October 2, 2011

"Shocking" genomic mechanisms wanted

In the course of reviewing literature on transposons, I stumbled upon a classic article [1] by Barbara McClintock that was based on a Nobel Prize lecture. Finding this article (McClintock did some of the first studies of transposable elements in Zea mays) got me to thinking about the broader context of transposons and the architecture of the genome in general.

Even though McClintock's article is almost 30 years old, it features some fundamental ideas that the systems biology community would do well to reflect upon. For example, in the article she talks about genomic "shocks" of two classes: perturbations such as heat shock and DNA repair, and novel perturbations for which there is no pre-programmed genomic response to. Examples of the latter might include exposure to mutagenic agents or a large-scale injury.

While it is not mentioned in the article, this has been the basis for much work done in the area of mutational and organismal robustness. Yet current models of robustness [2] are still contingent upon specific mechanisms that confer the ability to adapt or recover from one of these shocks. What McClintock's article suggests (at least to me) that there is another side to the robustness coin. The alternate question to be asked is why generalized genomic mechanisms evolved in the first place, why/how they are maintained in evolution, and how they differ from more inducible, contextual responses.

This idea of being prepared for shocks could provide explanatory power to the understanding of regenerative capacity across animal species. Regeneration is widespread in marine invertebrate species, including totipotency in response to bodily injury. Experiments and more informal observations among vertebrates have suggested that fishes and amphibians have a more extensive set of regeneration mechanisms than do mammals. But what accounts for these differences? A formal mechanism has yet to be proposed. But the idea of a pre-programmed response for regeneration evolving in the fish/amphibian ancestor or perhaps the common ancestor of invertebrates/vertebrates is alluring.

This would not explain the loss of this response in mammalian genomes, but my guess would be that a Mammalian common ancestor traded-off this mechanism for something else. And while the idea of regenerative capacity-as-an-evolutionary tradeoff [3] is quite speculative and perhaps controversial, it is still worth considering regeneration in the context of a given genome's shock-absorbing capacity.

[1] McClintock, B. (1984). The Significance of Responses of the Genome to Challenge. Science, 226(4676), 792-801.

[2] Kitano, H. (2004). Biological Robustness. Nature Reviews Genetics, 5, 826-837.

[3] Weinstein, B.S. (2009). Evolutionary trade-offs: emergent constraints and their adaptive consequences. PhD Dissertation, University of Michigan.

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