theyeti

Sorry David. Truth is I haven't been around much. But I will go through your last reply.

A duplication or other addition of DNA does come at a cost. For the most part, the cost is very small, so that if the extra DNA helps out in even a slight fashion, then the benefits will outweigh the costs. If the addition means the addition of an antibiotic gene, then it will be preserved if the bacterial population occasionally runs afoul of antibiotics. Do also keep in mind that for most other organisms -- those that don't replicate every 20 minutes -- extra DNA is insignificant metabolically speaking.

Any time someone starts talking "information", my eyes start to roll. You will have to be very specific in what you mean by information, what you mean by complexity, and how the two relate to each other. You are right though in that the most common way to increase "information", taking it in the intuitive sense, it through gene duplication. Sometime through duplication of the entire chromosome.

Who says the odds are massive (and I assume you meant massively small)? Gene duplications, or lateral transfere, adds immediately functional genes to the genome. This is different than the addition of a random sequence, or the randomization of an already existing sequence. Now the function may be redundant or unnecessary, in which case we expect the bacteria to lose the extra gene. But if it's useful somehow, then the bacteria should keep it.

You're getting a bit confused. Neutral, by defintion, means that it won't cause any harm. If it is slightly disadvantageous, by putting an increased metabolic load or something, then it is weakly harmful, if it doesn't provide a benefit of some kind. In the cases where antibiotic genes get added, there is clearly a benefit of some kind if antibiotic are occasionally present, and so therefore the gene cannot be thought of as harmful. But it does come at a cost. This is why if the bacteria never run across antibiotics, then the extra gene can be thought of as weakly harmful, and thus natural selection should remove it. Remeber when I talked about beneficial/harful being defined by the environment? This is what I was getting at.

Huh? The addition of DNA is bad if the DNA doesn't have any benefit. Like I said before, plasmids are best thought of as symbionts who are looking out for their own interests. Those interests don't always coincide with that of their host. R plasimids (those that carry antibiotic resistance) are giving a benefit to their host, and are thus more likely to survive themselves. F plasimids, the ones that cause conjugation, are probably not helping their hosts much, and possibly hurting them. But though conjugation they manage to make copies of themselves, which means that they will continue to persist, even if their host has its fitness lowered.

You've brought up a number of reasons yourself. Mutations are random, and they have to occur at a low enough frequency to prevent genomes from becoming randomized, otherwise the species is dead. Your whole argument here has been that the odds of a benefical mutation occuring are very slim. That argument has its problems, but the chances of certain mutations are slim, and thus they only occur every thousand/ten thousand/million years or so. Also, like I've been saying, the chances of a beneficial mutation depend on the environment. Organisms that are well adapted to their environments don't recieve many beneficial mutations, and thus don't evolve very much. It requires a change in environment, sometimes on a global scale, to induce "rapid" evolution. (Rapid in this case means many thousands or a few millions of years).

There are lots of different things that can cause antibiotic resistance. Often they include changes in enzymes so that they can digest the antibiotic. Sometimes it's changes in transport proteins such that they either don't import the antibiotic, or they are good at exporting it. Sometimes it's changes in the target of the antibiotic such that the antibiotic will no longer bind. There are all sorts of things, and I have to admit that I'm not too well studied on the subject. Some of them, in the absence of the antibiotic, will cause the bacteria to be less fit. In this regard, it's no different than the addition of a plasmid.

The ones that take in a plasmid.

I don't know when I'll be able to reply to you again, David. We seem to be going around in circles anyway, so TTFN.

theyeti

[ March 24, 2002: Message edited by: theyeti ]</p>

davidH

Yeah, don't worry if you can't reply for a while. I'll still be around.

Though we sometimes seem to be going around in circles I think we are progressing along! lol. I've learnt a lot of stuff I didn't know before so you have been a help - thanks.

I've just got a few more questions to ask though - since it is such a massive topic.

But at the minute I'm waiting for some info from Morpho, I can't reply now but I will soon.

davidH

Yeah, but we are talking about a mutation that is neutral here - so if the extra DNA helps out in no way at all then that extra DNA could potentially destroy that bacterium - cause there will be no benefit to outway the cost.
(Since the mutation is neutral I am assuming that it is neutral incontext with the environment the bacterium is in).

