On BioScience and Life and Such

Archive for December, 2007|Monthly archive page

On Hsp90 and morphological evolution

In Uncategorized on December 21, 2007 at 12:05 pm

As a further introduction into Hsp90 and its role in evolution, here are two segments cut from this review:

1. “Because signaling proteins with multiple regulatory states often undergo a conformational switch, the structural flexibility needed for these steps may render them inherently less stable and thus more likely to be recognized by Hsp90. On the other hand, under stress conditions such as heat shock Hsp90 contributes more generally to the refolding of denatured proteins (Nathan et al., 1997). Although the exact structural features recognized by Hsp90 are not yet understood, the exposure of these features to Hsp90 is likely a result of intrinsic or stress-induced structural flexibility. Thus, interactions of substrate proteins with Hsp90 arise from structural properties at the molecular level rather than biological function.”

2. “Defects in cell physiology caused by Hsp90 disruption can lead to defects at the level of tissue and organism. Interestingly, recent work connects Hsp90 function with morphological evolution, a process that often requires the effects of independent genetic changes (Rutherford and Lindquist, 1998). Hsp90-null mutants are lethal in eukaryotes, but surprisingly partial disruption of Hsp90 in Drosophila by a temperature-sensitive mutation or low amounts of GA shows a wide assortment of heritable phenotypic variations. The variations may arise from alleles of proteins, which depend on the full function of Hsp90 as a conformational buffer to maintain “wild-type” activity but whose phenotypes can be stabilized by other genes following selection. By extension, polymorphisms in all of the proteins participating in an Hsp90-dependent signaling pathway should be buffered by Hsp90 function. In the wild, overloading of the Hsp90 “capacitor” with denatured proteins under environmental stress could similarly increase the phenotypic diversity on which natural selection and ultimately evolution acts (Rutherford and Lindquist, 1998). Hsp90 with its connection to the cellular signaling network may be particularly suited to such a function. Thus, the mechanisms of chaperone-mediated protein folding at a molecular level can be integrated with cellular processes and with the development of organisms and species.”

Thus, if I understand this correctly: Under stressful conditions the Hsp90 is titrated away from its normal substrates exposing structural variations otherwise masked. Seeing that many of these normal substrates are signaling proteins (and thus affects many other proteins) this potentially, leads to extensive variations in phenotype.

More to follow


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).

Clarifying Misuse of Science

In Uncategorized on December 17, 2007 at 2:53 pm

Just to expand a little on the subject, in our previous post, of misusing science. There are two ways of misusing (abusing ?) science. The first is twisting scientific facts to fit ones own agenda. The other and more immediate, way of misuse is achieved when ethics is left behind in practical applications of science. Prenatal testing for familial hypercholesterolemia is sad recent example of the latter.

Richard Dawkins beeing clever on hindsight

In Uncategorized on December 14, 2007 at 10:14 am

Something that should strike anyone reading, or listening to, Dawkins arguments against religion is: Beeing clever on hindsight is always easy.

It is easy to see that God and religion are delusions (or faith as one might call it) knowing what we know today. Throughout history however, alternative explanations to existence has been sparse or non-existent and religion has been the best explanation anyone has been able to come up with. Consequently all known societies has had one or more Gods. Religion has been at the root of building society as we know it today, including the flaws.

Today, science builds society more than religion does, – and increasingly so. Science is therefore at risk of becoming the new religion, and Dawkins may be destined for one of the new Archbishops. We should all learn from the history of religion and avoid the pitfall of discrediting and ridiculing what we cannot explain or things we cannot find supporting evidence for. What science cannot explain today, including any superhuman beeing or force, is not necessarily wrong to believe in, and explanations or evidence for some kind of a God may appear in the future when scientific knowledge explains the currently hidden details.

Instead of concluding the obvious (that God is a delusion), we should take Dawkins arguments as strong documentation for the continuing misuse of religion to opress and abuse. This misuse is not due to faith in itself, but rather blaim should be put on the people claiming religious leadership and authority. These peoples actions are probably more a result of darwinian principles (as the struggle to excede other members of a population, – through oppression or otherwise, is a fundamental darwinian principle), than they are results of religious faith.

This last point is important to remember because science will inevitably be misused the same way, and we as scientist are obliged to fight back.

The need for restraint

In Uncategorized on December 12, 2007 at 1:32 pm

Overselling Science is probably the biggest threat to scientific credibility, nevermind cheaters like Hwo Suk Hwang or even intelligent design. These are obvious and passing threats, easy to neutralize. Rather, do mind genetic genealogy companies telling you they can find your extended family (when what they actually find is your haplogroup), personal genetics companies telling you about your lifestyle and disease risks (when these risks are low and penetrance is uncertain), – and mind greatly: dating companies telling you they can find your match based on your DNA-profile.

We are moving in the right direction, let’s not screw it up for ourselves.


In Uncategorized on December 11, 2007 at 1:52 pm

Normal is variation, no exception.

Pharmacogenetics and Normal Variation

In Uncategorized on December 10, 2007 at 8:29 am

Argument: Doing pharmacogenetics is futile since the frequency of clinically relevant genomic variations does not differ between the patient population and the normal population.

Reply: Since the frequency of most of these genomic variations is high, you would need a large cohort to verify that no over-representation exists in your patient samples. In addition, a negative answer (no variation detected) is not the same as a useless answer, as it can be used to look for other reasons for the condition presented.

Premature Launch 071207

In Uncategorized on December 7, 2007 at 12:54 pm

This is the premature launch of the SciPhu weblog. This blog will hopefully, become a communication channel for the upcoming SciPhu community.