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Directed evolution?

Trying2Bopen

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Sep 27, 2006
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I was asked in an oral examination this past week by an ecology prof:

“If an organism is shown to produce more beneficial mutations under stress, would that still be considered natural selection?”

I didn’t know how to answer the question and made something up that was probably wrong.

After the exam my prof explained to me that there are researchers attempting to demonstrate that bacteria produce beneficial mutations more frequently when stressed as a way to produce offspring that will be less stressed under the same situation. Does anyone know anything about this, and would it still be considered natural selection?
 
Your professor is playing games of semantics, not science.

The 'natural' in natural selection doesn't refer to lab setting vs wilderness. It seems to be a trap to see in which sense you take the word. To quote the wiki (because I'm too lazy tonight to write my own explanation), natural selection is whenever it is observed that:

In each generation, only some individuals will produce offspring themselves, and of those that reproduce, some will leave more offspring than others. This is seen as the "natural" process of reproductive selection.
.

So assuming that some bacteria produced more offspring than others, they were selected for, and thus were an example of natural selection.
 
My guess that "stressing" an environment would create more mutagenic factors, which could, statistically speaking, create species that are better suited to the said enviroment.

But it's also statistically possible that the whole system could fail and no species that have adapted to their new environment would arise.
 
If an organism is shown to produce more beneficial mutations under stress, would that still be considered natural selection?”
Sounds like a trick question. Organisms do not "produce...beneficial mutations..." Mutations occur that may or may not be beneficial but they are not under the control of the organism that produced them.
 
No, there is a contingent of scientists out there that are investigating the possibility that bacteria produce disproportionally beneficial mutations. For example, if you heat your bacteria, you will get more heat-loving offspring than if you freeze your bacteria. It has by no means been proven to be possible, but it certainly is intriguing.

I'm by no means an expert, but I think some people that post here know some things about it.
 
No, there is a contingent of scientists out there that are investigating the possibility that bacteria produce disproportionally beneficial mutations. For example, if you heat your bacteria, you will get more heat-loving offspring than if you freeze your bacteria. It has by no means been proven to be possible, but it certainly is intriguing.

I'm by no means an expert, but I think some people that post here know some things about it.

Hi Christine, that sounds really interesting. I was aware that some bacteria have to ability to alter the mutation rate under stressful conditions (perhaps by failing to repair damage as quickly?) and that this can lead to an increased rate of evolution, but I wasn't aware of this.

Sounds interesting and I'm looking forward to hearing more. I'm still a little skeptical, as I wonder what sort of mechanism would be involved, but it sounds like a really exciting area of inquiry.
 
Okay, I did a little back ground work and talked to my prof. What we are talking about is referred to as “directed mutation” and was first proposed by J. Cairns or Harvard U back in 1988. Results from his experiments suggest that bacteria under a certain type of stress are able to somehow “induce” more beneficial mutations in genes that will allow their offspring to better deal with the same stress….

Online reading suggests that the debate is "raging" and a popular idea now is that a higher rate of mutation (both good and bad) may occur for some individual bacteria and only the beneficial mutants in future cohorts are observed because all the others died. But this info is not from a creditable source at all…
 
Results from his experiments suggest that bacteria under a certain type of stress are able to somehow “induce” more beneficial mutations in genes that will allow their offspring to better deal with the same stress…

I don't think the bacteria are 'willing' anything to happen here. It seems entirely reasonable to me that certain forms of stress would increase mutation rates since it is quite reasonable to assume that stress could affect the DNA replication reaction. However I cannot see how the DNA replication could be affected in such a way as to bias only beneficial mutations. What is beneficial cannot be known until the organism is tested against its environment.
 
However I cannot see how the DNA replication could be affected in such a way as to bias only beneficial mutations.
Bacteria have probably seen most forms of stress that can ever happen many, many times. Why couldn't they have a feedback mechanism from the environment in to their genes? It might sound Lamarckian but if you google "epigenetics" you'll find there is some evidence for subtle Lamarckian style feedback.
 
bacteria under a certain type of stress are able to somehow “induce” more beneficial mutations in genes that will allow their offspring to better deal with the same stress….

This is tricky. As a control, any identified "beneficial' mutations must be shown not to exist genetically, not just as a lack of physiological manifestation, before the application of stress. Natural slection has a way of illuminating what was already there.
 
