Genetic Encoding questions

[binarypearl]

Hi, I'm a computer scientist who has recently become very interested in genetics.

 

I have been studying how amino acids are encoded and decoded. I have two questions that came up and wanted to see if anyone could help shed some light on these:

 

1. Methionine is known as the Initiator or Start codon, which is coded AUG. This makes sense to me, but I noticed that Methionine can also exist in a gene where it is not the Start codon. For example, in the gene Beta-defensin 4A (2), The 16th codon is Methionine again (http://www.uniprot.org/uniprot/O15263). So my question is, how does the Ribosome (I believe that's the correct structure) able to distinguish between Methionine as the Start codon and Methionine at some other location on a gene?

 

2. Most amino acids have multiple codon codes (for example: Phenylalanine can be UUU or UUC). From a computer science standpoint, that indicates to me that those two codons are unique. So even though they both code for Phenylalanine, is there a possibility that UUU and UUC in fact mean two different things?

 

--Shaun

[CharonY]

1. Only the first methionine is recognized as starting codon (in bacteria, formyl-metionine is actually incorporated at the onset of translation). Further AUG are treated (for the most part) as regular methionine. A simplified way to visualize this is that the ribosome is formed at the ribosome binding area of the mRNA, the mRNA is then pulled through until the start codon is recognized. From there the elongation of the protein is processed normally, until it is terminated. In some cases (mostly viral genomes) genes can be stacked. In this cases a second ribosome binding site can be found within a larger coding area so that the initiations starts further downstream.

 

2. The implications can be quite deep. To understand some of them, one has to know that the genetic code is realized by the presence of tRNA that carry a specific aa with a respective anticodon, which recognizes the particular sequence on the mRNA. So mechanistically each codon requires the presence of their respective tRNA. I.e. a tRNA carrying the respective anticodon, coupled with a given amino acid (phenylalanine in this case).

Some implications:

- protein synthesis can be controlled by tRNA levels. One particular tRNA may be present in low concentrations, for whatever reasons, and genes carrying their codons may not become (fully) translated.

- mutations within each codon can result in different amino acids (not so much an issue in this example), likewise, mutations in the genes coding for the respective tRNAs will result in different effects (as these are different genes)

- on a similar note, different bases (uracil vs cytosine in this example) have different propensity to mutate in presence of different agents, so mutation rates may differ

[binarypearl]

Thanks CharonY! There is a lot of good information here.

 

I didn't realize there was a binding area on the mRNA, in which the start codon AUG is just one part of that. So that makes sense to me now how you can have Methionine as a start codon and at other locations, because there is more to the start of a gene than just the start codon. I found something called 'Kozak consensus sequence', which looks to go more in depth about the start sequence of a gene.

They way I view mRNA and tRNA, is that mRNA is a long strand of codons that indicate which amino acid is to be next in the protein chain. From what I have read and the videos that I have seen, tRNA instead seems to a be a pool of separate structures, one per amino acid. As you described above, each tRNA structure has 1 amino acid attached to it, and the anticodon of that amino acid. While probably technically somewhat inaccurate, the way I think of it is when the mRNA codon is in the ribosome for reading, it sort of turns on a type of magnet (covalent bonds?) that attracts the specific tRNA structure with the amino acid that the mRNA is coded for. If I understand this correctly then, if a person is lacking a certain amount of an amino acid, this could possibly result in some type of gene mutation.

 

I'll also have too look more into stacked genes that you mentioned above. Viruses are another fascinating subject.

 

--Shaun