You know, Lamarck was given a bad rap. That stupid experiment with the tails of mice did not disprove anything. The mice did not want/desires/strive/need cut off tails. if you actually read his theory, what he says is: that an animal, by stiving to change, can change and pass this on. Ie, an animal can 'self-direct" it’s own DNA mutations. Totally different from passing on characteristics aquired from EXTERIOUR sources. Personally, I doubt that this is a major engine in evolution, but it might very well be one of them. Why not? It would be VERY useful.
Dr. Lao:
No, the mutations I refer to are seemingly random, i.e. the SOS response.
There is one interesting case that I found on line (I’ll try to find a link,) where on one particular island fruit fly had adapted to eat a fruit toxic to all other species. They did this in a very short time from their introduction to the island. This was also the only change found between these flies and other fruit flies. THe specificity and rapidity of the change was unexpected.
Again, in the lab tests the mutations were, like the bacteria, random. THe intriguing thing in both the experiments (to me anyway,) was that the organisms raised their mutation rates in the first place.
If you think about it, a lot of small, random mutations have a better chancing of combining synergistically to create a needed adaptation than a slow steady state of larger random mutations. That’s what I mean by mutation “seeking” an adaptation. I apologize. It’s hard not to anthopomorphize.
I said:
“There is one interesting case that I found on line (I’ll try to find a link,) where on one particular island fruit fly had adapted to eat a fruit toxic to all other species. They did this in a very short time from their introduction to the island. This was also the only change found between these flies and other fruit flies. THe specificity and rapidity of the change was unexpected.”
My apologies. I haven’t had my coffee yet, and I got the gist of the article completely wrong. It doesn’t have much to do with what we are talking about, but is interesting nonetheless. I wish I could read the original paper the article is based on.
Here’s the link:
http://www.eurekalert.org/releases/roch-abm090998.html
another:
http://cas.bellarmine.edu/tietjen/Ecology/size_matters.htm
This is cute:
http://www.exploratorium.edu/exhibits/mutant_flies/mutant_flies.html
Scylla: A question which I think many of us have on this issue (or maybe it’s just me; I can be pretty dense sometimes) is whether the ‘mutations’ seen in the flies you mentioned (I know we’re stuck on flies, but this is all we have, example-wise) are genotypic, that is, the genes themselves have changed, or phenotypic, that is, the expression of the genes is different, but both generations of flies are essentially the same genetically (aside from the background mutations that both the experimental and control groups should experience). This is really the key to determining whether this is something truly fascinating or something rather ‘mundane’ (still fascinating, though more easily explainable, I should perhaps say…). I’m not trying to be snide or anything, but some clarification would go a long towards understanding 
I really don’t know the answer Mauve Dog, sorry. My impression is that random mutations increased.
DO the mutations we normally see in fruit flies like white heads, or extra legs come from within the genome, or outside?
The article (from the Op) stated specifically that the cold-weather gene was thought to exist within the genome of the fly but only activated in the subsequent generations.
In other circumstances of stress, their mutation rate increases (random mutations.) My take on the article was that this increased mutation rate was a response by the fruit fly population seeking a synthesis of traits that would provide a useful adaptation.
BTW: I’m leaving for vacation soon. Should be back by Tuesday.
Whoa, I have experience. I suppose that’s what 2 years in med school and 2 in grad school bring. If you are ever in Houston, I’d be glad to show you around a fly lab (and go up to meet Susan, she’s really nice).
The way adaptive mutation was found in E. coli is fairly lucky, really. They took bacteria who could not metabolize lactose in agar and put the gene to metabolize lactose (it codes for the enzyme lactase) into the bacteria on a little bit of extrachromosomal DNA called a plasmid. The lactase gene on the plasmid had a nonsense mutation. The whole gene had a +1 frameshift for you biology types. For you non-biology types, this is the equivalent of adding a letter to make the sentence THE FAT CAT RAN into ZTH EFA TCA TRA N.
Well anyway, the bacteria still couldn’t eat lactose, so when put on agar plates in which the only source of carbon was lactose, they starved. Funny thing was, after a few days, some bacteria started to grow. Problem with this are
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The bacteria aren’t growing so they weren’t replicating DNA, which is thought to be the major source of mutation.
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It happened more frequently than regular bacteria who were growing.
So, research ensued.
It turns out that this plasmid was preferentially mutated. Now people got really excited – was this directed? I believe the evidence so far is that it wasn’t, but it is clear that only some specific types of changes occur during this “adaptive mutation” (also called stationary phase mutation, or Susan’s favorite Stressful Lifestyle Associated Mutation or SLAM). It turns out that a specific type of mutation repair is turned off during starvation to allow a hypermutable state so a bacterium may escape the starvation. This repair always depends on DNA recombination (some kinds of double stranded break repairs, etc. etc.)