Bacteria have probably seen most forms of stress that can ever happen many, many times. Why couldn't they have a feedback mechanism from the environment in to their genes? It might sound Lamarckian but if you google "epigenetics" you'll find there is some evidence for subtle Lamarckian style feedback.

Would this not imply that there is information encoded in the bacteria's DNA that essentially lays out 'survival plans'? If so surely they are merely 'switching' tactics rather than creating new ones?
 
allow me, as an old Microbiology and Bacteriology major to shead a little light on the subject. In additon to the bacterial genome are little recombinant-prone pieces of DNA called plasmids. The are very promiscuous and can even move inter-species (that is, E. coli to say, a Nisseria sp.) Replication time is around 20 minutes, so mutations can arise fairly fast. Bacteria that can't handle the stress die, those with the gene can produce plasmids and pump them out into the environment. They can be taken in by other bacteria with Pili or trough endocytosis. Sort of a feedback. That's the really simplified process, but then again, it's been 16 years since I worked in the field (my babies, Mellitangium boletus!) When in doubt check out Davis and Dulbecco "Microbiology", the bible of the university micro course.

Basilio
 
Would this not imply that there is information encoded in the bacteria's DNA that essentially lays out 'survival plans'? If so surely they are merely 'switching' tactics rather than creating new ones?
Yes. Basically I'm proposing there are inactive genes that are marked for reactivation when a certain stress occurs. Or there are genes that are marked for repetition when a stress occurs. The mechanism could presumably have a lot in common with the known expression mechanism.

I'm not insisting this mechanism actually exists. I'm justing saying there are conceivable mechanisms.
 
I was asked in an oral examination this past week by an ecology prof:

“If an organism is shown to produce more beneficial mutations under stress, would that still be considered natural selection?”

I didn’t know how to answer the question and made something up that was probably wrong.

After the exam my prof explained to me that there are researchers attempting to demonstrate that bacteria produce beneficial mutations more frequently when stressed as a way to produce offspring that will be less stressed under the same situation. Does anyone know anything about this, and would it still be considered natural selection?

I may be wrong about this, and someone please correct me if I am, but my understanding is that evolution comes in two fundamental pieces:

  • Mutation - The random changes made by an organism
  • Natural Selection - The non random circumstances of the environment which affect the organism's reproduction
So an increase in mutation rate is not a change in natural selection since natural selection is a force of the environment and the bacteria is not changing that. The bacteria may be attempting to compensate for a more stressful environment, but that's still mutation, not natural selection. So my answer would be NO, changing your mutation rate will not change the environment's selection pressure.

Example: Suppose the environment is becoming dry (or at least less wet). Natural selection favors bacteria that are more tolerant of arid conditions. This (supposedly) causes the bacteria to start mutating faster to try and find some form that doesn't dessicate so easily. No matter the mutation they come up with, the selection criteria remains fixed: unless you can tolerate low humidity, you lose the game.
 
I was really hoping someone who knows what she/he is talking about would have come by by now and helped me out. Anyhow the idea is that mutation mechanisms themselves may have evolved. That is, that if you apply a specific stress (like heat) some organisms may have areas of genetic material that is particularly sensitive to heat. If these areas also happen to be responsible for heat regulation you are likely to get larger numbers of heat tolerant offspring.

Normally you would expect that you would get equal numbers of offspring that are less heat tolerant, but this isn't necessarily true. You might get offspring that are completely unviable, offspring that have no meaningful differences, offspring with random features that may or may not be beneficial but no cold tolerant offspring.

This would have to depend on the mechanism used for tolerating the heat obviously. If you can imagine something that makes it easier to tolerate heat, has nothing to do with tolerating cold, and has no downside other than being wasteful AND you can imagine that the genes that control this mechanism are particularly likely to mutate when stressed by heat, then you've got it.
 
I may be wrong about this, and someone please correct me if I am, but my understanding is that evolution comes in two fundamental pieces:
  • Mutation - The random changes made by an organism
  • Natural Selection - The non random circumstances of the environment which affect the organism's reproduction
So an increase in mutation rate is not a change in natural selection since natural selection is a force of the environment and the bacteria is not changing that.

