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Posts Tagged ‘Hsp90’

Once again Hsp90 changes how we think about evolution

In Uncategorized on July 14, 2008 at 1:37 pm

post to news.thinkgene.com

Hsp90 and it’s possible role in evolution (as a capacitor for rapid change), I have covered extensively in the  5 post series for JustScience week 08 (Revolution Evolution, Presenting….Hsp90, How can chaperones act in evolution, Evidence for Hsp90 involvement in rapid evolution of new traits and Hsp90 to end controversies in evolution theory). Recently I found this thorough review on the subject from which I would like to share the essentials (review written by Roberta L Millstein at University of California, Davis):

Recent work on the heat-shock protein Hsp90 by Rutherford and Lindquist …. has been included among the pieces of evidence taken to show the essential role of developmental processes in evolution;

To recap, the theory is that heat shock proteins can hide genetic variation until a stressful environment exposes them to allow rapid change (evolution) of morphology and subsequently, traits.

Hsp90 acts as a buffer against phenotypic variation, allowing genotypic variation to build. When the buffering capacity of Hsp90 is altered (e.g., in nature, by mutation or environmental stress), the genetic variation is “revealed,” manifesting itself as phenotypic variation.

The theory is backed up by genetic experiments on Drosophila and Arabidopsis. Results from this research on Hsp90 lends support to channeling and “hopeful monster” theory and as such, follows the more controversial line of evolution-thinking. The review sums up many of the controversial sides of conclusions from the Hsp90 research:

This phenomenon raises questions about the genetic variation before and after what I will call a “revelation event”: Is it neutral, nearly neutral, or non-neutral (i.e., strongly deleterious or strongly advantageous)? Moreover, what kinds of evolutionary processes do we take to be at work?

My goal with the previous posts on Hsp90 was to show that the data lends sufficient support to alter and revise how we think about evolution. It seems this is the goal of the review as well.

The primary goal of this paper is to illuminate the alternative scenarios and the processes operating in each. At the end, I raise the possibility of a synthesis between evo-devo and nearly neutral evolution.

Evolution I strongly believe, is not entirely and exclusively driven by a random (and slow) constant mutation rate, but rather controlled by a number of additional mechanisms to ensure that an organism can evolve rapidly. To me, this is not controversial at all, – it does not overturn any Darwinian principles, but serves as an extention to explain the speed of evolution that has sometimes baffled us. Nevertheless, conclusions drawn from Hsp90 research remains controversial to many evolutionists, and Millstein sums it up with:

I find it somewhat ironic that people who are otherwise unorthodox in their thinking with respect to evolution are so orthodox when it comes to adaptationism. After all, as the late Gould argued, nonadaptive approaches were left out of the evolutionary synthesis (Gould 1983) just as developmental processes were (Gould 2002).

Which to me, a molecular biologist gone amateur evolutionist, is a good ending note. Reviews like this, one can only hope, will lend credibility to alternative thoughts on mechanisms of Darwinian evolution. Which is surely needed to fully understand the beauty and complexity of the molecular mechanisms that shapes our world.

Note: the review I have linked to is open access, but apparantly only a draft, the final version is available here, but isn’t open access (shame on you Biological Theory and MIT press Journals).

How everything is a mess and still ok

In Uncategorized on May 26, 2008 at 9:09 am

post to news.thinkgene.com

I have recently finished reading a Nature news feature on noise in gene expression (The Cellular Hullabaloo). It left me with this increased understanding of cellular processes and in terms of controlling chaos, fitted nicely with something I have blogged about before, which is Hsp’s (especially Hsp90).

According to this news feature, several studies have found that there are significant differences in the expression of genes both in duration and strength, even between cells that were expected to be identical. This contradicts the current notion of gene expression as an orderly sequential and structured phenomenon. These studies seem to indicate that gene expression occurs randomly, throughout the whole genome.

