The Nature of Mutations

I prefer FK's post 64 (sorry Quetzal ). Polymerases have misincorporation rates that vary from rather high, such as most reverse transcriptases, to very low, like some modified versions of Taq polymerase used in PCR. This instigates some mutations so it would not be technically accurate to place the origin of the mutation from the failure of DNA repair...especially in mitochondria for example, which have rather poor DNA repair capacity relative to nuclear DNA.I would also point out another source of mutation which is epigenetic i.e. DNA methylation or histone acetylation which can supress gene expression among other things. Errors in DNA methylation are proposed as one of the key reasons mammalian cloning fails so often even though the DNA sequence is unaltered.Also in the mutation definition why exclude recombination? If two sequences recombine and generate a novel variant, that is also a mutation. The genome is littered with solo LTRs (9% of the human genome from endogenous retroviruses alone) that arise due to recombination events that remove the intervening proviral sequences. Selection can act on novel recombination derived variation.Whether a mutation is beneficial, deleterious, or neutral based on environment is another question and is subject to quite a few variables. Phospho's assertion that all mutations are lethal is just plain wrong...otherwise we would all be invariant clones...actually we would not be here at all if genetics were so constrained.[This message has been edited by Mammuthus, 04-25-2003]

Hi QIf we want to keep it simple for the purpose of this dicussion I would take Fedman Kassad's post 64 definition where any base pair difference between parent and offspring. You could elminate inheritance from this definition by applying it to somatic DNA differences i.e. karyotpye rearrangments in cancer to point mutations which will obviously not be inherited.Otherwise I cannot see ways of simplifying the definition. I can only think of ways to make it more complicated such as purely environmental effects that change gene expression during development like maternal effects in Drosophila...a slightly different timing of Hox gene expression could lead to a large phenotypic difference without any change in the underlying gene sequence....sorry, I find it hard to be reductionist

Yup, that to would count.Actually, any variation genetic or developmental will, will be acted upon by selection under certain conditions.As to the concept of beneficial mutations, here is a paper that was rather controversial from a group that studied both adaptation and punctuated equilbrium using bacteria over many generations.Elena SF, Cooper VS, Lenski RE.
Punctuated evolution caused by selection of rare beneficial mutations.
Science. 1996 Jun 21;272(5269):1802-4.Since this paper was published they have gone futher studying bacterial populations for as many as 20,000 generations to really look at the effects and distribution of adaptive mutations in populations.I am assuming this article can be accessed without a subscription but I could be wrong.

Hi WK,"When you say genetic *or* developmental what are you thinking of? Epigenetic factors such as histone remodelling and DNA methylation?"M: Exactly what I mean...or stochastic events i.e. why cloned cows have differing coat color patterns etc."I dont think the science paper is available on line. Is this the paper you were thinking of about the 20,000 generations?"M: Grrrrr I really hate the publisher's policies...our research is already mostly taxpayer supported and then they can't even make a 1996 paper freely available!"Lenski RE, Winkworth CL, Riley MA.
Rates of DNA Sequence Evolution in Experimental Populations of Escherichia coli During 20,000 Generations.
J Mol Evol. 2003 Apr;56(4):498-508.
Available online (not sure of subscription status) at"M: Yes, this is one and thenCooper TF, Rozen DE, Lenski RE.
Parallel changes in gene expression after 20,000 generations of evolution in Escherichiacoli.
Proc Natl Acad Sci U S A. 2003 Feb 4;100(3):1072-7.Cooper VS, Bennett AF, Lenski RE.
Evolution of thermal dependence of growth rate of Escherichia coli populations during 20,000 generations in a constant environment.
Evolution Int J Org Evolution. 2001 May;55(5):889-96.Riley MS, Cooper VS, Lenski RE, Forney LJ, Marsh TL.
Rapid phenotypic change and diversification of a soil bacterium during 1000 generations of experimental evolution.
Microbiology. 2001 Apr;147(Pt 4):995-1006.

