The Nature of Mutations II

As I recall, Phospho claimed he was moving and did not know when he would return to posting. However, there were several issues raised that got most of the rest of us into an interesting discussion as to how does one define mutation....then as you mentioned, the thread was as-salt-ed.

Hi salty,
Let's try a different approach here.
First as a ground rule (no I am not an Admin and this is not a forum rule) to facilitate discussion, rather than making a broad statement and then referencing your entire manifesto or a chapter, paraphrase your reference in an attempt to support your point.
i.e. instead of the evidence for semi-meiosis is section V-2, state explicitly what in section V-2 you believe supports your claim.Now, to the subject at hand...how would you define mutation?cheers,
M

Hi WK,
The question I posted to salty was to see if he could respond as I believe (like with everything else) he has an esoteric concept of what mutations are. I am curious as to how he will respond if he actually makes a real attempt...stranger things have happened Regarding your definition, while I agree with it and is similar to what I proposed, we got bogged down in a discussion as to whether meiotic recombination should be included in the definition of mutation..and epigenetics also makes a concise definition rather difficult. The origin of the question was Phospho's assertion that no mutation can be beneficial...this was preceded by an erroneous definition that genetic mutations were a change in amino acids in proteins that rendered them disfunctional.cheers,
M

Hi WK,
Your definition is actually the most concise to come out of the two Nature of Mutations threads so in future discussion we should probably link back to your post.I noticed a slightly related issue arose in your debate with Symansu in the Free for All where he made some strange assertions about DNA not being a liquid, somehow related that statement to blending inheritence and concluded Darwin was wrong...I am paraphrasing the argument...his definition of mutation would also be enlightening..or at least humorous cheers,
M

Hi salty,
Still looking forward to your definition of mutation...but given your last post, I would ask that you make a more thoughtful answer than that which you just gave to Wounded King. You clearly did not read either of the references he provided and your answer was to claim you opinion was based on a "studied" judgement. Having not read the references of WK, how can your judgement be considered studied?In any case, please give us your "studied" definition of mutation. We can deal with micro and macro evolution later.cheers,
M

Hi salty,
Regarding Peter Borger, since you presumably have some contact with him on another forum, you could ask him to contact the Admins and request re-instatement. Perhaps he has done so and failed. but in at least one case a banned participant was allowed to return. I would support his return for my part.Regarding your mutation definition. You lost me in the second sentence i.e. "That does not mean that there was any change in what was already present" Does this imply that a single base change in a gene is not a mutation under your definition? Their was a base already present before the change i.e. a C-T transition. There was a C before the T. This is also a heritable change. Also, how is expression heritable? DNA is heritable as are certain methylation states of DNA i.e. genomic imprinting..but gene expression? I could be misinterpreting what you are saying. Regarding recognizable change...how do recognize a mutation that does not produce a superficial phenotypic change? Or how about mutations at currently neutral sites (I mean changes in DNA sequences)I look forward to your elaborating.cheers,
M

Hi salty,
I appreciate your attempt but you still have not defined mutation here or in your subsequent post. I assume you read my questions? You made statements about heritability but you disqualified mutations in DNA as mutations with your definition.What is derepression of expression? How is this heritable...the derepression is caused by?Could you please address what a mutation is so that we can proceed?Looking forward.
cheers,
M

There is a need to elaborate as I do not get your point and as this is a debate I wish to understand your point of view better so I can formulate my own responses based on what you are actually proposing...so bear with me in the interest of furthering the discussion.What does your example of the ice ages have to do with a definition of mutation?As I study extinction and particularly the late Pleistocene extinctions there was certainly a response to the environmental change and it was not merely extinction. The removal of mammoths from Asia and North America for example paved the way for the expansion of a lot of different animal and plant groups that had been excluded previously. As to behavioral evolution, there is good evidence that animals exposed to human hunting pressure do adapt from the stand there and get shot behavior you attribute to squirrels to run like hell when anyhting on two legs approaches..this has been documented for moose in particular.As to your squirrel example, if the number of squirrels getting hit by cars is not a strong enough selective pressure i.e. there has been no population crash as a result of cars, then they have nothing to adapt to...thus why should avoidance evolve if it does not confer a great enough benefit?In any case, getting back to the Nature of Mutations and molecular genetics, there is clear evidence that high doses of UV and other environmental factors are highly mutagenic i.e. can change DNA sequences. According to you this is not a part of the Nature of Mutations. Please elaborate.cheers,
M