True that many organisms wouldn't replicate every 20 minutes - but bacteria are some of the "simplest" creatures so I am assuming that they come at the bottom or very low in the evolutionary tree.

lol, yeah. Well, what I mean is new and previously unhad abilities resulting from new mutations.

So if the most common way to increase "information" is through gene duplication and sometimes duplication of the intire chromosome then these duplications must never be neutral - since if they are they will put the bacterium to a great disadvantage - potentially causing it to be outcompeted.
But if there is a benefically mutation in there that will cause it to outcompete it's fellow bacterium then it will excell.

Yeah, but if it won't cause any harm to the bacterium it has to be a benefically mutation and not a harmful one.
So in that sense there is no such thing as a neutral mutation - it will either be benefical or harmful.

If it is "neutral" it will increase the metabolic load and so be classed as harmful and that gene will be lost as the bacterium is outcompeted. If it is physicallyy harmful again it will outcompeted.

However if it is benefical then it will be retained as the bacteria competes more sucessfully against its fellow bacteria.

Yes, exactly - it is a benefit because of the environment that the bacteria are in. But as soon as that same bacteria is taken away from the antibiotic environment it is out competed and removed by natural selection since that same gene now becomes harmful - it doesn't become neutral.

So can evolution then be observed - if the scientists put organisms in controlled environments and then increase the mutation rate so that it occures far more often?

Yeah, I had been wondering about this. I wonder if you would be able to explain it to me.
Those bacterium that take in a plasmid - say that plasmid contains the information for an emzyme that can digest that antibiotic. Surely the code for that enzyme would occupy the same gene loci as the code for another enzyme in the bacteria.
- The same gene loci where the mutations on one enzyme turned it into another enzyme that happened to digest the antibiotic.
Well, how exactly does the bacteria take up the new information.

eg. Does it stop making the enzyme that it had been making and start making the enzyme that the plasmid codes for.
Or does it make both of them - just starts making the new enzyme and carries on making the old one?

Well I have to head on here again.
Hope you can reply.

theyeti

I'm going to try to do this quickly before my supervisor catches me...

David, you're a bright guy, and I don't know why I'm not getting through to you on this. A "mutation" (using the term in the broad sense) cannot be simultaneously neutral and harmful. It is either one or the other. If there is a substantial cost, and no apparent benefit, then it's harmful. If there is no substantial cost and no apparent benefit, as most duplicates will be with most organisms, then it's neutral. In bacteria, superfluous DNA is generally weakly harmful (but it won't "destroy" the bacterium for Christ's sake). But, if it provides a benefit, even only occasionally, then the costs will likely be outweighed, and the extra DNA will be retained.

Okay assumption I suppose. Do keep in mind that bacteria were around for 1 billion years or more before the first single celled eukaryotes appeared. Therefore, there probably was a difficult evolutionary path up to greater "complexity".

Right, but duplication is one of the main ways that this can occur. The duplicate gene, if it's not needed for the same function, can diverge into a new or related function. It can also be regualted differently than it's twin so as to increase an organism's complexity.

Here is one of the better reviews on the subject:
<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=116823 12&dopt=Abstract" target="_blank">Curr Opin Genet Dev 2001 Dec;11(6):673-80</a>, Evolution of novel genes.

Here are a few brand new papers that I hadn't seen before:

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=118841 42&dopt=Abstract" target="_blank">J Mol Biol 2002 Mar 8;316(5):1041-50</a>, Gene duplication and gene conversion shape the evolution of archaeal chaperonins.

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=118618 87&dopt=Abstract" target="_blank">Mol Biol Evol 2002 Mar;19(3):278-88</a>, Reconstructing the duplication history of tandemly repeated genes.

Cool stuff! But not as cool as this:

<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=119043 80&dopt=Abstract" target="_blank">Proc Natl Acad Sci U S A 2002 Mar 19</a>, Origin of sphinx, a young chimeric RNA gene in Drosophila melanogaster.