I can't really test it to see. We have an institution online subscription so I can automatically access all Science articles that are online including archived materials.Somebody who has no Science subscription please try to access this article...I'm curious if it works...the entire open access business has been controversial.

How about restricting the definition to genetic mutations? Epigenetics, etc. could get their own topic at some other point but for the purpose of this thread, any difference between parent and offspring DNA would be a mutation regardless of the mechanism i.e. recombination, improper base excision repair, polymerase error etc etc.

Ahhhh...try to make it simple and everybody complicates things What the heck..let's say that is a mutation as well.

Upon further thought, I guess we don't want to consider the sum total of the new offspring's genome a mutation though some parents I have met would beg to differ Maybe it should be limited to point mutations for this discussion? Or only include recombination events that produce novelties not present in any form in the parental genomes i.e. a trinucleotide repeat expansion via unequal crossover or additional copies of rDNA genes produced during meiosis...that as opposed to a general meiotic recomination event as you state.Your turn Quetzal...so that I have a chance to make it complicated again

Hi Q,
I was not trying to limit it to point mutations. I just wanted to avoid calling the results of sexual recombination mutants or mutations as that would be about as unhelpful as the Semi-Meiotic hyphothesis . The definition you dug up looks to be suitable for the purpose of this thread..what was the topic again ?The one problem with the definition is the vagueness regarding "changes in gene expression"...it covers epigenetic modification but does not account for variation induced by environment which is not really a mutation. I am thinking of variation in coat color in cloned cows or variation in paternal or maternal X chromosome inactivaition in female embryos which are driven by purely stochastic events....but I guess that is covered since the definition says heritable change.So regarding definitions...do we have a winner? crashfrog, Fedmahn, Percy, Nosyned..comments, disagreements, additions?cheers,
M

Thanks for responding guys. Now with a definition of mutation in hand maybe we can proceed with more of what PLG posted...as several have noted, he bolted and may or may not come back. But the thread is interesting so I for one would like to continue...PLG:
Evolutionary theorists favorite mutation to quibble about is the sickle cell anemia mutation...this is a deleterious mutation by catagory. It damages the cells to the point that they cannot function as they were intedned to function, they have been damaged. True, that in certain areas this gives the seeming benefit of conferring "resistance" to those affected with the mutation, but this does not erase the damage that the person sustains due to that mutation.M: This is a rather odd way of looking at things. PLG ultimately does not want to concede that mutations can confer any benefit but he ignores the meaning of beneficial in the context of natural selection. Sickle cell heterozygotes can survive and are more resistant to malarial infection than normal individuals. Thus, the detrimental effects of the slight sickle phenotype are outweighed by the benefits (RELATIVE to wild type) of malaria resistance...thus heterozygotes have a better chance of reproducing and the sickle mutation is maintained in the population. In a non-malaria environment the mutation would likely be weeded out quickly as homozygotes and heterozygotes would be at a great disadvantage. Ultimately, the heterozygous state of the sickle cell trait IS beneficial.PLG:
Second, it has not been proven anywhere at any time to my knowledge that variation arises from mutations. This is part of the grand assumption that evolution is a fact and, therefore, the naturalistic paradigm demands endless variational changes, so theorists assume it into the equation. This is why it is called a "gene pool" and not a "gene stream" because there is NOT an endless supply of variation streaming into the genome of species.M: This makes no sense whatsoever. If I have an C at a particular position in my mitochondrial D loop and PLG has a T at that position, this is part of the genetic variation of the human mitochondrial gene pool and it directly derives from a mutation event. This is the case for all mutations. If genetic variation does not derive from mutation then why are we not all clones?PLG:
Without endless variation, you have no evolutionary change. Adaptational changes in organisms are due to changes in gene expression by environmental ques, and are not due to mutations.M: This is also completely false. One does not require endless variation for evolutionary change. In fact genetic drift which reduces variation can do as much for evolutionary change as increase in mutation accumulation in a large population.
Adapatational changes are not a mere response of genes to environmental queues unless PLG is proposing Lamarkian molecular biology. Changes in promoter sequences have more to do with changes in gene expression that are adaptive...and for more on adaptive mutations:Elena SF, Cooper VS, Lenski RE.
Punctuated evolution caused by selection of rare beneficial mutations.
Science. 1996 Jun 21;272(5269):1802-4.PLG:
All of your examples of bacterial adaptation that I have come across to date are just that, changes in gene expression, from inactivated to activated sites. Nothing more. I also find it hilarious that after touting that evolutionary change takes hundreds of thousands of years to take hold, now suddenly we can take a bacteria and bring about evolutionary changes in months. This is not evolutionary change, this is adaptation.M: First he says there are no examples of bacterial adaptation and then it is only adaptation...in any case, the above reference demonstrates that this statement is false. I have posted other references from the same and other groups that experimentally show that it is not changes in "activated or inactivated sites"...whatever that means. In any case, evolution takes thousands of years to observe in organisms with long generation times...like mammals. Bacteria do not have this constraint and thus we can observe many thousands of generations (Richard Lenski's group is up to 20,000 generations and counting) and hence evolution in action. If you try to do the same with say elephants with an 18 month gestation period you better be immortal to see the outcome of the experiment.PLG:
And adaptation is not evolution, it is not speciation. It is change, but if you are going to go to that silly and ridiculous length to try to prove evolutioanry theory, then we better start calling every single kind of change in the all of all as evolution.M: Another strange statement and a misunderstanding of evolution...from your basic evo textbook"In the broadest sense, evolution is merely change, and so is all-pervasive; galaxies, languages, and political systems all evolve. Biological evolution ... is change in the properties of populations of organisms that transcend the lifetime of a single individual. The ontogeny of an individual is not considered evolution; individual organisms do not evolve. The changes in populations that are considered evolutionary are those that are inheritable via the genetic material from one generation to the next. Biological evolution may be slight or substantial; it embraces everything from slight changes in the proportion of different alleles within a population (such as those determining blood types) to the successive alterations that led from the earliest protoorganism to snails, bees, giraffes, and dandelions."
- Douglas J. Futuyma in Evolutionary Biology, Sinauer Associates 1986So, PLG or any other creationist want to pick up this argument?Anyone else feel free to add to, criticize or otherwise comment.cheers,
M