How these cells are still able to differentiate in a predictable manner,…… and perform specialized functions in concert with thousands of other cells,…….. to build a functional multicellular organism, is a mystery to me. And it is enigmatic to the researchers behind these studies as well:

“People are fascinated by how we do what we do despite this noise.” — James Collins


“People ask how come an organism works so well. Perhaps it doesn’t work so well. Perhaps organisms without these fluctuations would outcompete us.” – Johan Paulsson

How the noise came about and why it persists is still somewhat unclear, but benefits from such chaotic conditions may arise from:

1. Controlling randomness (noise) requires a lot of energy, the more chaos the less energy spent. Consequently, only the most critical cellular processes are under tight control, and the rest are more or less random.

2. Expression noise may enable cells to fight off threats. Say a certain level of protein is required to survive a toxic compound attack. Then having cells with sufficient levels of defender protein is more probable in a (noisy) cell population with varying gene expression levels, than in cell populations with a constant level of expression.

3. Randomness may ensure variation in differentiation. An example given in the news feature is the differentiation of blue and green light sensing photoreceptors in drosophila.

So, the noise is there for a reason. Noise, or more precisely – random fluctuation, is an ubiquitous cellular phenomenon. But cells of a given type still end up with similar morphology and similar functionality. The beauty of nature is how the randomness is controlled just enough to achieve the minimum amount of order necessary for preserving functionality. Also, in keeping the random events, flexibility is preserved for future adaptation.

The chaos extends further than gene-expression. If you also consider variations in insertions/deletions, gene copy number and epigenetic differences, the potential for random variation at the gene level becomes evident. To control some of this genetic randomness you have proteins like Hsp90 that masks genetic variation at the transcription level (or folding level to be precise). This is an important control-mode for some of the chaos (DNA sequence variation and mutations) and at the same time it enables sudden exposure of chaos to achieve rapid morphological evolution if needed. I am pretty sure that similar (or very different) control mechanisms will be discovered for gene expression noise in the future.

The noisy expression story is another illustration of how we are not just our genes. The DNA-sequence may be a defining starting point, but there are levels and levels of variation on top of that. As multicellular and evolving organisms, we are constantly balancing between chaos and order. The chaos-level is maximized to minimize energy expenditure and to ensure a multitude of possible paths to follow in an organisms future biological evolution.

The balance is oh so beautiful, it’s called nature.

Hsp90 to end controversies in evolution theory (final chapter, blogging in Just Science 08)

In Uncategorized on February 8, 2008 at 9:42 am

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:

Epigenetic evolution through Hsp90

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.”

Evidence for Hsp90 involvement in rapid evolution of new traits (chapter IV, blogging in Just Science 08)

In Uncategorized on February 7, 2008 at 10:39 am

Previous posts have attempted to demonstrate that there is a potential role for (Heat Shock) proteins that mask mutations, to enable rapid evolutionary changes. The Hsp90 protein has been presented and the basic problems one face to explain bursts in evolution have been outlined. Now the time has come to show real examples of Hsp90 influencing the evolution of traits.

The following are very short summaries of key papers. For details, please see the referenced papers.

1. Hsp90 and Cancer

In 1993 Yang Xu and Susan Lindquist showed that Hsp90 associates with v-src and inhibits its activity in an concentration-dependent manner. Hsp90 was not merely an on and off switch for v-src, but exhibited transient inhibition, dependent on intracellular concentration of Hsp90. This was a clue to understanding Hsp90’s role in cancer (as well as in evolution). After this, many cancer-related proteins have been identified that interact with Hsp90 (see table).

Table from a review in Nature 2005 by Whitesell and Lindquisthsp90-table-2005-review.jpg

The mechanism one speculates, is similar at the molecular level, to the mechanisms postulated for morphological change. Hsp90 stabilizes the otherwise unstable oncogenic proteins, to aid in tumor growth in an environment hostile to tumor development. In other words: the heat shock proteins protects the oncogenic cells from stress. When the tumor cells subsequently attain further mutations and protein alterations, inherent to oncogenic growth, the heat shock proteins are unable to stabilize all of the altered proteins and the tumor can progress into accelerated growth and/or metastasis. The role of Hsp90 in cancer development has been widely accepted and inhibitors of Hsp90 activity is currently undergoing clinical trials for cancer treatments.