Goodbye, specified complexity.

You've mostly got this right. However, it is rarely a "great" disadvantage. It's almost always a tiny disadvantage, unless there is a huge duplication. There is plenty of time for mutation to occur before the duplicate will get weeded out of the population. Also, new duplicates are constantly arising, so even though many are getting weeded out, they are always being replaced. In eukaryotes, this occurs through unequal crossing over, but I'm not sure about prokaryotes (maybe pseudobug or Queen of Swords could answer this). I assume duplication occurs through some kind of lateral transfere, usually between the main chromosome and a plasimd I would think. Presumably, a particular gene duplication would remain at low frequency until it was advantageous, at which point in time it would increase in frequency until it became fixed.

In a sense, yes. But remember, we are only talking about duplication here. Most point mutations can be thought of as truly neutral in that they have no effect on enzyme activity or whatever it is that the protein does. Generally speaking, it's hard to conceive of a truly neutral mutation, just as it's hard to conceive of a truly commensalisitic symbiotic relationship (where the host is neither helped nor harmed). Afterall, there is usually some way in which there will be an impact, no matter how tiny. However, for practical purposes, a "mutation" can be considered neutral if its benefit or harm is not enough to overcome the effects of random drift. This includes most duplications in larger organisms like human beings, and certainly a large percentage of point mutations in all organisms.

Yes, I think you're getting it. Just remember that mutational pressure will cause many "harmful" alleles to remain at low frequency, including superfluous duplicates.

I don't know if you're trying to make a point here though.

Right. But it will generally be removed very slowly, since it is only weakly harmful. (In fact, it may never be removed completely due to mutational pressure, but surely all forms of antibiotic resistance won't be maintained in a finite population) In the presence of antibiotic, the resistance gene is strongly beneficial, and will become fixed almost immediately. Therefore, there needs to be only an occasional dose of antibiotics to retain the gene.

Nevertheless, if we quit using antibiotics permanently, almost all antibiotic resistant genes would sooner or later go extinct. It would cost us many millions of lives, but what the hay. Of course, as soon as we started using them again, bacteria would again start evolving resistance.

BTW, you may be interested in this recent article: <a href="http://www.iscid.org/ubbcgi/ultimatebb.cgi?ubb=get_topic;f=1;t=000028" target="_blank">Darwin's Time Machine: Scientists begin predicting evolution's next step.</a> The article is about predicting how bacteria will evolve resistance to new antibiotics. Ironically, it's posted at ISCID, the ID "academic" society started by Dembski.

Absolutely. This is done all the time, and there is all sorts of literature about laboratory evolution of bacteria (though don't expect to see any cited on your creationist web sites; try PubMed instead )However, increasing the mutation rate is not always a good idea, since this can change the parameters of the selection process (in other words, good mutations can be swamped out by bad ones if the mutation rate is too high; in fact, you may end up selecting for resistance to the mutagen!) But increasing selection pressure is one good way to accelerate evolution in the lab.

The second one is right. The plasmid is not connected to the main chromosome, and so therefore any genes it carries are in addition to the ones that the bacterium already has. It is truly new "information" in any meaningful sense of the term.

In other cases, an enzyme already present can be altered to to digest the antibiotic. Usually, this will lower its ability to perform its other function, and is thus harmful in the absence of antibiotics. However, if that gene duplicates, then one copy can do the original function while the other specializes in digesting the antibiotic. This is roughly the "subfunctionalization" model of gene duplication, and is thought to be a major force in the evolution of new genes.

Well, that wasn't quick at all. I will probably be able to reply to sometime over the weekend, but not much after that.

theyeti

&lt;edited to fix url&gt;

[ March 29, 2002: Message edited by: theyeti ]</p>

davidH

Right, I need to get this cleared up.

When you talk about evolution and mention the word mutation - what sort of mutation are you mostly referring to? Are you referring to those that are caused by radioactive sources? Or those that arise during mitosis, meiosis etc?
Like those that are used in Laboratory experiments - what do they use to induce the mutations?