Hi PLG,I am assuming you have access to some of these articles..please indicate if you do not.PLG: First, where is there any evidence that mutation gives rise to variation? There is none. Provide that which you call evidence, and I will demonstrate that it is only transposon-activated genes that before hand were dormant and non-expressed.M: cases where transposons activate genes or influence their transcription is relatively rare. If you have references to the contrary please post them. The last one in particular negates your position as they deal with adaptation via point mutation in a study encompassing 20,000 generations of bacterial evolution.mutation is the only way of giving rise to genetic variation...note, this list is extremely limited and meant only as an example...one could probably jam the server posting all the literature on genetic mutation research even excluding that involving transposable elements.Enard W, Przeworski M, Fisher SE, Lai CS, Wiebe V, Kitano T, Monaco AP, Paabo S.
Molecular evolution of FOXP2, a gene involved in speech and language.
Nature. 2002 Aug 22;418(6900):869-72.Britten RJ, Rowen L, Williams J, Cameron RA.
Majority of divergence between closely related DNA samples is due to indels.
Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4661-5.Britten RJ.
Divergence between samples of chimpanzee and human DNA sequences is 5%, counting indels.
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13633-5.Lenski RE, Winkworth CL, Riley MA.
Rates of DNA Sequence Evolution in Experimental Populations of Escherichia coli During 20,000 Generations.
J Mol Evol. 2003 Apr;56(4):498-508.