2. Drosophila

The key paper on Hsp90 and Drosophila evolution is the Rutherford and Lindquist paper in Nature 1998. This paper has been mentioned on several previous posts here on SciPhu and also in the introductory Just Science post. Again, the take home message is that reducing levels of Hsp90-activity leads to changes in phenotype. The reason for such dramatic effects is probably that Hsp90 stabilizes proteins that are key elements in intracellular signaling pathways. Often these are kinases, phosphatases or transcription factors, see this table for full list. The common feature of these affected proteins is that they regulate the activity of other proteins downstream in the signaling cascade. Thus, changes in the activity of one master protein acts on the stability and function of many other “executive” proteins ultimately resulting in massive changes. The phenomenon has further been elucidated in other species……….

3. Yeast

In yeast, a reduction in Hsp90 levels potentiates drug resistance and this resistance has multigenic determinants working through Hsp90. Hsp90 thus helps yeast evolve to counter the stressful effect of the drug. Interestingly, this effect is diminished by temperature rise. Increasing the stress (by adding heat) therefore, titrates Hsp90 away from the drug-resistance and makes the yeast vulnerable again (could this effect explain why fever has developed ?).

4. Arabidopsis

Evidence for the same mechanisms occurring in plants comes mainly from two publications on Arabidopsis thaliana (Queitsch C et al. and Sangster TA et al.). These images from the latter publication show the extensive morphological changes seen in the plants.

Figure 2. Similar morphological phenotypes of seedlings with reduced HSP90 function by RNAi or pharmacological means (GDA). (a) and (b): purple pigment accumulation; (c) and (d): organ number defect; (e) and (f): narrowly-shaped deformed true leaves; (g) and (h): twisted rosettes; (i) and (j): lobed cotyledon. RNAi plants are T3 generation with from line RNAi-A3. Size bar 2 mm for b and g–i, 1 mm for a, c–f, and 3 mm for normal phenotype. (b) and (f) originally published in [5].

These effects can also be induced by increasing the temperature. Demonstrating the generality in the stress response. Since the genetics of these plants is easier to trace in these plants than in Drosophila or Yeast, the evidence for buffering genetic changes is even more clear-cut in this organism.

An excellent illustration to summarize Hsp90-buffering comes from Sangster TA et al.:


In the last post I will present published models on how Hsp90 can act in evolution, – welcome back for the last post in Just Science 08, tomorrow.

How can chaperones act in evolution (chapter III, blogging in Just Science 08)

In Uncategorized on February 6, 2008 at 11:15 am

Moving away from the specifics of Hsp90 for a while, this post shall focus on the general principle of chaperones in evolution. What supports such an hypothesis:

To begin lets look at the problem of rapid evolution. Darwinian evolution is based on a constant rate of random mutations in the genome of any evolving organism. This implies that mutations happens constantly, by chance, regardless of the external environment. Adaptations consequently arise by chance. Evolution of new traits one may think, is therefore slow and gradual.

Gradual evolution

Gradual evolution (reproduced with permission from Dr. Dennis O’Neil)

Since such a view, does not fit with the bursts of evolution observed in fossil material, alternative explanations have been put forward (see more below). However, even when using a constant random rate of mutations one would expect “bursts” or rapid transitions. This is elegantly illustrated in this simulation of an evolving clockwork. Since a beneficial mutation can have a profound impact on fitness, then there should be no surprise that the transition between av less fit form and a more fit one, happens quickly. Thus even with a constant mutation rate one would probably not see a slow, gradual evolution of species, – basic math skills on exponential growth should make this clear. Why this notion of gradual evolution is prevailing I cannot understand.

In addition there are those that believe that the mutation rate may not be constant. Thus, with an increased mutation rate and rapid transitions one can start to explain the observed bursts of evolution.

Further explaining bursts of evolution we have the theory of ‘punctuated equilibria’, associated with Niles Eldredge and Stephen Jay Gould, which states that organisms go through short periods of rapid evolution from time to time, against a background of relative stasis (see picture below, and this genomicron post as a starting point for more on punctuated equilibrium ).