Also - from the quote above why couldn't the DNA sequences that allow the bacteria to hydrolyze cefepime already exist in nature? All it needs is this bacteria to come into contact with this drug and it has a competitive free environment.

You see from what I have learnt here - the antibiotic resistance bacteria are actually no big problem that it is made out to be.
Surely a simple but effective cure would be to stop trying to make more and more powerful antibiotics that the bacteria are resistant to, but to put those bacteria in competition with other less dangerous bacteria.

Once this has been done, the antibiotic resistant bacteria will be out competed by the other bacteria and basically their levels will drop.
Then a dose of antibiotic can be given to drop the levels of the less dangerous bacteria to a level that the body can cope with.
Thus both bacteria are at levels that the body can now control.

Surely that is better than providing an environment that a certain bacterium can colonise for lack of competition and so cause the patient to be worse off than when they came in.

True that what I have described is probably over simplified - but from what has been said here shouldn't that work?

The other point about the neutral mutations in bacteria. The only thing I was trying to work out was how you could say that the majority of mutations could be neutral, and some harmful and some benfical.
Because from what I have already put up I have seen that the "neutral" catagory of mutations would actually still have to come under the harmful catagory.
That was all - I was just trying to work out how you could say that the majority aren't harmful but neutral when actually the neutral mutations are essentially harmful to the bacteria.

But maybe you were referring to larger more complex organisms when you said that.

Thanks for the info about the plasmid - that was interesting to see how a bacterium can do all that.

Yeah, I'll have a look there.
One thing I am curious about - when u are talking about the laboratory evolution of bacteria - are they still essentially bacteria once they have evolved but just more specialised. Or are they actually completely different from the bacteria.
ie. Is "macroevolution" observed or is there only a certain point that the bacteria can evolve to?

Thanks also for the links - some interesting and new things for me there.

theyeti

I don't know that it really matters. In the laboratory, I think they use chemical mutagens and sometimes UV radiation. They can also use certain bacterial strains that have error prone polymerases and such and thus have an intrinsically high mutation rate. But many evolution experiments don't induce mutations at all, they just rely on the normal background rate. Like I said before, it is usually the selection pressure that the researchers manipulate to better model what goes on in nature.

In nature, all of those things that you mention cause mutations. Copying errors during mitosis (or fission in bacteria) are one way. Unequal crossing-over during mieosis or other kinds of recombination are another way (these can often cause duplications, "shuffling", etc.). Various kinds of chemical muatagens, including occasional cellular byproducts, cause mutation too. And of course radiation, often UV but also higher frequencies, are a main cause of mutation. In fact, no matter how much you sheild an organism from mutagens, it will still have a low "background" rate of mutation like I mentioned before. This is largely because the DNA polymerases and other reproductive mechanisms are imperfect; quite remarkably good, but still imperfect. There are also other mechanisms that do "proof-reading" and such to lower the number of errors. However, when the bacterium is stressed, these mechanisms often don't work as well and the mutation rate increases. In the laboratory, researchers can use error prone polymerases or proof-reading deficient bacteria to increase mutation rates. They can also put the organisms under stress and see what happens then. Sorry I can't be of more help here, but I'm just not that familiar with this sort of thing. All in all though, what you ask is a factual question that can be answered with sufficient reseach (again, go for PubMed; avoid AiG).

In a sense, the muations do exist in nature before the bacteria come into contact with the antibiotic. Remember, muations occur constantly, and therefore there is always variation within the population. The mutations that hydrolyze cefepime probably arise occasionally, but because they are neutral or harmful, they either get weeded out or do not increase to a significant proportion. When cefepime gets used more liberally, then those mutations become strongly beneficial, and that particular genotype will increase to high frequency. Evolution in a nut shell.

That's pretty sound reasoning. This is exactly why it's important for students, especially those in the medical community, to study and understand evolution. Your scenario is pretty accurate in most cases. The bacteria that live in out gut are helpful to us because they out-compete potentially harmful bacteria that would live there otherwise. However, there are many tissues and organs, like the brain, that must remain germ free. When those get infected, even with normally innocuous bacteria, antibiotics are the only way to get rid of them. So we're not going to be able to do without them anytime soon. We'll just need to find a way to cope with antibiotic resistance, and studying evolution is probably the best way to do that. I myself make no claim to understand the dynamics in such a way as to make the best recomendation, but it's important not to overpercribe antibiotics so as to limit the benefits of being antibiotic resistant.