Hi salty,
I am not attacking you regarding mutations or claiming that you deny they occur. I am asking for your definition of mutation which you still have not provided. This is not intended to make fun of you or antagonize you but in the now deleted thread, it turned out to be difficult for all of us to come up with a definition of mutation we could agree on. Thus, I am asking for your contribution to this specific issue. From any disagreements that may arise, we can continue the debate.I will state outright that I am hoping that this time our interactions will be more cordial and productive than in the past. Thus far I would say things are going a bit better and hope you would concur.Regarding sexual reproduction causing accumulation of deleterious genes, thus far there is only evidence counter to that hypothesis for exampleColegrave N.
Sex releases the speed limit on evolution.
Nature. 2002 Dec 12;420(6916):664-6.Peck JR.
Frequency-dependent selection, beneficial mutations, and the evolution of sex.
Proc R Soc Lond B Biol Sci. 1993 Nov 22;254(1340):87-92.Charlesworth B.
The evolution of chromosomal sex determination.
Novartis Found Symp. 2002;244:207-19; discussion 220-4, 253-7. Review.and from parasites,Proc R Soc Lond B Biol Sci. 2003 Jan 7;270(1510):19-28. Related Articles, LinksThe maintenance of sex in parasites.Galvani AP, Coleman RM, Ferguson NM.Department of Integrative Biology, University of California, Berkeley, CA 94720-3140, USA. agalvani@nature.berkeley.eduThe maintenance of sex is an unresolved paradox in evolutionary biology, given the inherent twofold fitness advantage for asexuals. Parasitic helminths offer a unique opportunity to address this enigma. Parasites that can create novel antigenic strains are able to escape pre-existing host immunity. Viruses produce diversity through mutation with rapid clonal proliferation. The long generation times of helminth parasites prevent them from adopting this strategy. Instead, we argue that sexual reproduction enables parasitic helminths to rapidly generate strain diversity. We use both a stochastic, individual-based model and a simple analytical model to assess the selective value of sexual versus asexual reproduction in helminth parasites. We demonstrate that sexual reproduction can more easily produce and maintain strain diversity than asexual reproduction for long-lived parasites. We also show that sexual parasite populations are resistant to invasion by rare asexual mutants. These results are robust to high levels of cross-immunity between strains. We suggest that the enhancement of strain diversity, despite stochastic extinction of strains, may be critical to the evolutionary success of sex in long-lived parasites.Regarding Meiosis 1 and II...why do you consider that it has nothing to do with generating haploid gamates when that is the actual outcome?However, if you tried to do some benchwork to test your hypothesis I am sure you would find welcome...you might be surprised..even some Darwinians might let you have some lab space... I would highly recommend trying in fact to gather some empirical evidence.cheers,
M