Punctuated equilibrium
Punctuated equilibrium (reproduced with permission from Dr. Dennis O’Neil, for his tutorials on evolution go here and here).

This has further led to the theory of hopeful monsters. These theories account for non-linear rapid evolution within the boundaries of Darwinian principles, but they have been heavily criticed. One of the main criticisms of these theories, as far as I can understand, is the improbability of a single mutation to give rise to radical morphological changes, and further that this change, if it happens, is most likely deleterious, and if it against all odds is beneficial, its even more improbable that this individual is able to produce offspring with the same trait(s).

So we are still left with some problems: External environment changes can happen really quickly. Is random mutation events, occurring at a slow rate (even if it’s sped up in larger populations or even if monster are hopeful in times of stress), sufficient to explain the effectiveness of adaptations seen in nature ? Does an organism rely on (slow) random mutations to evolve a trait to help the species adapt to the new environment, or are there additional mechanisms in place to speed up this mutation rate and perhaps guide mutation events towards selected genes that allows rapid changes in phenotypes ?

Enter heat shock proteins…….

The hypothesis is the following: If there is a way to mask (deleterious) changes in proteins under normal conditions, one may accumulate such changes without exposing them.

Hsp90 evolution
Illustration from Sangster TA et al. (more on Waddington will follow in the last post).

Thus, with Hsp90 acting as a buffer: one could potentially get a lot of hopeful monsters, under times of stress, as these traits were exposed. This would drastically increase the chances of a beneficial change to occur at the right time. And since the chance of mating with other monsters with similar traits (there are more than one monster, in fact very many), the chance of keeping the trait(s) in subsequent generations is also increased.

Now missing……..evidence, which will follow in the next post.

Presenting….Hsp90 (chapter II, blogging in Just Science 08)

In Uncategorized on February 5, 2008 at 10:44 am

Chapter I gave an introduction into the role of Heat Shock Protein 90 (Hsp90) in evolution. The main point was its ability to mask/hide transforming mutations until needed in stressful times. This chapter describes its physical and biological properties.

Firstly, what the protein looks like. A really good introduction into Hsp90’s structure is found at the Sandwalk blog. Here’s a picture I stole (with permission) from his blog post on Hsp90:

Hsp90 structure
Picture from: Dollins, E.D., Warren, J.J., Immormino, R.M. and Gewirth, D.T. (2007) Structures of GRP94-Nucleotide Complexes Reveal Mechanistic Differences between the hsp90 Chaperones. Molec. Cell 28:41-56.

From Sandwalk: The complete protein is a dimer of two identical subunits. Each monomer has three distinct domains; an N-terminal domain (N); a middle domain (M); and a C-terminal domain (C). The ATP hydrolysis site sits at the interface between the N and M domains. The C domains interact to form the dimer. The presumed site of binding for misfolded proteins (“client” site”) is in the V-shaped pocket formed when the C domains come together. The mechanism of action of Hsp90 proteins is not known although it presumably involves a conformational change induced by ATP hydrolysis.

Secondly, it’s mode of action. Hsp90 works in concert with many other proteins to form protein-complexes ultimately activating the target protein. The molecular mechanism is as mentioned, still unresolved despite the presence of crystal structures. However, the following illustrations are taken from The Jackson Laboratory at University of Cambridge UK, to depict the overall events:

Model of the activation of a client protein by chaperone machines.
The chaperone Hsp70 system targets the client protein, in this case the steroid receptor, to the Hsp90 chaperone via the organising protein HOP which binds both chaperones. After transferring the steroid receptor to Hsp90, Hsp70 dissociates and is replaced by co-chaperones such as p23 and the high molecular weight immunophilin FKBP52. It is only in this complex that the steroid receptor is activated to bind ligand with high affinity.


And thirdly, which proteins does Hsp90 interact with. Again from The Jackson Laboratory:

Hsp 90 and Proteins it interacts with.
The abundant protein Hsp90 is thought to assist in the activation and assembly of specific proteins. Many of these proteins are critical for signal transduction and cell division. As a result, Hsp90 is a target for anti-tumour drugs.

