How do you recognise a beneficial mutation?

It is often stated by anti-evolutionists (if you'll forgive the
label) that mutations are, by-and-large, detrimental.I would like to ask how one would be expected to recognise
a beneficial mutation.We recognise detrimental mutations due to their limiting effect
on the organism in question.In the main, it is the absence of some function that makes us
realise that it was necessary in the first place.If we add a new function, or add something that improves an existing
function ... how would you know?The organism would live a fruitful existence without presenting
any noticeable difference from its peers ... unless external
factors change in such a way that the change becomes recommended
or essential.

Here are few references on this topicfor example in bacteriaProc 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. Remarkably, all 59 were changed in the same direction relative to the ancestor. Many of these genes were members of the cAMP-cAMP receptor protein (CRP) and guanosine tetraphosphate (ppGpp) regulons. Sequencing of several genes controlling the effectors of these regulons found a nonsynonymous mutation in spoT in one population. 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. 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.in humansPayseur BA, Nachman MW. Related Articles, Links
Natural selection at linked sites in humans.
Gene. 2002 Oct 30;300(1-2):31-42.bacteria againShaver AC, Dombrowski PG, Sweeney JY, Treis T, Zappala RM, Sniegowski PD. Related Articles, Links
Fitness evolution and the rise of mutator alleles in experimental Escherichia coli populations.
Genetics. 2002 Oct;162(2):557-66.and fruit fliesHarr B, Kauer M, Schlotterer C. Related Articles, Links
Hitchhiking mapping: a population-based fine-mapping strategy for adaptive mutations in Drosophilamelanogaster.
Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):12949-54.
PMID: 12351680 [PubMed - indexed for MEDLINE]

So to find beneficial mutations seems to require deliberate
research effort, coupled with a healthy amount of genomic
data analysis.Finding a detrimental mutation can be as easy as looking at
the organims, or other clinical signs.How then can one say 'there are far more detrimental mutations' or
there are 'no beneficial mutations' in a discussion on evolution.The above papers would tend to confirm that there ARE beneficial
mutations. The research effort required to find them would suggest
that they are hard to spot unless you are looking for them.

Hi Mammuthus,I appreciate (firsthand) the effort it takes to dig out references, but though I'm a pretty resourceful guy () I wasn't able to access all of the references online.The Proceedings of the National Academy of Sciences requires a $125/year subscription.Gene (404) didn't give an online subscription price, I suspect you have to subscribe to the hardcopy version to gain online access.The Genetics article is available online: Could you provide some discussion for the unavailable references? I know it seems unfair to ask for extra homework from someone who's already done his homework, but hey, no good deed goes unpunished! ------------------
--EvC Forum Administrator

No problem...but it will have to wait until tomorrow...I am used to being spoiled by having access to most of the materials

Hi Peter
Just a quick answer to this..it takes a truckload of research to identify detrimental mutations as well. Alzheimer's for example is not particularly easy to dissect genetically..and it is still a work very much in progress. When you look at slightly deleterious mutations it becomes even more difficult. So I would not necessarily say it is easy to find detrimental mutations and hard to find beneficial mutations...to complicate matters, being a heterozygote for extremely detrimental mutations can confer an advantage with the cost being that you end up with a lot of people suffering from specific genetic diseases because of the higher chance of inheriting two mutated alleles.cheers,
M

My favorite "beneficial mutation" is the one that codes for hemoglobin C in humans. It's pretty common in West Africa - homozygotes have 7% of the incidence of clinical malaria as homozygotes for boring old hemoglobin A. Unlike sickle cell, most people with HbC never know that they have it - a few have spleen problems. My references on this are at home, but I'll put them here tonight if anyone's interested.

I think one of the things people misunderstand about mutations is that the vast majority of them are neither beneficial nor harmful. "Mutants aren't monsters" is the saying. Simply put, every organism has a bunch of mutations. Mutations come from exposure to radiation (like UV or gamma rays) or certain chemicals (mutagens). In the vast, vast majority of cases, the mutation is to a gene that doesn't appear to do anything. In fact all that junk DNA might be a mechanism to protect the "real" genes. Other times, the mutation changes an operating gene but, through redundancy, it codes for the same protien.The point is that we all acquire mutations. You have millions. I have millions. The vast majority prove to have no effect on an organism's survival. Whether it's a beneficial mutation or not is more related to the environment than to the particular gene. If the mutation doesn't change fitness, then it's very likely passed onto the next generation. Scientists have identified many of these harmless mutations in our own DNA, passed on from generation to generation in some populations because they don't affect fitness.Some genes are both harmful and helpful, like the sickle-cell anemia gene. One copy of it improves your resistance to blood-bourne parasites. Two copies gives you fatal anemia. One copy of the gene is sufficiently helpful in Africa that in regions of high exposure to malaria, most people have at least one copy of the gene. In those regions, the occurance of sickle-cell anemia is high, but it's not enough to outweigh the survival advantage of one copy of the gene.It's all in the environment, really. Whether or not a mutation is beneficial is just circumstance, an accident of context.