This has a number of implications : some antibiotics do not kill bacteria but just prevent them from growing, and depend on the immune system for cleanup. If these bacteria are basically now “stationary phase”, maybe they can become hypermutable and develop antibiotic resistance. These types of changes do occur in many types of bugs, notable Streptococcus pneumoniae which changes its penicillin binding proteins to escape penicillin.
Also, this happens in some cases in cancer cells. While not a heritable change, cancer cells which duplicate chemotherapy-resistance genes can survive better. Repeat this process 1000 times, and you get a buttload of chemotherapy genes in a cell. These form little extrachromosomal fragments called “double minutes.”
Very interesting. While this may look like a concerted effort by cancer cells or bacteria to change their genomes to survive an insult, we cannot scientifically examine a population in stationary phase (one bug in one place one day may not be the same bug in the same place the next day). So, it may just be a rapid selection and “survival of the fittest” of the random mutation of bugs or cancer cells.
I haven’t heard of this specifically in fruit flies, but I wouldn’t put it past the little buggers. I did a preliminary PubMed search and I found one seemingly relevant search in a low impact factor journal. I can’t tell much by just reading the abstract, but it seems to be a huge conclusion from data which may have other explanations.
For any system in genetics, we have to realize the Golden Rule:
phenotype (appearance) = genotype (genes) + environment.
It is often very difficult to tell what the right side of the equation is doing, especially in things like humans. With fruit flies it is a little easier, because we can mutate them and then manipulate them genetically to rapidly find a mutation. Then we can smush em and look at their DNA. Quickly.
With humans, you need pedigrees, you need tissue, you need to track down families and patients, you need consent, etc etc etc. That is why there is all of this confusion in the world - Is [trait x] genetic? This, where trait x equals learning disabilities, sexual preference, intelligence, disease, toothpaste preference, and on and on.
In terms of population genetics, with fruit flies and actually with humans, new traits can all appear or disappear rapidly. A novel mutation can go to predominate in a few generations, if the selection is strong enough. It seems to me that the events you are describing may induce a very strong selection, so the population rapidly shifts over to a new genotype.
Oops, I posted before I was finished.
When I said “no heritable change” for cancer cells, I meant not heritable for the organism, not the cancer cells. The cancer cells survive better, and keep the mutation. Kind of reminds me of the really sick article in The Onion a few weeks ago…
smack
must cut down on the vb code.
I have no problem providing an online lecture. With this type of stuff, there really is no good source. News articles tend to glamorize. The science literature, even Scientific American, is a bit difficult for the lay-person to get through. Scientists and physicians tend to get a bit heavy on the lingo, as much so I think as lawyers. It is actually really a problem – accurate dissemination of scientific knowledge is a problem faced every day in building public confidence about cloning and genetically engineered animals and foods. Most people don’t put the stuff up on the web, cause they are too busy trying to publish in the thousands of journals in the primary literature.
edwino:
I just want to say that I, for one, appreciate your efforts here. This is interesting stuff, and you are very right when you say that it’s often difficult to find this sort of thing written for the interested layman. There’s certainly a niche available out there for those folks who can disseminate jargon-free concepts to the public.
The reason that Lamarck is discredited for sexual species, is that there is no known way for changes to be passed on to the germ cells. Darwin proposed that germ cells are made up of a bunch of little components sent down by the rest of the body. Your brain might send down a little piece that described how it developed, and so on. These millions of little messengers would be passed on to the next generation. He could find no evidence for this theory, since it is wrong. (Remember, he did not know what a gene was at this time.)
Except for mutations in the individual germ cells, the genetic makeup of your offspring is determined at your conception and fetal development.
I just did more research – I read a review in the journal Cell (which is the highest impact factor journal for my field). It was about adaptive mutation in bunches of species. If you are interested, here is the citation :
Metzgar D, Wills C.“Evidence for the adaptive evolution of mutation rates.” Cell. 2000 Jun 9;101(6):581-4.
It is pretty cool. While the review focuses on adaptive evolution in bacteria, they mention a system in Drosophila which may explain this all. In most life, there is a system to ensure correct folding of proteins as they are being made. This sysem is made of “chaperone” proteins, or “heat shock proteins” (HSPs), called so because heat damages a cell by making its proteins unfold. HSPs repair this damage, in part. Anyway, these are cool little proteins that people have been knocking away on for many years, and nobody is quite sure exactly how they work.
