Previous posts have shown Hsp90 to be a molecular buffer allowing rapid morphological changes in times of stress. As will be discussed below, such a buffering function supports the evolutionary theories of punctuated equilibria, hopeful monsters and canalization.

So…, this last post will end with the final conclusions based on the arguments presented in the previous 4 posts. But, first….Two fundamental questions:

1. Even if Hsp90 can promote rapid changes in phenotype (appearance) how is this change retained (fixed) for future generations ?

This fixation has been demonstrated to occur (see Sangster TA et al.), and the traits become independent of Hsp90. The exact mechanism(s) however remains to be elucidated.

Nevertheless, temporarily compromising Hsp90 function (either by drugs or by temperature rise) is sufficient for fixing new traits. Simulations seem to show that knocking out the genes for key proteins (not necessarily heat shock proteins) lead to increased phenotypic diversity, and thus the underlying cause may be genetic fixation. However, interplay between epigenetic and genetic mechanisms has been suggested and been backed up by experiments. Thus fixation probably happens through yet to determined genetic as well as epigenetic mechanisms, or a combination of both. A model for epigenetic fixation is given in the thumbnail below:

Models for genetic fixation follows the theory of canalization with Hsp90 functioning as the Waddington’s widget (see Semin Cell Dev Biol. 2003 Oct;14(5):301-10). This is discussed further under the next bulletpoint, the second question…..

2. Does these aspects of Hsp90-function fit into current models of evolution ?

Yes, although some of these theories are controversial. First we have the idea of punctuated equilibrium and hopeful monsters discussed in my previous post. To expand on these ideas let’s also include the theory of canalization. Canalization explains punctuated equilibrium by referring to an organisms buffering capacity (to counter the potential deleterious effects of mutations). The theory was put forward by C. H. Waddington more than 50 years ago, but is still controversial it seems. Hsp90 is a molecular explanation of the canalization concept in that organisms with different genotypes express the same phenotype until times of stress. There are also indications that other heat shock proteins or other “signaling hub”-proteins or even miRNA can serve such buffering functions (see references within this review).

Taken together, these controversial evolutionary theories and the experimental evidence on Hsp90 supports one another, and a paradigm shift in evolutionary biology is in place. Darwins theories are correct up to the point of gradual and constant evolution of traits. Evolution instead, occurs in bursts. This series of blogposts have conveyed the molecular evidence for such punctuated equlibria and canalization, which comes from studies on the molecular chaperone Hsp90. I hope I have enlightened and convinced at least some evolution biologists into believing that Darwins theories can be expanded to include these (no longer controversial) theories.

There are however, a lot to work out in terms of the underlying molecular mechanisms for Hsp90 (and/or other buffering bioactive molecules ?) in canalization. To end this blogpost-series I will therefore quote the closing remarks from Salathia N and Queitsch C‘s review in 2007:

“Clearly, organisms have succeeded in integrating multiple canalization mechanisms into robust wild-type phenotypes which can respond appropriately to environmental perturbations and evolve new shapes and functions over time. Now it is up to us to determine how molecules as diverse as a molecular chaperone, chromatin remodeling proteins, and the RNAi machinery interact coherently to achieve such synergy, a truly fascinating and worthy field of future inquiry.”