The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

Frequently-Asked Questions
The effect of this in mitochondria was slight enough to be survivable. A few
mitochondrially-encoded proteins would have ended up having a few extra amino acids
tacked on their ends, and that happened not to do any real harm.* So the change stuck. But
the effect on gene transfer to the nucleus was immense. Now that UGA coded for tryptophan,
it was possible for base pairs in the mitochondrial protein-coding genes to mutate silently to
create UGA codons where there had previously been UGG. Such mutations would be silent
in the mtDNA, because UGG codes for tryptophan already, so the encoded protein would
have an unaltered amino acid sequence and the mitochondrion would be unaffected. In a
very short time (by evolutionary standards), roughly half of the tryptophans encoded in the
mtDNA would have come to be specified by UGA rather than UGG. Now consider the
protein product of a mitochondrially-coded gene which is transferred to the nucleus after
this short period. Rather than the minimal effect of having a few extra amino acids tacked
onto its end, it will have the opposite experience: it will be brutally truncated at the first
UGA, since the cytoplasmic translation machinery still interprets UGA as “stop.” A successful
transfer would thus require reversal of all the UGG-to-UGA changes that had accumulated
in the transferred gene, without any other deleterious mutations being introduced in
the meantime: a phenomenally unlikely scenario.
It is therefore no surprise that animals have failed to transfer any more genes except
ATPase 9 and maybe ATPase 8. It is also no surprise that those two are the ones that have
been moved. They are extremely small genes: ATPase 8 is only 50 to 70 amino acids long,
and ATPase 9 less than twice that, compared to 300 or more for the average protein. The
number of amino acids in a protein determines, on average, the number of base pair
substitutions that would have to occur in a transferred gene in order to restore its consequent
amino acid sequence to what the mitochondrial translation machinery would produce; since
they must all be done if the gene transfer is to succeed, the difficulty of that transfer is thus
an exponential function of the length of the protein. The shortest genes have had the easiest
time.
It should be noted that the UGA switch was not the end of the story. The mitochondrial
genetic code has remained under only this relatively slight pressure to remain the same
since that time, and many other drifts have taken place, so that different animal phyla have
different codes, and for example our mitochondrial code differs in four codons from the
universal one 7 (see Table 10.1). This fact has been cited as a challenge to the argument outlined
above: the logic is that if the code drift mostly happened recently, but the gene transfer froze
much longer ago, then code drift can’t have been the reason gene transfer froze. 12 But this is
wrong, since it is not the average timing of the code drift which matters, but the timing of
the first drift. This is particularly true because that first drift was a change from STOP to
coding, causing truncation of any transferred proteins as explained above; a change from
coding to STOP or from coding to coding would have the much weaker effect of changing
or appending some amino acids to the transferred protein, which might often not destroy
its function 13 (see Table 10.2).
Similarly, one might argue that it still seems to be extremely hard to get genes across,
even in plants, given that only two recent cases (the Vigna cytochrome c oxidase subunit 2
and the Selaginella cytochrome c oxidase subunit 3) are known. Yes, it probably is hard,
given the apparent difficulty in overcoming these proteins’ hydrophobicity. But also, this
* Plants probably retain the standard code largely because they still have upwards of 20 mitochondriallyencoded
genes, including many ribosomal proteins. A few extra amino acids may usually be harmless, but
not always: it can quite easily do harm to a protein's functionality. The more proteins are extended, the less
is the chance that all the extensions will be harmless.
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