Yes, I think the problem arises with the assertion that beneficial mutations occur at a higher frequency then would be predicted by random chance. Thus, mutation does not appear to occur at random within a population, making supposition 1 or your statement untrue…

Okay, now that I am done with all my exams and back to being a normal insomniac, I have been sleuthing a bit and found the abstract from the original paper published in Nature in 1988:

The origin of mutants
John Cairns, Julie Overbaugh & Stephan Miller
Department of Cancer Biology, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA
Nucleic acids are replicated with conspicuous fidelity. Infrequently, however, they undergo changes in sequence, and this process of change (mutation) generates the variability that allows evolution. As the result of studies of bacterial variation, it is now widely believed that mutations arise continuously and without any consideration for their utility. In this paper, we briefly review the source of this idea and then describe some experiments suggesting that cells may have mechanisms for choosing which mutations will occur.
This paper founded the idea of the directed mutation hypothesis. Here is an abstract from another paper from Nature (1990) holding a contradictory view:

New data on excisions of Mu from E. coli MCS2 cast doubt on directed mutation hypothesis
John E. Mittler & Richard E. Lenski
Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92717, USA
ACCORDING to the directed mutation hypothesis, certain mutations in bacteria occur more frequently in environments in which the resulting phenotype is selectively favoured than in non-selective environments1–4. This hypothesis therefore challenges the fundamental tenet that mutations occur spontaneously, irrespective of effects on the organism's fitness5–9. One purported case of directed mutation is the excision of a Mu sequence from Escherichia coli strain MCS2 in minimal lactose-arabinose medium1,2. Here, we show that this case can be more simply explained by an accelerated rate of excision mutation in response to non-specific physiological stresses of starvation and by slight growth of MCS2 on minimal lactose–arabinose medium.
So it looks like it may just be a more stress = more mutation situation. But I am still finding papers on both sides of the argument…
 
Take a look at James Shapiro's work, at http://shapiro.bsd.uchicago.edu/index3.html?content=publications.html .

There were a series of papers in the mid-90's on adaptive mutation, and a more recent overview at http://shapiro.bsd.uchicago.edu/Shapiro_1999_Genetica.pdf .

I bit of a sidenote - I communicated briefly with Dr. Shapiro a few years back. He was quoted as stating:
There are no detailed Darwinian accounts for the evolution of any fundamental biochemical or cellular system, only a variety of wishful speculations.
.

I'm not sure where the original is from the the quote was used by anti-evolutionists to attack evolution in general (see, for example, http://www.leaderu.com/orgs/arn/behe/mb_dm11496.htm, about 2/3 down.) I thought this quote was taken out of context; his work on adaptive evolution is still evolution.

Dr. Shapiro was simply stating that there may be non-Darwinian mechanisms underlying evolution, IIRC.

That may be what your professor was trying to ask - is non-Darwinian selection still evolution? Can mutations be selected before reproduction?

Patricia Foster is another name that comes up a lot with this (I think she collaborated with Cairns) - see http://www.bio.indiana.edu/facultyresearch/faculty/Foster.html, as well as Susan Rosenberg at http://imgen.bcm.tmc.edu/molgen/facultyaz/rosenberg.html
 
That may be what your professor was trying to ask - is non-Darwinian selection still evolution? Can mutations be selected before reproduction?

This mechanism would have itself had to evolve via traditional Darwinian mechanisms of natural selection, right? So the ability to induce greater numbers of beneficial mutations under stress is like any other evolved mechanism.

But from reading it sounds like a subset of the bacteria population switch mechanism for transcribing DNA when stressed- they switch to a more error prone system, right? They are not switching to mechanisms that produce more beneficial mutations, just more mutations. So no ghost of Lamarck after all. Do I have this right?
 
This mechanism would have itself had to evolve via traditional Darwinian mechanisms of natural selection, right? So the ability to induce greater numbers of beneficial mutations under stress is like any other evolved mechanism.

But from reading it sounds like a subset of the bacteria population switch mechanism for transcribing DNA when stressed- they switch to a more error prone system, right? They are not switching to mechanisms that produce more beneficial mutations, just more mutations. So no ghost of Lamarck after all. Do I have this right?

From what I've read, yes. Highly stressful environments induce error prone transcription processes (and seem to inhibit DNA repair), which naturally increases mutation rates. I find it very hard to believe they somehow get more 'good' mutations then 'bad' ones. It's just, often, very hard to find the 'bad' ones becuase they've already died.
 

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