On BioScience and Life and Such

Posts Tagged ‘evolution’

Correct me if I am wrong

In Uncategorized on March 19, 2014 at 12:54 pm

Background: The Hyperion Cantos book 1 and 2  and The New York Times on mitochondrial manipulation (see further description on bottom of page).

It is my impression that theres an underlying, and absolute, assumption that genetic engineering will lead to less diversity.


If given a choice of a range of possible engineered enhancements, would all societies, ethnicities and subgroups have the same preferences ?

I think not.

Then it follows that future genetic engineering will lead to greater diversity. Strange and unpredictable diversity.

The difference would be that it is now humankind deciding which different variants that are brought to life, not “nature”.

We would still need to accept and accomodate the “different” individuals in our society, probably even to a greater extent.

Would that not be a good thing ?

If you keeep putting up hurdles to stop implementation of advances in genetic engineering, are you not halting the development of a “natural” way to save humankind in the future ?

Genetic engineering is by this reasoning, the natural way forward.

It should be cool an unpredictable, just like nature is today.

The Hyperion Cantos book 1 and 2 describes a struggle between three parties: 1) artificial intelligence (AI), 2) a probable extension of our present tech-savvy society dependent on AI and 3) an AI-independent “natural” biologically diverse society (based on genetic engineering !?). Spoiler: The “natural” biological society wins.

Quote from NYT-article: “Some told the officials that the technique could introduce new genetic mutations into the human gene pool. Others warned that it could be used later for something ethically murkier — perhaps, said Marcy Darnovsky, executive director of the Center for Genetics and Society, “to engineer children with specific character traits.””

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Tidbits from the www that makes you think

In Uncategorized on January 24, 2013 at 9:25 am

From a comment on a post on my friendfeed (I hope its ok that I quote this from you Kamilah Reed):

This makes me think of the mantis oothecae that I saw the mother lay on the edge of our deck. I saw her stand guard there until the cold killed her. The egg cases still out there, toughing it out through all this nasty cold weather. I can’t wait to see if we’ll actually have dozens of baby mantises next year. We’ve had them before, but I didn’t see where the case was last time.

I recently finished The Social Conquest of Earth (recommended), and found myself buying into Edward O. Wilsons arguments on social evolution vs. kin selection. We have become social beings based on traits like compassion of and empathy with, other individuals of our kind.

Based on th quote above though, you might want to expand the reach of those human traits to include other species as well. This quote encompasses empathy, compassion and sympathy towards a species far removed from our own. Importantly, a species I do not particularly care much about myself. Without the particular context of the story, I would gladly have gotten rid of those eggs, but since I find myself intrigued by the sacrifice of the mother-Mantis, I probably wouldn’t.

So, to all of you out there dooming the human race, despair not, – there may be hope. There are individuals out there that will share stories and facts that saves us – be thankful for diversity and keep listening.

Mantis religiosa trademark

Mantis religiosa trademark (Photo credit: macropoulos)

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Junk, DNA, RNA, Brain, Biology and Possible Solutions

In Uncategorized on September 11, 2008 at 10:10 am

We and all other organisms are complicated biological structures made from very simple building blocks on an information template of DNA. Individual variations in DNA are rather easy to work out although you do need lots and lots of DNA sequencers, data-storage facilities and data comparison programs. Fact remains, – you basically only need time and money to do this.

We know that the DNA sequence itself is diverse enough to make every individual exclusive while retaining enough common features for speciation. So, DNA explains a lot, but the final functionality including the ability to adopt to changing environments, depends on the next levels of variation…

Take the Necker Cube below. As described by  Edge writer Nathan Myhrvold:

This is a perfectly good 2D picture, but we cannot help trying to force into being a 3D object. The 3D reconstruction problem is ill posed—there are two very different solutions, each of which is feasible. So, when you look at it you alternately see one then the other—you can feel it pop in, or pop out. Without a unique solution your brain flips between the possible solutions.

The analogy to biology is as follows:

Strictly speaking, the cube is two-dimensional. But, for all practical purposes it is a three-dimensional object. At the same time it’s three dimensional form shifts from one confirmation to the other.

The analogy to DNA is that while the written DNA-sequence is linear (two-dimensional) the resulting molecular three dimensional structure allows for transcription into RNA and interactions with proteins both at the DNA and RNA level. These interactions in turn can lead to effects that vary depending on the surrounding environment. The Necker cube is made out of 12 identical lines giving rise to two different three dimensional conformations. DNA is made out of four versions of millions of basepairs. Resulting in a vast number of possible final variations of effects.

Biology handles a chaotic and changing environment using simple building blocks to make flexible, hyper variable, intricate and complicated possible solutions. Knowing the DNA-sequence, the transcriptome and the proteome is basically just discovering the two first dimensions in a many-dimensional organism.

New ideas, approaches and tools are needed to explain how this seemingly chaotic system works. Dismissing reasons for the obvious complexity using terms like “junk-DNA” is not going to get us anywhere.

Instead, let’s start by acknowledging that we know very little. All we know is that function comes out of an apparent chaotic mixture of DNA protein and RNA. Let’s speculate that everything is there for a reason. Without reason you loose hope and visions and those are qualities that science is vitally dependent upon.

Illustration taken from http://wisebytes.net/illusions/

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).

Richard Dawkins: an Evangelical atheist ?

In Uncategorized on April 14, 2008 at 1:07 pm

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

Knowing what we know today, it is easy to see that God and religion are delusions (or faith as one might call it). Throughout history however, alternative explanations to existence has been sparse and religion has simply been the best explanation around. 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 (including the flaws) 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 currently cannot find supporting evidence for. What science cannot explain today, including any superhuman being or force, is not necessarily wrong for believers to believe in, – and who knows, evidence for some kind of a God may appear in the future when science has advanced further.

John Gray writes in “The Atheist delusion

“Zealous atheism renews some of the worst features of Christianity and Islam. Just as much as these religions, it is a project of universal conversion. Evangelical atheists never doubt that human life can be transformed if everyone accepts their view of things, and they are certain that one way of living – their own, suitably embellished – is right for everybody. To be sure, atheism need not be a missionary creed of this kind. It is entirely reasonable to have no religious beliefs, and yet be friendly to religion. It is a funny sort of humanism that condemns an impulse that is peculiarly human. Yet that is what evangelical atheists do when they demonise religion.”

Instead of concluding the obvious (that God, as explained in the bible or elsewhere, is a delusion), we should take Dawkins’ writings as strong documentation for the continuing misuse of religion to oppress and abuse. The misuse is not caused by faith or religion in itself, but rather by people claiming religious leadership and authority. Their 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 conscientious scientist are obliged to fight back.

This post is an update from the previous post: Richard Dawkins being clever on hindsight

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.

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.


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