How do you recognise a beneficial mutation?

Thank you kindly Coragyps...on my way to the Nature website to get a copy.Cheers,
M

Linking any particular condition to a segment of the
genome is, I can imagine, a matter of extremely hard work.Relating certain diseases to family lines has been done
since before genetics was fully understood.This was the sense in which I meant my questions here.Heamophilia, for example, has been known to be passed on in
families (in modern terms it represents a detrimental mutation)
and is identified through its expression. Finding the gene
that causes it may be hard, but identifying its existence
is not.Beneficial mutations, since they will not cause a 'disease' as such
will go unnoticed at this level, and go unnoticed unless someone
is studying the part of the genome where the mutation is evident.Unless we sequence every individual within a population (or sample
the population every so many generations) it is unlikely that
we will be able to spot such non-detrimental mutations as readily
as those which are expressed in a form we would consider 'disease'.

Hi Peter,
I see what you mean now. However, sometimes if a particular disease is very common in a particular group (that is not highly inbred) it can be a sign of a beneficial mutation that confers its benefits on a heterozygote i.e. sickle cell, or cystic fibrosis. Of course, it is all relative to the environment...todays detrimental mutation could be tomorrows beneficial mutation. But all in all you are correct that it is usually easier to identify things when they go wrong.Cheers,
M

My main reason for bringing this up is to suggest that
arguments based upon the 'there are no beneficial mutations'
are unsubstantiated.I hadn't considered things like sickle cell though ... although
I guess the benefit might not have been reaslised if the
'disease' wasn't there too.

Hi Peter, Sickle cell is a fascinating example of how stabilizing selection works to maintain the frequency of a mildly deleterious mutation in a population. People that are homozygous for the trait are at significant risk of dying before reaching reproductive age through acute anemia. People who are homozygous for the absence of the mutation, living in an environment where the Falciparum parasite is endemic, are at significant risk of dying from malaria. People who are heterozygous AND living in a malaria infested area are only mildly anemic and greatly protected against malaria. A genuine evolutionary tradeoff. The frequency is kept more or less in equilibrium because 50% of possible combinations are deleterious.In the absence of malaria (hypothetically), the mutation would probably be more deleterious, and even a mild anemia might cause directional selection to weed it out.

It seems to me any mutation or allele that is observed to increase in frequency over and above what could be expected by drift or other stochastic factors could be suspected of being under positive selection, ie. 'beneficial', or at least closely linked to another that is.Of course, further work would be needed to confirm that suspicion.KC------------------
Those who know the truth are not equal to those who love it-- Confucius

KCdgw - That exact point was mentioned in the Modiano article I cited up thread. They hypothesized that, were it not for modern medicine keeping malaria at bay, the hemoglobin C mutation would continue to spread through West Africa. It's already pretty widespread in Burkina Faso, but the selective pressure to maintain it is not as strong as a century ago - there are drugs to keep kids from dying of malaria now.

Dear Schraf,You say:I would like to mention two things:1) I have a mutation which could have been detrimental or beneficial depending upon what my environmant was; missing wisdom teeth.PB: Let's have a look at this. The son of my former hairdresser didn't have wisdom teeth either. I do miss two of them. I think we three must be closely related. Or could it be that the 'mutation' is introduced non randomly, preexisting in the human MPG?
This is exactly what Darwin observed too in his pigeon breeding experiments. The MPG in action. Don't confuse it with the big word: evolution. It is an unwarranted extrapolation.2) Why are there no Creationists in this thread?PB: When this thread was started I was suspended for seven days. But I am back. Interesting thread, though. I will check it out in more detail.Best wishes,
Peter

Dear Mammuthus,Concerning your first example:Proc Natl Acad Sci U S A 2003 Feb 4;100(3):1072-7 Related Articles, LinksParallel changes in gene expression after 20,000 generations of evolution in Escherichiacoli.Cooper TF, Rozen DE, Lenski RE.Center for Microbial Ecology, Michigan State University, East Lansing, MI 48824, USA. cooperti@msu.eduTwelve populations of Escherichia coli, derived from a common ancestor, evolved in a glucose-limited medium for 20,000 generations. Here we use DNA expression arrays to examine whether gene-expression profiles in two populations evolved in parallel, which would indicate adaptation, and to gain insight into the mechanisms underlying their adaptation. We compared the expression profile of the ancestor to that of clones sampled from both populations after 20,000 generations. The expression of 59 genes had changed significantly in both populations.PB: Sound familiar: EXPRESSION of PREEXISTING genes. Hay, change is at the level of gene expression. Why am I not surprised? Get real evo's, nothing 'evolved' here. All we have is differential gene expression that is selected for.(cont): Remarkably, all 59 were changed in the same direction relative to the ancestor.PB: Hay that sound a lot like non random change.(cont): Many of these genes were members of the cAMP-cAMP receptor protein (CRP) and guanosine tetraphosphate (ppGpp) regulons.PB: That sound alot like NRM in DNA elemnts that regulate gene expression.(cont): Sequencing of several genes controlling the effectors of these regulons found a nonsynonymous mutation in spoT in one population.PB: I am interested in the mutations in the other eleven population. Why not show them?(cont): Moving this mutation into the ancestral background showed that it increased fitness and produced many of the expression changes manifest after 20,000 generations. The same mutation had no effect on fitness when introduced into the other evolved population, indicating that a mutation of similar effect was present already.PB: talking about non randomness.(cont) Our study demonstrates the utility of expression arrays for addressing evolutionary issues including the quantitative measurement of parallel evolution in independent lineages and the identification of beneficial mutations.PB: and these studies demonstrate that change is non random.Best wishes,
Peter