Hi salty,
Hopefully you will address the other points in my post as you only focused on one small part of my questions addressed to you.But regarding your reply and previous reply on meiosis,in humans, failure of reduction during meiosis is associated with diseaseEscalier D.
Genetic approach to male meiotic division deficiency: the human macronuclear spermatozoa.
Mol Hum Reprod. 2002 Jan;8(1):1-7. Review.Regarding why you do not have reduction division at each stage of meiosis...think a little bit about what the consequences would be over several generations for a DIPLOID organism.As to there not no organisms that evade this reduction...there are some that do all sorts of different things during meiosisGenetics. 1999 Jan;151(1):277-83. Related Articles, LinksProduction of fertile unreduced sperm by hybrid males of the Rutilus alburnoides complex (Teleostei, cyprinidae). An alternative route to genome tetraploidization in unisexuals.Alves MJ, Coelho MM, Prospero MI, Collares-Pereira MJ.Centro de Biologia Ambiental, Departamento de Zoologia e Antropologia, Faculdade de Ciencias, Universidade de Lisboa, 1700 Lisboa, Portugal.The hybrid minnow Rutilus alburnoides comprises diploid and polyploid females and males. Previous studies revealed that diploid and triploid females exhibit altered oogenesis that does not involve random segregation and recombination of the genomes of the two ancestors, constituting unisexual lineages. In the present study, we investigated the reproductive mode of hybrid males from the Tejo basin, using experimental crosses and flow cytometric analysis of blood and sperm. The results suggest that diploid hybrids produced fertile unreduced sperm, transmitting their hybrid genome intact to offspring. Triploid hybrids also produced unreduced sperm, but it was not possible to obtain data concerning their fertility. Finally, tetraploid hybrids produced fertile diploid sperm, which exhibited Mendelian segregation. Tetraploid R. alburnoides may reestablish biparental reproduction, as individuals of both sexes with the appropriate constitution for normal meiosis (two haploid genomes from each parental species) are likely to occur in natural populations. Tetraploids probably have arisen from syngamy of diploid eggs and diploid sperm produced by diploid hybrid males. Diploid hybrid males may therefore play a significant role in the dynamics of the complex, starting the evolutionary process that may ultimately lead to a new sexually reproducing species.

and another reference i just foundGenome. 1997 Jun;40(3):397-405. Related Articles, LinksSex and meiosis in autotetraploid Pacific oyster, Crassostrea gigas (Thunberg).Guo X, Allen SK Jr.Haskin Shellfish Research Laboratory, Rutgers University, Port Norris, NJ 08349, USA. xguo@hsrl.rutgers.eduSex and meiosis were studied in induced autotetraploids of the Pacific oyster (Crassostrea gigas Thunberg) and were compared with sex and meiosis in autotriploids and normal diploids. Tetraploid oysters reached sexual maturity at 1 year of age in an approximately 1:1 sex ration. In contrast with the abnormally high frequency of hermaphrodites among triploids, tetraploids had about the same level of hermaphrodites as normal diploids. Fecundity of tetraploids was comparable to that of normal diploids, differing from the greatly reduced fecundity of triploids. Homologous chromosomes synapsed predominantly as trivalents in eggs from triploids and as quadrivalents in eggs from tetraploids. After fertilization, eggs from tetraploids and triploids went through two meiotic divisions, as normal eggs did. The average gamete chromosome number was 10.0 for diploids and 19.9 for tetraploids. The distribution of gamete chromosome numbers from triploids suggested that the extra chromosome in the trivalent segregated randomly during anaphase I. In tetraploids, however, the two extra chromosomes in the quadrivalents did not segregate independently and, instead, they preferentially cosegregated to opposite poles producing balanced gametes. These results suggest that mechanisms may exist to weight, balance, and equally distribute quadrivalents, possibly through mitotic force and tension. Errors in chromosome balancing in normal meiosis may result in nondisjunction, which is the primary cause of human aneuploidy.

Hi Salty,
I hope you will address the questions I had for you regardless of whether or not you are angry with Scott or not. Think of it this way, you don't approve of Peter Borger not being allowed to post here (I agree with you that he should be allowed) but how would it be any different if Scott was not allowed to post? If it is to be an open forum you have to tolerate opinions and even people you do not like.Though you apparently did not like the tone of his post, Scott brought up very good questions that you did not address.Take a breather, come back with a response to the remaining questions, post some questions to Wounded King and myself (if you have any) and let's continue.cheers,
M

Good point WK...if it is a heritable structural abnormality i.e. the structure is passed on though it is perhaps only partially penetrant I guess it would have to be considered a mutation by the definition you posted at the beginning of the thread.Though I will have a hell of a time finding the reference since I read the paper about 12 years ago when I will still a Ph.D. student, I remember a really bizarre phenomenon in mice that I am not sure how to classify. Apparently, if a female fetus developes between two males in utero, it increases to a statistically significant degree the chance that she will produce male embryos. If between two females she will produce 50:50. I recall there is a similar phenomenon in cattle..Freemartin cattle or something like that....sorry that this is so half-baked but I read it a really long time ago and it came to mind this morning. But this is a non-genetic affect like a maternal effect in Drosophila but it has a phenotype that can be passed on...sort of....oh well, the clarity of this post would probably have improved if I had not had that last beer last night..or the first one either

