The Nature of Mutations

Hey, don't worry about the mid game score! It's the score when the whistle blows that counts.It's fun to see what issues are under discussion and who's ahead at any given time. Now the points can be updated.And thanks for the effort, bye the way.[This message has been edited by NosyNed, 04-24-2003]

Nucleotide sequences in an organism that were not inherited from its parents. This includes differences that are the result of copy errors during meiosis of gametes in the parents.Does that sound about right to the biologists? I'm trying to get a kind of semantics-proof definition, here. Comments welcome.

Phospho's "rebuttal" to the RNASE mutation is in error. He misunderstands "adaptive" as meaning "non-random" rather than "beneficial". As his rebuttal rests on that error, it fails and the example remains unchallenged.

That is pretty much precisely as I would have proposed it. If the base pairs in a gene are altered in any way in passing from a parent to the offspring, it has mutated.FK

Hmm. In a sense, I suppose. However, technically there are two ways variation appears in an organism/population: 1) mutation and 2) recombination during meiosis. They really are two distinct mechanisms. Recombination is NOT a mutation - it's simply the randomization of existing DNA when the chromosomes split and shuffle during normal sexual reproduction (gametogenesis). I'm not totally clear what Phospho is referring to, but when I used the terms it was in that sense.

The above is incorrect.The apoA-1 Milano mutation does not destroy the capability of forming HDL. In fact, the HDL (High densisty lipoprotein) formed with the mutated form of the expressed protein appear to be more effective at their task of removing cholesterol.My reference is: This is a study of the HDL particles formed by the mutated protein.It is certainly true that HDL counts are low, but since the HDL particles are more effective, it is unambiguously false to infer that the low HDL would lead to an early death in the absense of an anti-oxidant effect.The anti-oxidant effect is an additional benefit of the mutation, and cannot be a replacement for HDL particles, which are essential to the cycles of cholesterol transport in the body.I do not know why HDL counts are low, but one contributing factor may be that the mutated proteins form a dimer, which means that two protein molecules bind together and work as a unit. HDL particles require protein molecules to form. With the wild type, the HDL particles seem to come in two main sizes, using two and three monomeric protein molecules respectively. The mutated form works as a dimer, using one and two dimeric protein molecules respectively. This means that effectively the same number of monomeric protein molecules give a smaller number of HDL particles. The chemistry of body metabolism is extraordinarily complex, and this simplistic model is certainly not adequate as a real explanation, but it may be one contributing factor.So far, no negative effects of the mutation are known. Low HDL counts are not a negative effect, since the HDL is so much more effective. HDL is used for transport of "bad" cholesterol out of the body, and this occurs just fine in individuals with this mutation. The benefits of this mutation are not confined to the additional anti-oxidant effect, which is proposed as another benefit of the mutation.A study of this mutation is a useful way to appreciate just how intricate and complex is the human body. A new protein does not just have one effect; it gets added into the mix of metabolism and body chemistry, and changes can have many different consequences. This stands as an example of a "random" change in which the mutated protein fitted in very well, with a number of desirable consequences. Effectively, the mutation seems to give an immunity to heart disease.The talkorigins archive has a new FAQ available on this mutation, at Apolipoprotein AI Mutations and Information. I helped with this FAQ (not as an author, though I did write the glossary), and this post is based on my own direct investigations from the primary literature.[This message has been edited by cjhs, 04-25-2003]

Or even simpler: Mutation is a failure of the DNA repair mechanism that creates a change in nucleotide sequence. Since mutation can occur in both somatic and germline cells (although, for evolution, only germline are considered), the inheritance requirement in your definition may be misleading. This also allows you to skip neatly over the "are endogenous retroviral insertions mutations?", as well as the "recombination is a mutation" quibble.Quetzal the Semantics Policeman

That's good. I like it. I'll accept that definition.Any disagreements?

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]

Arrgh. So much for trying to come up with a simple definition. Is there any way to capture the idea of "mutation" without referencing inheritance (which was really my only quibble with the original posted by crash)? And do so in a way that makes sense in the context of the OP?Welcome back, O Hairy One. We've missed you... (Q has to go back to being careful about what he writes again. *sigh*)

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

What about larger scale mutations such as gene duplications or even whole genome duplications?

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.

When you say genetic *or* developmental what are you thinking of? Epigenetic factors such as histone remodelling and DNA methylation?
I dont think the science paper is available on line. Is this the paper you were thinking of about the 20,000 generations?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
http://link.springer.de/.../02/2423/s00239-002-2423-0ch.html

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.