Anyway, the fruit fly HSPs not only ensure correct folding and refolding, but they also are responsible for correct folding in mutated proteins that would ordinarily not fold correctly. That’s how mutation works – if you mutate a gene, most of the time you cause the protein it encodes to be misfolded. The chaperones generally compensate somewhat for this. In this sense, they decrease genetic variability during development, because they “mask” mutation by ensuring correct protein function.
Anyway, stick the fly in a stressful environment, and the HSPs quickly become overwhelmed by functioning cellular proteins which are becoming unfolded. The HSPs have to refold them, and the mutated proteins that they are “correcting” in the process described above are left by the wayside. They are now free to become misfolded, thus “unmasking” population variability in a stressful environment. This may explain the above references to quick genetic variability with quick reversal.
So, the interesting thing is how does a system like this (or the bacterial above) evolve? It has to evolve secondarily after it becomes linked to a favorable mutation – it is never favorable for an organism to become hypermutable, except when if it gets lucky with a favorable mutation.
edwino:
“So, the interesting thing is how does a system like this (or the bacterial above) evolve? It has to evolve secondarily after it becomes linked to a favorable mutation – it is never favorable for an organism to become hypermutable, except when if it gets lucky with a favorable mutation.”
I’m a little confused as to what is meant…the chaperone system you described is certainly an advantageous (and very cool!) adaptation for correcting protein coding errors. Are you asking how these proteins would have evolved?
As to the hypermutability, that looks like it’s simply an artifact of the way the HSPs work - there are only so many of them, and they can’t do everything in cases where things get too hectic. This isn’t an independent adaptation; if anything, it’s a break-down of a regulatory function, which leads to an explosion of variation. This gives natural selection a larger ‘pool’ from which to select - which actually sounds a lot like the SOS-effect mentioned earlier (perhaps the SOS response is the result of a similar breakdown in a regulatory process?). But, since it’s an artifact of a process, rather than a process in and of itself, it would never actually be ‘selected for.’
Mauve Dog:
It is never advantageous for an organism in a nice environment to be hypermutable. Therefore, it is only advantageous to become hypermutable if 1) you are stressed and 2) you may pick up a random advantage (to decrease the stress). So the original non-beneficial primary action (becoming hypermutable) is linked to the secondary effect (getting lucky with mutations).
It is a little more complicated than I initially described for the HSPs. HSPs are upregulated during a stress - you can stick a normal gene on an HSP promoter, and heat shock the animal and get your normal gene turned on (or induced in biolingo). The system is specifically letting some misfolded proteins escape this, however. Letting misfolded proteins escape from chaperone action is not advantageous unless there is a chance (like above) that you will get something beneficial out of it. Therefore, a secondary effect of decreasing the stress may be linked to a primary effect of letting some mutated proteins stay misfolded.
I hope this is clear. Feel free to flame, etc. if it isn’t.
There certainly doesn’t seem to be aything to flame in your post, edwino! However:
Hypermutability, as caused by heat shock, or whatever else might cause hypermutability, does not seem to be selected for. It can’t be selected for, really, because there’s nothing to act upon! As I indicated before, the hypermutability appears to be simply what happens when something that is selected for, e.g., the HSPs, fail.
It also doesn’t sound as if the HSPs are selectively allowing certain misfolded proteins to ‘escape’ - from your earlier description, they appear to prioritize the functional proteins that are starting to misfold (I could, of course, be wrong about this). Since they are limited in number, they simply don’t have the resources to deal with all of the new misfoldings as well. As a result, there are more misfoldings than would occur in a non-stressful environment. That’s not necessarily advantageous in and of itself (after all, the HSPs perform the function of limiting misfoldings under normal cicumstances), but it’s a case of “well, what can we really do about it?”
In the case of a high-stress environment, however, this turns out to be beneficial. More mutations means more ‘stuff’ for natural selection to act upon. Essentially, the probability of an adapted mutant being produced is increased. In a non-stressed environment, without the HSPs (for those organisms which have evolved them), there would probably be a very high mutation rate, but it would be completely random and non-focused. Since most mutations are negative, this would qualify as a ‘bad thing.’
I am somewhat confused by this:
“It is a little more complicated than I initially described for the HSPs. HSPs are upregulated during a stress - you can stick a normal gene on an HSP promoter, and heat shock the animal and get your normal gene turned on (or induced in biolingo).”
Not knowing much about genetic lingo (my ‘speciality’, such as it is, lies more with macro-evolutionary stuff), I’m not sure what you mean by “stick[ing] a normal gene on an HSP promoter”.