Hey, you found it I did a quick NCBI search and did not turn it up. Thanks. As I feared, my memory failed me and I had thought that the effect was transmitted to the F2 generation of mice i.e. skewed sex rations in the pups of the 2M female pups...but it is not and it is a simple enviromental effect. Though, it is the transmission of a phenotype from mother to offspring via the in utero environment...I would say this is not a mutation even though it involves gene expression and altered phenotype.Another, strange phenomenon in mice that can have profound effects on the population is the t-complex involved in meiotic drive. The t-complex is transmitted as a unit and once it enters a population it sweeps through it...thus, unlike a classical point mutation with a selective benefit or recombinant etc. it is a selfish locus. It is like a heritable mutation of the more general variety but t-complex bearing sperm appears to actually destroy non-t-complex sperm and thus selects itself for propagation...really strange "mutation"Proc R Soc Lond B Biol Sci. 1993 Jul 22;253(1336):83-91.
A model for the mechanism of transmission ratio distortion and for t-associated hybrid sterility.
Hurst LD.
Department of Zoology, Oxford, U.K.A mechanistic model is presented to account for the action of t-complex of mice. This model takes account of recent evidence suggesting that t-complex distorters are amorphs or hypomorphs. Following Lyon's (Genet. Res. 59, 27 (1992) scheme, the model proposes that the t-complex distorter (tcd+) loci for normal function than does the wild-type form of tcr. However, a tradeoff against this ability to drive is a reduced efficiency of the haploid specific product of tcrt in the absence of drive. Regulation of tcr could be achieved by differential splicing or post-translational modification under the control of the t-complex distorters. It is shown that the model is consistent with known fertility and distortion data, as well as with the finding that the mechanism of drive is intimately connected with the mechanism of intraspecific homozygous sterility. Importantly, the model predicts that the mechanism of hybrid sterility associated with the t-complex is the same as the mechanism of intraspecific homozygous sterility. If accepted then this will be, to the best of the author's knowledge, the first description and characterization of a Haldane rule sterility gene. The new understanding of the mechanisms of t-complex shows its mode of operation to be fundamentally different to the only other well-described autosomal meiotic driver, Segregation Distorter (SD) of Drosophila melanogaster.Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6851-5.
Evolution of the mouse t haplotype: recent and worldwide introgression to Mus musculus.
Morita T, Kubota H, Murata K, Nozaki M, Delarbre C, Willison K, Satta Y, Sakaizumi M, Takahata N, Gachelin G, et al.
Department of Microbial Genetics, Osaka University, Japan.Mouse t haplotypes are variants of chromosome 17, consisting of four inversions. Despite the homozygous lethality and pleiotropic effect on embryonic development, sperm production, and recombination, they have widely spread in natural populations of the house mouse (10-40% in frequency) because of the meiotic drive advantage. We sequenced 14 Tcp-1 (t-complex polypeptide 1) genes from four t haplotypes, nine wild mice, and a rat as a reference. From a comparison of intron sequences of 610 base pairs, we dated the origin of t haplotypes to 2.9 +/- 0.7 million years ago, which predates the splitting of Mus musculus subspecies (approximately 1 million years ago). However, the Tcp-1 intron sequences of t haplotypes from different M. musculus subspecies from various parts of the world show no divergence, indicating the recent introgression (no earlier than 0.8 million years ago) of a single ancestral type. Nucleotide changes in coding regions are also consistent with this conclusion. Hence, polymorphisms among t haplotypes including lethality factors have accumulated during this short time period independently in each M. musculus subspecies.

Hi salty,
Private emails are fine, but the purpose of the forum is to have lots of people debate a subject with additional people reading the debates though not contributing. Because of the nature of the subject, there is often hostility between people. You and Scott obviously, from multiple forums and websites, do not get along. But you should realize that there are lot more people here than just the two of you. And I was under the impression you wanted to discuss your ideas with the widest audience possible?Admin, Wounded King, and I have not denigrated you or attempted character assasination. So why not focus on our respective conversations and ignore taunts that come your way?cheers,
M