for the next step, translation, which has the protein polypeptide (amino acid sequence) as its product.

More specifically, the nucleotide sequence of the DNA template dictates the nucleotide sequence of the RNA that then goes on to dictate the sequence of amino acids for the polypeptide. This reading of the RNA nucleotides is performed in triplet with three nucleotides at a time determining the next amino acid in sequence for the polypeptide. (You will find there are a number of functions different RNAs may perform; this type of RNA that is used as a template in translation is termed mRNA, messenger RNA, as it delivers the instructions encoded in DNA to produce a specific amino acid sequence).

A group of three RNA nucleotides read together to encode for a specific amino acid is termed a codon. Each codon then will have three places, each filled in by one of the four nucleotides present in RNA: adenine (A), cytosine (C), guanine (G), and uracil (U). With three spaces and four possible nucleotides to fill each space, there are 4 X 4 X 4 = 64 possible codon combinations. Each combination then acts as an instruction (a triplet code) for starting, continuing with a specific amino acid, or ending the sequence.

Codon-anticodon relationship

Codons are three-nucleotide sequences read along a strand of RNA (specifically mRNA). The translation machinery responsible for performing this reading of the codon use their own specific three-nucleotide sequence called an anticodon to match up with each codon. This machinery is a second type of RNA called tRNA, transfer RNA, for its roll in connecting (transferring) the appropriate amino acid to the polypeptide sequence.

Codons and anticodons match by base pairing, such that codon AUG with match with anticodon UAC according to complementary base pairing of A with U and G with C.

Degenerate code, wobble pairing

With 64 possible codon combinations and only 20 amino acids to be selected from, there is some redundancy in the code with multiple codons encoding for the same amino acid. This redundancy is referred to as degenerate code in that it lacks distinction of one codon per amino acid with instead multiple possible codon combinations for a specific amino acid (or ending the strand).

Looking at The Genetic Code, namely what each codon encodes for, you will see that the third position in the codon is often flexible for a specific amino acid. For example, CGU, CGC, CGA, and CGG all encode for arginine. This flexibility in the third position is termed the wobble effect or wobble pairing due to loose bonding between codon and anticodon at the third position.

Missense, nonsense codons

Missense codons result from a mutation that changes a position in the codon. Depending on the position changed and the specific nucleotide substitution, a missense codon may or may not encode for a different amino acid. A change in the nucleotide in a third wobble position, for example, may not effect the outcome of the amino acid.

Nonsense codons are a type of codon responsible for ending the polypeptide sequence. A nonsense codon does not have a matching tRNA. Instead, release factors take the place of a matching tRNA, leading to the termination of the sequence. A mutation creating a nonsense codon will prematurely end the polypeptide.

Initiation, termination codons

AUG, which encodes for methionine, is the start codon that initiates translations. Therefore Met is always the first amino acid of the polypeptide sequence (as well as possibly appearing later in the strand). UAA, UAG, and UGA are the stop (nonsense) codons responsible for termination of translation.

Messenger RNA (mRNA)

As mentioned, the process of transcription produces mRNA from reading a DNA template. This initial product, or pre-mRNA, will be processed into mature mRNA which is in turn used as the template for translation. The processing includes the addition of a 5' cap, a poly A tail at the 3' end, and splicing (removal of introns; or removal of certain exons in the case of alternate splicing).

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