OK, so in genetics we sometimes like to turn on a gene at a precise time. One way to do this is to take the coding region of the gene and splice it onto a heat-shock promoter. (I don’t want to speak down to anyone, but I don’t know your experience, so I’ll explain this briefly).
What follows is grossly simplified. A gene in the genome contains not only the information about the code of the protein (the coding region) but also contains bits around it that dictate when and where the coding region should be produced. This is called the promoter. RNA polymerase with other factors reads promoter information to make a copy of only the coding region called the mRNA. If we isolate mRNA and make a DNA copy, that is called cDNA (complementary DNA).
Inject a construct with HSP promoter (when and where? - during a heat shock or chemical stress, expressed everywhere) linked to the gene of interest cDNA to make transgenic animals. When you heat shock the animal, you get buckets of your gene of interest produced. Crude, but effective. For example, we can take HSP-GFP (green fluorescent protein from jellyfish) flies and heat shock them. They fluoresce green after a few hours. We have better ways of inducing genes in terms of specificity and timing, but to turn on a gene everywhere at the drop of a hat, you can’t beat it.
This was meant to address your above point. I can see how I have been unclear :
An organism generally has no problem making too much of something. Proteins usually are really easy to degrade. mRNA is even easier. If it is going to upregulate something, it can make buckets of it. I can’t conceive of a situation ordinarily where too many chaperones would hurt – you would just get all your proteins folded back, and that’s it. But, due to secondary selection, in our above case, the flies at some points make too little chaperones for the situation. They are upregulated, and preferentially fold back denatured proteins, but only to the level that they cannot refold mutated proteins. This is one explanation. It just seems fairly bizarre that something can be so dynamically regulated but gets to a level just enough to refold the denatured wild-type proteins and forget about the mutant proteins.
I bet I could think up a better explanation, but that means going across the street to the library and digging for the primary literature. I’ll tell you what – I am writing a qualifier right now and if I need to go back to the library, I’d be glad to pull and read them.
RE the english moths as supposed evidence for evolution:
I seem to remember from one of my physical anthropology and/or philosophy of technology textbooks of a few years ago a piece that debunked the whole moth thing as purely anecdotal. The article was actually by an “evolutionist” (a term which also describes me, before you get your panties in a bunch) who was trying to convince the scientific education community to stop using incorrect and inaccurate metaphors, as they actually give the creationists more ammuntion. There was a whole list of scientific sacred cows… damn, I wish I had a cite.
Well, there were some problems with the peppered moth thing as originally published, but it’s not purely anecdotal. The Peppered Moth - An Update. I believe the only real controversy left is over the significance of the findings, with the creationists saying that it’s only microevolution or that it’s even less significant than that.
edwino wrote:
It seems to me that if there were too many chaperones, variation would actually be decreased, since, in times of non-stress, most of the mutant proteins would be getting re-folded. That, and if their aren’t too many misfoldings, you get a lot of these chaperones being idle.
In times of high-stress, if there is an abundance of chaperones, then the functional proteins would be able to get re-folded, and there would still be several left over to catch the mutants. Again, variation would be decreased, perhaps to the detriment of the population. So, perhaps the current levels (just enough to keep the functional ones repaired during high-stress times, but not so many as to lessen any chance of a beneficial mutant) have been evolved for just that purpose.
Mauve Dog:
The only issue I have with this is that it is almost always beneficial for an individual to suppress “variety” in a population – the variety is caused by mutation, which is almost always detrimental. Increasing variety by increasing the level at which mutation is expressed will almost always cause a population to be less viable, as many more individuals are now inviable.
I certainly agree that most mutations are detrimental. However, variety is the ‘stuff’ that natural selection selects from. The case of flies is not any different than what would normally happen in a population; it is simply accelerated by the overworking of the HSPs. In any given population, there will be some degree of variation from one generation to the next. Via natural selection, the most detrimental forms are weeded out and the most beneficial ones remain. When HSPs go bad (so to speak), the amount of this variation increases. Most of these, of course, should be ‘bad’ mutations, but perhaps the system remains in place because overall the odds of a ‘good’ mutation surfacing are improved. Or, at the very least, the number of individuals with a beneficial mutation is increased.
Actually wait… now that I think back a whole 3 months ago to my Bio class. Didn’t Lamarck believe that animals “willed” themselves to adapt? For example, giraffes used to have short necks. They realized that up high was where the food was, and told themselves to grow longer necks. I totally forgot that fact. Thats why I think he was an idiot.