Directed repair of DNA

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news article
scientific summary
full article

This is possibly the most significant genetic discovery since Mendel & Darwin. I have not yet read the full article, but I have posted a link to the summary.

The summary states that an emergency store of genetic information may exist and be capable of restoring damaged genes to a functional state. The genetic information is proposed to be RNA transcripts of DNA from previous generations. RNA signalling molecules have been shown to travel between cells and act as intercellular communication signals, but only limited information was previously available regarding transmission of RNA between generations. The other novel component of the proposal is the suggestion that RNA is used as a template to repair DNA. A wealth of examples suggest that this should be possible, but I can not think of an immediately obvious example where this has been demonstrated. Together, these new activities of RNA provide a previously unknown mechanism whereby genetic integrity can be maintained.



The summary that I read did not indicate whether the source of the RNA was germ line or somatic cells, but it is not unreasonable to suppose that the source of the RNA was somatic cells (in which the bulk of transcriptin takes place). This leaves open the possibility that not only repair of modified sequences can occur, but also the directed mutation of specific sequences which might be modified to advantage. How might this happen?

If an organism is poorly adapted to deal with a situation or environment, it may maximally express genes that encode products which are essential to survival. RNA signals from such genes may be directed to the germ line where they can identify the target sequence and alter (by a mechanism that is not yet known, but which may resemble that described in the linked article) the sequence. This model does not yet propose how the changes would occur or whether they could be directed to be advantageous.

Edit:
I looked and the authors actually make a similar suggestion in the original publication:

"Perhaps even more intriguing is the possibility that the inheritance
of non-genomic templates occurs in wild-type and hth plants, but
the rate at which those templates are used to modify genomic
sequences is elevated in hth as a result of an indirect ‘stress’ put on
the plant by the absence of the HTH gene product. Under these
circumstances one could envisage a mechanism in which additional
allelic information is maintained outside the normal genomic
context but could be used under conditions that compromised
the continued functioning of the organism."


Plant scientists have long proposed that gene overexpression could trigger epigenetic gene suppression. Such suppression has since been shown to involve RNA signals. Somatic epigenetics in mice has been shown to be passed on through the germ line in rare instances. All of the pieces seem to be falling into place to suggest that directed and advantageous genetic change is possible based on signalling from the soma to the germ line.



The current report helps to address the evolutionary problem of organisms drifting into genetic disrepair. A genome containing 3 billion nucleotides will not be appreciably disadvantaged by any single genetic change unless it is severely deleterious. The same argument can be put forward regarding the maintenance of rRNA gene clusters. In that case, gene conversion is deemed to be the solution. The present report can be viewed as intergenerational gene conversion.

Another evolutionary problem is that of evolutionary agility, specifically the lack of such agility in organisms with long generations, small progenies and limited population sizes. Directed, advantageous genetic change could explain rapid evolutionary radiations and, actually, the source of genetic variability proposed by Darwin to be the cornerstone of his hypothesis. Neither he nor others have adequately explained the source of such variability. In lectures we mention a "low frequency of advantageous genetic changes" but don't really delve into the likelihood of such change.

Can we take this one step further? How easy is it to make a de novo change that is really advantageous and does not have secondarily disadvantagous effects? How easy has it been for geneticists to engineer a plant to be resistant to pathogens without causing susceptibility to other pathogens or disadvantagous developmental side effects? Positive genetic change is hard work. The difficulty of achieving positive genetic change would be reduced if the germ line of an organsim could sense all genes whose insufficient function was leading to problems of physiological or reproductive fitness. If this level of sensing could occur, real possibilities for positive change could result. An organism that achieved such a capacity would be the beneficiary of an evolutionary windfall not experienced since the ascendency of complex multicellular eukaryotes during the Cambrian radiation.