Other examples are: PDK1, PKC-gamma, vSRC/cSRC, PPAR-alpha and p53. A comprehensive list of interacting proteins compiled by Picard Laboratory can be found here.

Thus, looking at all the proteins that can be affected by Hsp90, there is no surprise that the protein is highly conserved and that effects are profound when Hsp90 is fiddled with.

Revolution Evolution (chapter I, blogging in Just Science 08)

In Uncategorized on February 4, 2008 at 10:01 am

My contribution to JustScience 2008 will be a review on a protein with the potential to transform evolution theory as we know it today. The review will be divided into 5 separate blog posts:

1. Introduction to Hsp90 and evolution (this post)

2. Presenting the Hsp90 protein

3. How can chaperones act in evolution

4. Evidence for Hsp90 involvement in rapid evolution of new traits

5. Summary

Here’s the teaser: In one generation you can go from this

Drosophila wild type

to this (a hopeful monster ?).

Hsp90 reduced expression in drosophila
(from Rutherford SL and Lindquist S, Nature 1998
, to see more “monster”-pictures, do a google image search on Hsp90 and evolution)

The protein in focus, Heat Shock Protein 90, is otherwise as normal as a protein can get. It is ubiquitously expressed in all cells and across species, and its function is the same as other heat shock proteins, it’s a chaperone.

A chaperone is a protein that helps other proteins fold correctly (or prevents them to aggregate into non-functional protein junk). Without the chaperone the protein would not achieve an active conformation and end up being degraded. For an excellent video illustrating chaperone assisted protein folding go here.

Caperone illustration
Illustration of chaperones in action. Picture from Nurse Minerva

Now, it turns out that the Hsp90 chaperone function is important for development and evolution of new traits. To illuminate this, the first paper I will discuss is from 1998 by Susan Lindquist’s lab at the Whitehead Institute.

In this paper they take fruit flies and reduce the expression of Hsp90. As I shall come back to later, this is the experimental equivalent to a stressful condition (like for instance high temperature). They can’t knock out Hsp90, because a complete lack of it is not compatible with life (which demonstrates the importance of this protein). When Hsp90 levels are reduced, the fruit flies are born with a number of different defects ranging from defects in the legs and bristles to defects in the eye (see image above). Now, this could be expected when knocking out a protein, but such extensive morphologic changes are not expected from just reducing the levels of a protein (unless maybe if it’s a transcription factor, which it isn’t). The hypothesis explaining this goes as follows……Since Hsp90 is a heat shock protein it is helping other proteins fold. When stressful conditions occur, there will be more proteins that are in need of folding-help, thus some of the proteins that under normal conditions got their help from Hsp90 will now be left on their own. Since, under such conditions, you see these extensive morphological changes, these proteins must be doing something out of the ordinary when on their own, or if they aggregate, their absence causes abnormality. The theory states that these in-need-of-help-proteins must have accumulated mutations that potentially causes abnormality, but under normal conditions they are still able to perform normally due to the action of Hsp90. The implications for evolution are breathtaking since this means that an organism can accumulate a number of mutations and still function normally, but when exposed to stressful conditions, the changes at the protein level are suddenly exposed in their offspring and appear as physical abnormalities. This allows for extremely rapid evolution and could potentially enable a species to change in just a couple of generations.

Illustration of the process and further evidence for this theory will be presented in the next 4 posts the next 4 days, in SciPhu for just science 08.

On ScienceBlogs 27/-1-08: Quick-Change Evolution

In Uncategorized on January 27, 2008 at 9:46 pm

I have so much to learn, and I’m looking so much forward to learning it. This time around it’s in evolution theory, and I’m going to make some bold statements while learning.