Hi PLG,
I don't think your messages have been rude or out of line so no problem from my point of view...the thread has been pretty interesting.As to epigenetics, it is a reasonable question and someone else asked what it was a few days ago.Below is a review containing the abstract...I don't think it fits with what you are trying to get across. Methylation is a reversible process that shuts down or turns on genes for example in female mammals the one of the two X chromosomes is inactivated to compensate for the dose of genes relative to males who have one X chromosome. There are autosomal genes where one allele is shut down by methylation so called imprinted genes. This is a consistent form of gene regulation, not a mutation. It is also largely a stochastically driven process i.e. 50:50 chance which X chromosome is inactivated in a given cell. This is not a deterministic mutation mechanism for driving evolution as you seem to be defining mutation. Nor are transposable elements relevant to epigenetics as you have described.Electrophoresis 2001 Aug;22(14):2838-43
DNA methylation and mammalian epigenetics.Reik W, Dean W.Laboratory of Developmental Genetics and Imprinting, The Babraham Institute, Cambridge, UK. wolf.reik@bbsrc.ac.ukEpigenetic modifications of DNA such as methylation are important for genome function during development and in adults. DNA methylation has central importance for genomic imprinting and other aspects of epigenetic control of gene expression, and during development methylation patterns are largely maintained in somatic lineages. The mammalian genome undergoes major reprogramming of methylation patterns in the germ cells and in the early embryo. Some of the factors that are involved both in maintenance and in reprogramming, such as methyltransferases, are being identified. Epigenetic changes are likely to be important in animal cloning, and influence the occurrence of epimutations and of epigenetic inheritance. Environmental factors can alter epigenetic modifications and may thus have long lasting effects on phenotype. Epigenetic engineering is likely to play an important role in medicine in the future.

Hi PLG..An even better review of epigenetics and evolution...unfortunately Nature Reviews Genetics requires a subscription...but you can get it in most university libraries with a bio department.Nature Reviews Genetics 4, 359-368 (2003)WHAT GOOD IS GENOMIC IMPRINTING: THE FUNCTION OF PARENT-SPECIFIC GENE EXPRESSIONJon F. Wilkins, & David Haig1 Society of Fellows, 7 Divinity Avenue, Harvard University, Cambridge, Massachusetts 02138, USA.
2 Bauer Center for Genomics Research, 7 Divinity Avenue, Harvard University, Cambridge, Massachusetts 02138, USA.
3 Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts 02138, USA.correspondence to: Jon F. Wilkins jwilkins@cgr.harvard.eduParent-specific gene expression (genomic imprinting) is an evolutionary puzzle because it forgoes an important advantage of diploidy protection against the effects of deleterious recessive mutations. Three hypotheses claim to have found a countervailing selective advantage of parent-specific expression. Imprinting is proposed to have evolved because it enhances evolvability in a changing environment, protects females against the ravages of invasive trophoblast, or because natural selection acts differently on genes of maternal and paternal origin in interactions among kin. The last hypothesis has received the most extensive theoretical development and seems the best supported by the properties of known imprinted genes. However, the hypothesis is yet to provide a compelling explanation for many examples of imprinting.

Hi Wounded,
It is just the parental conflict hypothesis with a different name..I don't know why they did not refer to it as such in the abstract as in the text they do.."and the kinship theory proposes that imprinting has evolved because of an evolutionary conflict in individuals between maternally and paternally derived alleles8."Reference 8 on kinship theory is
8.
Haig, D. Genomic Imprinting and Kinship (Rutgers Univ. Press, New Brunswick, 2002).
A collection of papers that trace the development of the kinship theory, with retrospective commentaries.cheers,
M