You might try reading the paper rather than mining quotes out of context from the abstract Peter.Oh here is a beauty of a quotePB: Get real evo's, nothing 'evolved' here. All we have is differential gene expression that is selected for.M..oh my, selection for mutations that cause beneficial changes in gene expression..and there is not evolution going on here?...I guess if I say the sky is blue you will also say no PB: PB: That sound alot like NRM in DNA elemnts that regulate gene expression.M: That sounds like an assertion without support...demonstrate that what you are saying has merit rather than re-iterating nonesense.PB: (cont): Moving this mutation into the ancestral background showed that it increased fitness and produced many of the expression changes manifest after 20,000 generations. The same mutation had no effect on fitness when introduced into the other evolved population, indicating that a mutation of similar effect was present already.PB: talking about non randomness.M: Talk about not being able to read Peter...the researchers INTRODUCED the mutation themselves to see if it conferred it conferred an advantage on the ANCESTRAL population...how you think this has anything to do with testing randomness of mutations puts your scientific credential even further in doubt.PB: PB: and these studies demonstrate that change is non random.M: the only thing non random is that if someone says cheese you say non-random...open your eyes.

quote:

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1) I have a mutation which could have been detrimental or beneficial depending upon what my environmant was; missing wisdom teeth.

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PB: Let's have a look at this. The son of my former hairdresser didn't have wisdom teeth either. I
do miss two of them. I think we three must be closely related. Or could it be that the 'mutation' is
introduced non randomly, preexisting in the human MPG?
This is exactly what Darwin observed too in his pigeon breeding experiments. The MPG in action.
Don't confuse it with the big word: evolution. It is an unwarranted extrapolation.

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A number of points spring to mind:i) Whether based upon an MPG or simply evidence of genetic diversity
the visible result is that some people get wisdom teeth some don't.
There is no indication in this example that an MPG is required.ii) Evolution is defined as a change in allele frequency within
a population over time. So evolution is the correct scientific
term to use when we can see such a change (even if we do not agree
on the mechanism).iii) In evolutionary terms you are closely related to both your hair-
dresser and her son iv) You do not need to have suffered the mutation personally to
exhibit the trait. With co-dominant traits they can exist quite happily in the genome for generations ... and if there is no
selective pressure then ... well ... natural selection will not
cause a bias toward any one particular expression.

Hi Peter,You say:A number of points spring to mind:i) Whether based upon an MPG or simply evidence of genetic diversity
the visible result is that some people get wisdom teeth some don't.
There is no indication in this example that an MPG is required.PB: it clearly indicates that these info is already present in the genome.ii) Evolution is defined as a change in allele frequency within
a population over time. So evolution is the correct scientific
term to use when we can see such a change (even if we do not agree
on the mechanism).PB: Let's make this clear for once and for all:Evolutionist define it like this since now they are able to compare two unequal phenomena (apples and oranges). However, what evo's take as the definition for evolutionism is simply the definition of population genetics, and has NOTHING in common with evolution from microbe to man. Polpulation genetics is the biological disciplin that studies the change in allele frequency within a population over time.
Get your definitions right.iii) In evolutionary terms you are closely related to both your hair-
dresser and her sonPB: It is known for 2000 years that we are all brothers and sisters (connected through the MPG).iv) You do not need to have suffered the mutation personally to
exhibit the trait.PB: Exactly. That's what it is all about. It is non-Mendelian genetics and it demonsstrates that traits can be activated independent of each other. Mediated by DNA elemenst preexisting in the genome, and probably activated through recombination. This is what Darwin observed, and all evo-biologists study and confuse with the big word: evolutionism from microbe-to-man.PB: With co-dominant traits they can exist quite happily in the genome for generations ... and if there is no
selective pressure then ... well ... natural selection will not
cause a bias toward any one particular expression.PB: And all elemenst to repress and activate these traits are already present in the genome. Or did they drop out of the sky somewhere?I more and more get the conviction that evolutionists don't understand their own theory.Best wishes,
Peter

Dear Mamuthus,M says: Talk about not being able to read Peter...the researchers INTRODUCED the mutation themselves to see if it conferred it conferred an advantage on the ANCESTRAL population...how you think this has anything to do with testing randomness of mutations puts your scientific credential even further in doubt.PB says: The researchers also demonstrate that the mutation does not further compensate in micro organism that have also adapted phenotypes, INDICATING that the all have the same/similar mutations. Randomness? You claim it, I doubt it.have a good one,Peter

PB says: The researchers also demonstrate that the mutation does not further compensate in micro organism that have also adapted phenotypes, INDICATING that the all have the same/similar mutations. Randomness? You claim it, I doubt it.M: LOL!!!
Of course they have similar mutatant phenotypes...read the freaking paper. They did a positive and negative control (you do know these concepts don't you????) They moved it onto the ancestral background and saw the increase in fitness. Then they moved it into various mutants that had ALREADY been selected and saw no increase in fitness because they were already adapted...due to similar (you claim now that similar mutations are non random? So any mutation that occurs anywhere was non-random ) mutations in the metabolic pathway. So it they moved a specific mutation onto a background that was generated by random mutation. You really need to start paying attention...and take a freakin statistics course...maybe some basic biology while you are at it.

Also for your information:"If under a particular environmental stress a wobbly enzyme is induce with the purpose to spawn billions of slightly different clones, than that is a preexistinmg mechanism to ensure the organism isn't wiped out immediately. Such a mechanism hasn't even to be perfect or deterministic --quasi deterministic would be sufficient. That is what we observe in the genome of microorganism. Rosenberg did some nice studies on it demonstrating that the mutaions are not pure random. (see 'cairns excerpt' posted by Dr Page, about 8 months ago)"In Germany it should be around 9.30 am. Nothing to do in the lab? Maybe you could do some nice experiments to exclude NRM Anyway, seeya mate.[This message has been edited by peter borger, 04-01-2003]