Some recent posts here on SciPhu has been on Hsp90 and rapid morphologic evolution. On ScienceBlogs the topic of the day is Quick-Change Evolution. The background is a blogpost by Olivia Judson stating the return of the hopeful monster. The hopeful monster theory says that extensive morphologic changes in one individual offspring (a monster – an individual organism looking radically different from the rest of its species), sometimes creates beneficial features enabling the monster to create further offspring with similar features. In this way one can achieve rapid evolution (as short as one generation) into the beginning of a new species. The theory is a controversial one and is also called punctuated equilibrium. I however, am apparently at odds with most science bloggers and evolutionary biologists, since the hopeful monster theory sounds plausible to me. How is this linked to Hsp90 you may wonder. Well…

Knocking down Hsp90 creates rapid morphological changes from one generation to the next (for details see references in my previous posts Evolution too fast for our genes to follow, On Hsp90 and morphological evolution and The rate of evolution/mutation/adaptation and future posts to come). Hsp90 does so by masking mutations under normal conditions and then revealing them under stressful conditions. Just to repeat myself, – this concept suddenly made evolution comprehensible to me, and I do not understand why other scientists haven’t embraced the masking concept as a revolutionary concept, expanding darwinian evolution theory.

Now it’s dawning on me why…….Such masking of mutations to produce a pool of potentially crucial mutations gives support to the hopeful monster theory.

One of the main criticisms of this theory, as far as I can understand, is the improbability of a single mutation to give rise to radical morphological changes, and further that this change, if it happens, is most likely deleterious, and if it against all odds is beneficial, its even more improbable that this individual is able to produce offspring with the same trait(s). But…..

Extensive morphological change has been shown to happen due to single mutations, and…

With Hsp90 as a player in the game, it need not be a single mutation, but rather a pool of mutations already present and waiting to be exposed under stress. That increases the chances of achieving multiple changes in multiple individuals. Consequently the chance(s) of producing one or more beneficial trait(s) is(are) increased.

In addition, if such stress appears and mutations are revealed, then many individual offspring will have extensive changes, and the chances for two such individuals to mate increase dramatically.

Thus, I cannot see why a combination of the hopeful monster theory and the actions of Hsp90 (and possibly other mutation masking proteins) under stressful conditions, is a perfectly credible extension to darwinian evolution. An extension that can explain some of the rapid changes that has occured during evolution of species.

The rate of evolution/mutation/adaptation

In Uncategorized on January 3, 2008 at 1:48 pm

I came across this blogpost from evolgen which is a part of a discussion with John Hawks on increased rate of evolution. It seems to me that the term “neutral mutation” is central in this discussion. However, looking at the effect of Hsp90 as described in my previous posts (and future posts to come), – is it possible that some of these “neutral” mutations aren’t neutral at all, but rather deleterious or beneficial mutations masked by a heat shock protein ?

I am in over my head when it comes to in-depth analysis of population genetics data, but still, to me, – the action of mutation masking Hsp’s (if this is truly a valid evolutionary phenomenon) may seem to bridge these two opponents as well as solving a lot of other controversies surrounding the rate of molecular evolution vs. phenotypic/morphological evolution.

Evolution too fast for our genes to follow

In Uncategorized on December 20, 2007 at 1:41 pm

In the near future, the upcoming posts will center on Heat shock protein 90 (Hsp90) and how the function of this particular protein can explain rapid morphological evolution, or rapidly evolving phenotypic variation if you will. The topic and papers on it, are in my opinion hugely underrated. To me, until these papers came out, the extremely rapid (in a cosmic timescale) change in physical appearance that is seen in the evolution of species, was the major (only ?) valid argument contradicting Darwinian evolution through random mutations and genetic drift. This because genetic drift through random or even guided mutations, is just too slow to explain the evolution of such a vast spectrum of species as the one present on earth, in such a (relatively speaking) short time. The concept of masking mutations through the action of Hsp90 was an eye-opener and presented me with an extension to genetic evolution that explained rapid phenotypic change. Thank god(!) for this possible counter argument towards the missing link babble presented by creationists and their like. And it is surprising that these papers haven’t been used more in discussions concerning evolution. More details on Hsp90 to follow, but the fundamental paper is (not open access unfortunately): Hsp90 as a capacitor for morphological evolution Nature 396, 336 – 342 (26 Nov 1998).