Greetings PLG,quote:
--------------------------------------------------------------------------------
PLG ultimately does not want to concede that mutations can confer any benefit but he ignores the meaning of beneficial in the context of natural selection.
--------------------------------------------------------------------------------This is not so, please read my posts again.M: I have and this is my interpretation..I will elaborate belowPLG: More side-tracking. The issue is not one outweighing the other, the issue is not so much even the effects of the mutation. Although they do play a part in this because the catagories of mutation are specified by their neutral or deleterious affects. The issue is the NATURE of mutations...what they are, and what they are not.Again, some, very rare deleterious mutations have proven that they can, in certain environments, confer some amount of beneficial side-affects to their bearer. But then again, this is not what I am arguing.M: wrong, the entire issue is the effect of the mutation. If a C to T transition in the Dloop of mitochondria has absolutely no effect on mtDNA replication, mitochondrial gene expression, etc. then the mutation is irrelevant as it has no effect on the organism. It is neutral with regards to evolution. However, any mutation that under a specific environmental condition ehances and indivduals chance at reproduction has a better chance of becoming more frequent. So not all mutations are deleterious...what does it matter if a pseudogene has a C or a T at a given position?PLG:Is this your reasoning for accepting that variation arises from mutation? If so, it is poor reasoning...no insult intended. We are not clones because we did not all come from the same egg. As for other arguments along that line, even identical twins have differences in expressed variant alleles...in short, no one is exactly identical. Even twins have different finger prints, this much I can attest to.M: You are confused PLG, you are talking about non-heritable variation during developement which is responsible for differences among twins. We are not clones because of heritable genetic variation. Thus, the source of heritable variation IS genetic. That is not a strictly evolutionary concept as all genetics relies on this.PLG:
Not so, evolutionary theory needs variation, otherwise it goes no where. There are plenty of top evolutionists that disagree with you, Mayr, for one. As for genetic drift, another false play by evolutionary theorists of the last century, has nothing to do with evolutionary theory. It has to do with population genetics, which also has nothing to do with evolutionary theory.M: You are completely wrong on two fronts. First, I said one does not need endless variation for evolution to occur..not that variaition is uneccessary..Please read my posts more carefully as I was addressing your statement.Population genetics and evolution are the same thing. That you deny this suggests you are either poorly informed about evolutionary biology or someone has purposefully mislead you...Here..from a basic biology textbook for your edification"In the broadest sense, evolution is merely change, and so is all-pervasive; galaxies, languages, and political systems all evolve. Biological evolution ... is change in the properties of populations of organisms that transcend the lifetime of a single individual. The ontogeny of an individual is not considered evolution; individual organisms do not evolve. The changes in populations that are considered evolutionary are those that are inheritable via the genetic material from one generation to the next. Biological evolution may be slight or substantial; it embraces everything from slight changes in the proportion of different alleles within a population (such as those determining blood types) to the successive alterations that led from the earliest protoorganism to snails, bees, giraffes, and dandelions."
- Douglas J. Futuyma in Evolutionary Biology, Sinauer Associates 1986PLGopulation genetics only traces the differences in expressed variant alleles within populations, and that is all.M: Wrong again, population genetics does not trace differences in "expressed" variant alleles. The majority of population genetic markers are non-expressed. Are you sure you know anything about pop gen? Just asking..have you ever taken a course? Read a textbook? Primary literature? I ask because you are making definitive statements that are completely false.PLG:
Evolutionary theory is not about variation, it is about speciation (and with that we open up another can of worms).M: Uh, you have not read Darwin either it seems. Evolutionary theory is exceptionally pre-occupied with variation and how said variation is acted upon by selection resulting in (mostly extinction actually) but also speciation.PLG:
This was my first clue that something was amiss with the theory, everytime I came up to a pivotal point in one portion of evolutionary explanations for proving evolution true, there came a road block. At that roadblock, there magically formed an assumption to overthrow that blockade...answer this, please...M: Because that is how science works. All theories, gravity and relativity for example are tentative. They are constantly being tested and modified as novel discoveries are made. A theory can be overthrown. Evolution is the best supported theory in biological science but is still tentative. You will no more "prove" evolution as you will "prove" the theory of gravity. Assumptins are not magically formed by the way...at least nobody has ever accused me of performing magic in the lab..especially when I drop my tube rack on the floor...doh!PLG:
