Non-mendelian genetics/ non-darwinian evolution

WK,I understand your point more given that you consider HGT a form of inheritance, rather than a form of mutation. I think of 'inheritance' as occuring only within species, from parent to progeny as a result of reproduction. Any genetic insult to an organism (HGT included) is a form of mutation, that is subsequently inherited by its progeny.I'm not sure why considering HGT a form of 'mutation' makes the concept meaningless for molecular biology - mutation already has quite a broad definition I would argue, essentially defined as any sequence level change to the genome.I also feel that transposons bopping around within a genome could easily result in non-Mendelian inheritance, since their exit/entry sites could be differently and unpredictably inherited across progeny and generations, resulting in inheritance of different alleles... (hopefully that makes sense).

WK writes: A clarification that may go a long way to defining this discussion:Are we discussing "Mendelian inheritance" of phenotypes or genotypes?

Pink: 1) I do not argue with the fact that "mechanistically" the way in which a gene is inherited is Mendelian! (thought I had gotten that across the first post I made?)
2) However, the fallout expectation that many (which was one of the main points I felt WK was making in bringing this up) who are not neck deep in this stuff is a simple 'if you have this genotype then you have this phenotype'...because this is what people will remember from their science class if they took one. As you know the simple-ness of it all is what gets played on by creationists and others that are not in the field. So, I do think some re-vamping is in order.
3) The reality? You can put whatever gene you want there but epigenetics will weigh in on how the gene gets expressed, if it is, as well as ALL of the other factors I mentioned previously.
Ethnicity:To put this in context: My point was supposed to be that despite the Mendelian segregation of gene A which contains a SNP that is in LD with a couple of other SNPs and in Western European's it is not only highly associated with Asthma, but many other markers of the disease.....the association is gone when you look at an Asian population, for example. Despite Mendelian genetics "at work" you get two different phenotypes.
Anyway, I think it's moot as WK seems to be looking for non-Mendelian in the context of mechanistic not interpretation.

To some extent we're arguing in circles, it sounds like in part you are frustrated that most people you deal with don't understand QTL/association studies, and thus a popular (incorrect) understanding of Mendelian inheritance is what you are rallying against.Your statements themselves leave you guilty of being 'genetically misleading', since your statements leave the impression that ethnicity is somehow a factor, when it is not at all - in association studies it is simply a (sloppy) way to control for genes and environment, the true factors.In most association studies, SNPs are often NOT functional polymorphisms and rather just markers for them. In any case, if specific 'asthma' genes are identified, they'll play a role in airway constriction in any population, though not necessarily a pathological role, which may only emerge in the proper genetic background and environment.If someone believes the state of a few SNPs will absolutely determine a complex phenotype despite environmental and genetic background effects, that is ignorance, not a violation of Mendelian inheritance.As far as revamping education, like I said previously, I was taught the genetics of complex traits, first in 7th grade (height), again in 9th grade, and repeatedly in college (including complex disease). It sounds like you had a different experience...To some extent we should be happy if the average high school graduate understands what a gene is, and how it works - most MDs and PhDs in biomedical research I know don't have a real grasp of complex trait genetics, so if you come up with a way for high school students to understand it, more power to you.What percentage of Americans could tell you what a gene is and what it does? Who Mendel was? What his experiments were? Let alone what impact they have on human disease?Maybe I'm sounding a bit pessimistic, but I don't believe that the average American, or even the average scientists, should understand genetics beyond a simple level, unless they are interested. Do you have a complete grasp of complex immunology? neurology? protein regulation? cancer biology?Should everyone?

Genotypes would be my preference.TTFN,WKP.S. I'm still thinking, unforunately I actually have to do some work today, anyone reccommend a good method of searching for specific transcription factor binding sites in a sequence almost a megabase long?

Try Genomatix and the program MatInspector. I think as an academic institution you can access it for free, or at least do a limited use trial.