I wanted to repost this simply because this is such a succinct and accurate statement of "beneficial" vs "deleterious" mutations: Without relation to the environment, discussing whether a change in genome is beneficial or not is meaningless. Saying something like DDT resistance is "beneficial" is useless if the organism lives in a environment devoid of DDT.Welcome to the forum, crashfrog!

Hi Coragyps,
Yes, please post the reference. I really like those types of studies. They go a long way to explaining the high frequency of specific diseases like cystic fibrosis in populations of european descent. There are several diseases that occur at very high frequency and a large fraction of the population is heterozygous with a particular benefit (or past benefit) as a consequence.cheers,
M

Hi Crashfrog,
welcome aboard. Both you and Quetzal make excellent posts. As the majority of the genome does not code for proteins or functional RNAs, most mutations (outside of promoters, enhancers etc) will have no impact on fitness and are therefore neutral.Cheers,
M

Ok, here is a synopsis of the articles for the two papers that cannot be accessed for freePNASProc Natl Acad Sci U S A 2002 Oct 1;99(20):12949-54 Related Articles, LinksHitchhiking mapping: a population-based fine-mapping strategy for adaptive mutations in Drosophilamelanogaster.Harr B, Kauer M, Schlotterer C.Institut fur Tierzucht und Genetik, Veterinarmedizinische Universitat, Veterinarplatz 1, 1210 Vienna, Austria.The identification of genes contributing to the adaptation of local populations is of great biological interest. In an attempt to characterize functionally important differences among African and non-African Drosophila melanogaster populations, we surveyed neutral microsatellite variation in an 850-kb genomic sequence. Three genomic regions were identified that putatively bear an adaptive mutation associated with the habitat expansion of D. melanogaster. A further inspection of two regions by sequence analysis of multiple fragments confirmed the presence of a recent beneficial mutation in the non-African populations. Our study suggests that hitchhiking mapping is a universal approach for the identification of ecologically important mutations.The gist of this paper is that a beneficial mutation will be either lost or increase in frequency until it becomes fixed in the population. This is reflected genetically as reduced genetic variation at the beneficial locus and the flanking regions which lose variation due to "hitchhiking". This occurs because loci that are close to the beneficial locus will not undergo recombination as frequently as those more distant and therefore as variation decreases at the selected locus, the flanking regions lose variation as well. So non-positively selected loci and neutral genetic markers in their flanks such as microsatellite loci will show greater variation in a population than those under selection. This group screened a high density map in African and non-African Drosophila populations for signs of positive selection accross 850 Kb of DNA. What they found was evidence of several selective sweeps in colonizing populations (non-African) Drosophila as a result of having shifted to new environments. In one of the regions two genes exhibited fixed differences (the cramped and syntaxin4 genes).[Thanks, much appreciated. --Admin][This message has been edited by Admin, 03-21-2003]

The Payseur and Nachman paper is basically the same thing as the PNAS paper on Drosophila but applied to humans. The main point of the paper is that while the differences observed wrt positive selection is observed in Drosophila and human populations, it is much harder to study in humans because the effective population of humans is several orders of magnitude smaller than that of D. melanogaster which has a huge impact on overall genetic diversity....nobody said it was easy. Of course, this is the same problem you have when looking for disease genes.

The study itself is Modiano et al., Nature, 414, 305-308 (2001). Abstract: (The 6's are supposed to be betas - beta chain of hemoglobin, that is, and there should be arrows after the "Glu")
A Google search on "hemoglobin c" will turn up references to the health effects that it does have. The HbC allele has a "bulls-eye" distribution centered on Burkina Faso, and is thought to have arisen from a single mutation in the last 1000 years or so.

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.2) Why are there no Creationists in this thread?