The Mitochondrial Free Radical Theory of Aging - Supernova: Pliki

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The Mitochondrial Free Radical Theory of Aging
Table 10.1. Deviations from the standard code of various taxa’s mitochondrial
genetic codes
Taxon UGA = Trp? AUA = Met? AGR = Ser? AGR = stop? CUN = Leu?
All vertebrates yes yes no yes no
Most yes yes yes no no
invertebrates
Saccharomyces yes yes no no yes
Most other sometimes no no no no
fungi
Plants, most no no no no no
algae
Most primitive yes no no no no
eukaryotes
See ref. 7 for more detail and primary references. R stands for “A or G”; N stands for “any base.”
overlooks the fact that far fewer plants than animals have yet had their mitochondrial genomes
sequenced, 14a so it is quite possible—in fact, many would say absolutely certain—that more
such cases will be found.
Another confounding factor is that, judging from the situation with Vigna, such transfers
may be very easy to overlook. There are two stages to a transfer: the introduction of the
DNA into the nuclear genome and its loss from the mitochondrial one. The functional
transfer occurs when the nuclear copy is “turned on” and the mitochondrial one turned off;
this must occur very soon after the DNA arrives in the nucleus, since otherwise it would
undergo random mutations that would render it useless. But the inactive mitochondrial
copy can, in theory, stay put indefinitely, since it is inactive. One might guess that it would
usually be deleted rather quickly; but if we recall that there is a lot of “junk DNA” in plant
mitochondria (as against essentially none in animals), perhaps this is not so obvious. And
in fact, Nugent and Palmer found when they examined other legumes that the entire bean
taxon uses a nuclear-coded cytochrome c oxidase subunit 2, even though only Vigna has
lost the mitochondrial copy! This means that the inactive mitochondrial copy has been
retained for up to 100 million years in most beans. The implication for discovery of other
transfers is clear: simply probing the mtDNA by in situ hybridisation with genes from other
organisms will not necessarily detect a transfer. The only reliable assay is more laborious:
Northern blotting of fractionated samples, to detect whether the messenger RNA is localized
in the mitochondria or the cytoplasm.
In closing this topic, it should also be mentioned that a number of other proposals
have been put forward to explain why we retain our mtDNA. These reasons are potentially
relevant to the possibility of retarding aging by mitochondrial gene therapy, which is the
subject of Chapter 15. Discussion of these will therefore be deferred to Section 15.8.