Well, I hope that's cleared up now. "Neutral" is a relative term. It's best to think of a threshold of harm or benefit below which a mutation should be considered neutral due to it's extremely weak effects. The superfluous DNA bit (like with uncessary duplications) is really a different issue than point mutation, and it's only weakly harmful in fast reproducers that spend a lot of metabolic energy on DNA replication and maintainance.

That depends on how you define "macroevolution". In nature, the evolution of simple single-celled eukaryotes from bacteria took a billion years or more, and is unlikely ever to happen again. If that's what you're expecting, then no, it hasn't been observed and probably never will be, nor should it be.

However, bacteria in laboratory evolution experiments have evolved quite a lot of morphological change. The sort of change that would be equivalent to reptiles evolving into birds, and thus would be considered "macroevolution" by most defintions. One article you should read is Science 284, June 15, 1999 p. 2108-10, "Test Tube Evolution Cathes Time in a Bottle". Here are a couple of choice quotes:
...
Here's another paper: <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=100971 19&dopt=Abstract" target="_blank">Proc Natl Acad Sci U S A 1999 Mar 30;96(7):3807-12</a>, Genomic evolution during a 10,000-generation experiment with bacteria.
Here is a <a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Display&dopt=pubmed_pubme d&from_uid=10097119" target="_blank">PubMed</a> search using the "related articles" button on that last paper. You should browse the abstracts of these articles to get an idea of what goes on in laboratory evolution.

What irritates me about the "macroevolution" demand is that it's a case of moving the goal posts without acknowleding what's being conceded. Cases with bacterial evolution in the lab and other cases of short-trem evolution out in nature are indicative of an ongoing process; if extrapolated over time, this process accounts for the incredible diversity of all of living things. Creationists often claim that evolution can't create "novelty" or "new information" or that it can't be observed. These examples clearly refute all of that. Then the creationist simply shifts the goal posts by demanding to see extreme morphological change in a relatively tiny span of time, something which is neither necessary to account for life's histroy nor is predicted by evolution.

This is usually accompanied by a semantic shell game where the creationist says, "so what if we observed that evolution, either way the organism is still a (insert taxon here)". One can play that game ad infinitum, because one can always appeal to a higher taxonimc category to claim that sufficient change is not taking place. So what if birds evolved from dinosaurs, they're still vertebrates. Your theory of evolution is a stupid fairy tale unless you can show me something impressive.

Futhermore, this claim betrays an ignorance of how evolution works; species diverge from common ancestors and thus always retain some ancestral characteristics. The point at which they are considered something "different" is completely arbitrary and not really a useful concept at all. The creationist instance of something "different" is a case of them projecting their useless "kinds" categorization onto evolution, where is simply doesn't fit.

The whole point of lab evolution and other forms of short-term evolution is this: what we see going on is adaptive change, and that is the essence of evolution. Exactly how and why larger scale transformations occured over extremely long periods of time are an interesting issue, but they are irrelevant to the illustration of the process, which is at work right before our very eyes.

theyeti

[ March 30, 2002: Message edited by: theyeti ]</p>

davidH

Thanks theyeti for that reply - sorry I haven't replied in ages again! I'm, trying to get my act together here!!

Yeah, I looked up those articles you gave - they are pretty interesting. So no evolution from bacteria to something else can be seen basically because it takes so long to achieve that kind of level.

Yeah and I disagree with that quote you gave that the creationist said there.
That fellow is wrong for the reasons you gave - it seems he is clutching at straws there - that's like saying that all mammals are the same cause they are all mammals. But anyway..

Yo, I have to go here. I will be back soon!!!

Yo you know if Morpho is still around - he said he would get me some information but maybe he forgot. I dunno.

Quetzal

Damn, davidH - I did send the request down, but forgot to follow up. I'll get back to you. Sorry.