8) Start codon issues

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Alternative Start Codon Issues

Possible start codons AUG (most common in archaea), GUG and UUG [1].

Olivia came across a very interesting conundrum because she checked and tried to verify a lot of the computer's work:

When the start codon is not AUG, is the first amino acid in the protein's primary sequence a Met or the correct amino acid for that codon triplet?

I think it would be an interesting side study but it may require wet lab work to decipher whether or not the first amino acid is really Met when an alternative start codon is used. It may also be interesting to look for a trend in the genes that begin with an alternative start codon.

There is not much published research I could find on this issue but the articles/links below are summarized:

1). Yokobori, et al establishes that ". . . potential start codons ATR (Met), ATT (Ile), TTG (Leu), and GTG (Val) . . . " [5] do not all encode Met. I unfortunately only received references to this article through other articles, but I will continue searching for the following article (which may hold some answers).

2). Wikipedia and other basic Encylopedia's claim the following. "Interestingly when an alternative start codon is used, it gets translated as methionine - even if the codon might normally encode a different amino acid. This is because a separate [tRNA] is used for initiation."

3). Wikipedia also asserts that , "Alternative start codons (depending on the organism), include "GUG" or "UUG", which normally code for valine or leucine. However, when used as a start codon, these alternative start codons are translated as methionine or formylmethionine" [3].

4). " It is generally thought that the first amino acid incorporated into the polypeptide chain is methionine. However, in some cases where an initiator tRNA is altered, the non-AUG start codon can initiate protein synthesis with amino acids other than methionine" [4].

Good Articles to Reference:

1. Transcription and translation in Archaea: a mosaic of eukaryal and bacterial features.

2. The Genetic Codes

3. Touriol C, Bornes S, Bonnal S, et al. (2003). "Generation of protein isoform diversity by alternative initiation of translation at non-AUG codons". Biology of the cell / under the auspices of the European Cell Biology Organization 95 (3-4): 169–78. PMID 12867081. (I could not find a hard copy of this yet).

4. Non-AUG translation initiation of mRNA encoding acidic ribosomal P2A protein in Candida albicans

5. Yokobori, S., Ueda, T., Feldmaier-Fuchs, G., Paabo, S., Ueshima, R., Kondow, A., Nishikawa, K., and Watanabe, K. 1999. Complete DNA sequence of the mitochondrial genome of the ascidian Halocynthia roretzi (Chordata, Urochordata). Genetics 153: 1851–1862. [PubMed]