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Why is the start codon on an mRNA always AUG and the stop codon always UAA, UAG, UGA?

  1. Nov 28, 2012 #1
    Is there a reason for this or is it 'just like that'?
  2. jcsd
  3. Nov 28, 2012 #2
    What exactly do you mean by 'always'? do you mean why it is like that for all organisms? Or do you mean for all genes?
  4. Nov 29, 2012 #3


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    Re: Why is the start codon on an mRNA always AUG and the stop codon always UAA, UAG,

    So far it seem to us "just like that" ("frozen accident"). Proposals for reasons have been made (eg. stereochemical), but all the proposals are problematic at the moment.

    http://parkinson.cos.ucf.edu/Courses/PCB6677/old/pdf/rewiring-KnightFreelandLandwebber.pdf [Broken]
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  5. Dec 1, 2012 #4


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    Re: Why is the start codon on an mRNA always AUG and the stop codon always UAA, UAG,

    Although most mRNAs use AUG as the start codon, this is not always the case. For example, in E. coli, almost 20% of protein coding sequences use alternative start codons (mostly GTG and TTG) (1). A recent studies of mammalian cells have demonstrated the use of alternative start codons in eukaryotes as well, including a CUG codon that gets decoded by a tRNA different from the initiator tRNA (2,3).

    As for stop codons, although we don't know of any alternative stop codons, having three stop codons does not seem to be necessary. For example, some organisms have reassigned one of the stop codons to encode for amino acids, and there is even an effort by some synthetic biology labs to completely remove one of the stop codons from E. coli (4). Thus, it certainly seems like organisms can function perfectly well with just two stop codons, and it may be the case that an organism could function with only one stop codon.

    (1) Blattner et al. 1997 The Complete Genome Sequence of Escherichia coli K-12. Science 277: 1453. doi:10.1126/science.277.5331.1453
    (2) Ingolia et al. 2011 Ribosome Profiling of Mouse Embryonic Stem Cells Reveals the Complexity and Dynamics of Mammalian Proteomes. Cell 147: 789. http://dx.doi.org/10.1016/j.cell.2011.10.002 [Broken]
    (3) Starck et al. 2012 Leucine-tRNA Initiates at CUG Start Codons for Protein Synthesis and Presentation by MHC Class I. Science 336: 1719. doi:10.1126/science.1220270(4) Isaacs et al. 2011 Precise manipulation of chromosomes in vivo enables genome-wide codon replacement. Science 333: 348. doi:10.1126/science.1205822
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  6. Dec 2, 2012 #5


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    Re: Why is the start codon on an mRNA always AUG and the stop codon always UAA, UAG,

    The question why the start and stop codons are what they are seems no different from the question of why all other codons are what they are and not something else. Why is GGG a codon for glycine and GUG for valine? Why not the other way round?

    The immediate 'cause' is that there is in waiting a glycl t-RNA containing in the appropriate place GGG's anticodon CCC and a valyl t-RNA containing GUG's anticodon CAC. The reason these things are in waiting is that an enzyme has specifically catalysed gycylation of the CCC containing t-RNA and does not do that to the t-RNA containing CAC at the anticodon site, which is instead valylated by a different enzyme. So the 'reason' at this level is the specificity of recognition of the anticodons by the aminoacylating enzymes. Into which the t-RNA secondary structure you will surely read about enters.

    So really there is not a question about codons, the question has to be about the whole recognition system in which they function, or rather which functions around them. It is like the system works via recognition of some conventions which have been evolved by Nature.

    There is no evident reason the code has to be the way it is, i.e. you can easily imagine a life using the same mechanisms as ours except GGG codes for valine and GUG for glycine and the enzyme recognition sites too are switched around. I think there is not yet a convincing and accepted theory for that, which would certainly be about early origin and evolution of life.

    Coming back to your original question about start: to first approximation the start codon is just a codon for methionine, so the same question as for any other codon. To second approximation the start site has other information besides the codon. It has specific sequences ("Shine-Dalgarno" and "Kozak") 5' to the start codon to tell the ribosome and enzymes to start there.

    For possible explanations of how things came to be as they are you have already been given some references, to which I add
    http://www.imb-jena.de/~sweta/genetic_code2/evolution.html [Broken]
    to start following up (quite a big job for you though). I have not followed this stuff much myself, but I say that as my limitation not as a virtue which stuffier academics might. But they are also influenced by the fact it is hard enough to get students to know and understand what is known without distraction by more speculative questions. And I do not think there is a hope of a sound theory of origins without good knowledge of how things are now. It would involve looking at the protein-RNA macromolecular complexes in detailed structure, not just their schematics I'd think. So the teachers' focus and the speculation are not in contradiction. Maybe you have the time and energy to follow up the whole question - if not at the moment then your first guess, it is just how things are will do for now. :smile:
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