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Genetic Backup Files

arabidopsis.jpgThe current issue of Nature includes a report by biologists at Purdue University about the Arabidopsis thaliana plant's ability to reverse mutations in subsequent generations. While the article itself is only available to subscribers, summaries are available at Nature News, the New York Times and the Washington Post, among others. This is one of those discoveries that sounds a little esoteric at first, but could have some pretty important implications.

In the traditional understanding of genetics, organisms which reproduce sexually only express mutations when both parents carry the trait, while organisms which reproduce asexually will pass any mutation along to subsequent generations. Arabidopsis thaliana, a mustard weed, is of the latter type, reproducing through self-fertilization. The plants being studied had developed a mutation known as "hothead," where the flowers were fused (as in the photo). The researchers noticed that about 10% of the offspring of the mutated plants had reverted to the normal configuration and, when examined, the normal non-mutated genes, the same as the grandparent plants. In effect, the mutation had been wiped away.

They spent over a year testing various explanations for the phenomenon, from external pollen contamination to normal DNA repair mechanisms; none of the conventional theories worked. The only remaining answer was that "backup" or "cache" copies of the genes existed, but an examination of the DNA found nothing of the sort. The Purdue team has come to believe that the most likely location for the backup is the RNA, which is inherited separately from the DNA. As RNA is traditionally considered to be used primarily to help DNA replicate, and is known to be prone to many more errors during self-copying, RNA has not been studied as closely as DNA.

The upshot: under certain stress conditions, Arabidopsa thaliana is able to restore its correct genome from a backup file during reproduction. While the Purdue team has identified this phenomenon as happening in a single particular species, there is evidence that it happens more generally across plant species; the Post article notes that reversion from mutation is not uncommon in lab plants, but is often assumed to be the result of external contamination or researcher error.

But perhaps most interestingly, the phenomenon may not be limited to plants. It could show up in animals, even in people.

A similar process might even go on in humans. This is suggested by rare cases of children who inherit disease-causing mutations but show only mild symptoms, perhaps because some of their cells have reverted to a normal and healthier genetic code.

If humans do correct their genes in this way, Pruitt suggests that the procedure might be usefully hijacked by researchers or doctors. They might be able to identify the RNA molecules that carry out the repair and use them to correct harmful mutations in patients.

The implications of this discovery are manifold. It's a sobering reminder that DNA is not the sole determinant of biological outcomes. It's a warning flag for all manner of biotechnology research, as it means there may be a broad mechanism able to reverse engineered genetic changes; this could mean that conclusions about interactions between GMOs and non-engineered organisms will need to be re-examined in light of possible reversions of parts of the new code. If a similar mechanism is discovered in animals, gene therapies and human germline biotechnologies will face more significant challenges than currently anticipated.

And, as the researchers observe, it could have important medical utility. Triggering the mechanism to fix mutations is one scenario; using the "backup" genetic data as templates for genetic therapy or corrective bioengineering is another. Of course, it may not apply to animals, or the mechanism could work in a very different way. Nonetheless, this discovery has opened an unanticipated -- and potentially quite valuable -- pathway for research.

Comments (3)

Interesting post! This could provide a great alternative to neutered viruses for gene therapy delivery. From an evolutionary standpoint, I find it a bit confusing, however; wouldn't this work against the evolutionary model of punctuated equilibrium and advancement through successful mutuation by mitigating the negative effects of poor mutations or adaptations? Its sort of an easy-out for genetic risk-takers, which would ultimately lead towards a more homogenous gene pool, would it not?

Tim McGee:

Great Article and fascinating find. As for above comment, I'm not convinced that a latent mutation re-grade of 10% is likely to cause a gene pool to become homogenous...you still have 90% with the mutation plus every other gene with options to mutate. But one very interesting conclusion is that this re-grade in fact could be indicative of the hypothesis that this gene is simply "easy" to mutate, and represents a new way of thinking about mutation rates of genes.

janine cascio:

my last name is cascio :)


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