Pure beneficial mutations are assumed, why? Because without mutations you have no variant alleles. Why does evolution need variant alleles? Because variants are differences between organisms.M: You were doing a bit better up to this point...PLG: But variation does not give rise speciation...since when has one creature ever been observed to change into another creature?M: one creature does not turn into another....Lamark was wrong.However, variation in populations does give rise to new species and this has been observed in the case of bacteria, cichlids, and in various plants among other things.PLG:
So, we have to come up with a definition of speciation that demonstrates evolution is a reality, and so Mayr has...in his own mind, anyway. However, none of these examples change one creature into another, they only demonstrate variation.M: Again, your logic is flawed and also demonstrates you have no grasp of the scientific method.PLG:
We have come up against another wall, so we assume that with enough micro variation, we will eventually observe macro variation...speciation. This is not the case. We have now jumped over what the factual data will allow with invalid and unwarranted assumptions four times, and it is interesting to me that at every wall is when these assumptions are called upon. Then we call upon another one, the assumption that evolution is simply change, this way we can call upon population genetics to demonstrate evolution, but does it really?M: Firs n genetics demonstrates evolution very well in fact..here are just two examples of manySchliewen UK, Tautz D, Paabo S. Sympatric speciation suggested by monophyly of crater lake cichlids.
Nature. 1994 Apr 14;368(6472):629-32.Lenski RE, Winkworth CL, Riley MA.
Rates of DNA Sequence Evolution in Experimental Populations of Escherichia coli During 20,000 Generations.
J Mol Evol. 2003 Apr;56(4):498-508.PLG:
No. It does not demonstrate nor observe one creature turning into another, it only documents variational differences. If we reduce the theory of evolution to what some call micro-evolution, changes within organisms'expressed allelic gene versions, then I agree. But until it can be demonstrated that we have one organism turning into another, there is no evolutionper say. Darwin did not give a thesis on trying to explain variation, but on the divergence between a modern dog and its ancestors. Between a modern elephant and its ancestors, etc.M: This is a typical creationist rant that one organism turning into another which evolution and genetics do not propose. This is neo-Lamarkian thinking and is thus a strawman arguement against evolution.
Find a definition by an evolutionary biologist or geneticist that claims one organism turns into another...your are describing the typical cartoonish version of science uneducated creationsists adhere to.PLG:In short, unless you have a genetic mechanism that can add to a single celled organism, that in time will build blue-prints for arms, legs, sex organs, other organs, a head, mouth, fingers, etc....M: Actually there is...they are called Hox genes...I can't believe you have never heard of this PLG:
you have no evolution. My argument is this, that there is no such mechanism.M: Your argument is refuted by developmental genesPLG:
All of the supposed "mutations" that I have read in papers have to do with variation adaptation to nylon, or mosquito resistance to DDT are not true mutations. They are only genetic changes induced in one way or another by the organisms cellular or sub-cellular systems. They are not mutations by nature.M: You clearly do not know what a mutation is. So genetic changes leading to an altered phenotype is not mutation?...that will be news to the entire scientific community....please cite the papers you have read by the way so that we can discuss these supposed cellular or sub cellular system changes you claim there is evidence for.PLG:My whole argument, boiled down, I guess, is that what scientists are calling as mutations today are fabrications and mis-callings based upon what the evolutionary theorists of yester-year propagandized the to be in their efforts at keeping the theory alive. What needs to be done is this, these areas need to be looked at again, from the very beginning, identifying these assumptions that are holding the theory together (many and unfounded are they), and test them. But for now, there are just too many, even by science's standards [Kitcher], for the theory of evolution to be considered a valid theory.M: Sorry that my tone is turning snide but you apparently have no background in biology and yet are attempting to make difinitive statements about biological phenomenon.So, your argument boils down to what a geneticisit calls a mutation is a lie propagated by the scientific community to mislead people like you? That is a weak and frankly a paranoid argument.I am not convinced you have any knowledge of what a mutation is or what evolution is..Please define what you think is the scientific and generally accepted (in the scientific community) definition of
1. Mutation. Please provide supporting references for your definition
2. Evolution. Also provide supporting references and in addition please demonstrate how the definition I provided by Futuyma is false and is not accepted by scientists.This should be an easy task considering you claim to be an authority on mutation and evolution.Looking forward to it...Cheers,
M