Yeah, I got the sense we were entering a round-about at the end of my last post. My take on the initial post was that WK was interested in getting a re-vamping as well, so I don't think I am alone in this "frustration".
1) Ok, drop the ethnicity thing...you, and maybe others, misunderstood my intent.
2) First of all, with the limited number of labs doing ACTUAL functional studies on SNPs (I work in one) you are overstretching your statement, because in fact you cannot say "SNPs are often NOT functional polymorphisms and rather just markers for them." at this point. Well, that seems to be what the majority do think. Btw, I'm sure you'll correct me if I'm wrong, I don't think Mendel EVER said anything about the role of environment on inheritance, so your implication that it's covered and simply someone else's misunderstanding of Mendelian genetics is inaccurate. And this is absolutely the reason why I am against looking at evolution based on a neutral DNA model. Because the underlying statement is that just because the gene is there or not means you get the exact same phenotype through time.Anyway, I think you and I have kicked this dead horse enough.-Cheers

It makes mutation meaningless for molecular biology because it covers such a broad spectrum. It may still be useful for organismal and population genetics levels, but if a mutation covers anything from a synonymous point mutation to a large scale rearrangement of the chromosomes themselves then the term 'mutation' without any qualification is fairly meaningless.As to the difference between new retroviral insertions and transposons, I agree that there is no functional difference on the genome between the two, the difference comes in terms of our ability to reconstruct the history of the genome and in terms of whether insertions were the result of jumping around within the genome or a novel insertion, as far as that relates to arguments on informational content of a genome, a line of argument I have never had the neccessary understanding of definitions of information to be really certain of following.This relates to something Mammuthus said in the HERV thread. TTFN,WKP.S. Thanks to mammuthus for that genomatix link, the Matinspector program itself wasn't much use but the Bibliosphere program is very interesting, considerably superior to the other literature mining programs I have tried.

Well, I second the vote for the resource Mammuthus recommended because I think it gives you the best flexibility in terms of setting your own parameters.

When you hear someone say 'mutation' what do you assume? I would argue that the term is already so broad that qualification is required if the specifics are known.I thought I'd check some definitions, in case I was loony: My interpretation is that 'any' would include HGT.I'm not trying to be unneccessarily argumentative here - it just seems that defining something as 'non-Mendelian' follows directly from how 'mutation' and 'inheritance' are defined.

My statements have not been inaccurate; to clarify: I never said Mendel "covered" environment in his laws, instead I said that gene-environment interactions do not violate his laws.Mendel's two laws, as I understand them:- independent segregation of alleles
- independent assortment of genesEnvironmental effects on the penetrance or expressivity of a phenotype do not violate these laws (since Mendel's laws do not "cover" phenotypes, arguments from phenotype cannot violate them, methinks...)You used the phrase "the role of environment on inheritance" - I assume you mean 'inheritance' of phenotype. If you have an example of the environment effecting segregation of alleles, or independent assortment of genes, then that might qualify as "non-Mendelian".

Hi WK,Just a thought or two about epigenetics, a concept I have only recently come across, but find quite intriguing (so no doubt you and Mammuthus can put me straight on a couple of things ).

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I was thinking along the lines of epigenetic effects such as DNA methylation, which is not only responsible for your imprinting but for other heritable changes, or heritable histone alterations of chromosome structure. Many of these epigenetic factors may not be heritable in the long term, at the moment it is not clear to what extent epigenetic factors are generally heritable or how stable those factors are.

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From the little reading I have done on the subject, it occurs to me that although the idea that epigentic factors can have a direct effect on phenotype is non-Mendalian (not to mention non-Darwinian) at first glance, the ability to produce offspring which could vary according to environmental changes could be a selectable trait in itself. In environments where there is a high amount of change it would be advantageous to be flexible in the kind of offspring you produce (very similar to the way that sex ratios change in reptiles and birds). On the other hand if a specific morphology (for example) was trumping all others then it would make sense to 'fix' it in place with a more permanent mutation. In a review I read a while back (which I now can't find ) it suggested that this variability followed by fixation could be a possible 'fast-track' to speciation.Any thoughts?

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P.S. Thanks to mammuthus for that genomatix link, the Matinspector program itself wasn't much use but the Bibliosphere program is very interesting, considerably superior to the other literature mining programs I have tried.

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I have not used Matinspector myself but a colleague of mine is scanning HERV LTRs for conserved transcription binding sites with great success. On the other hand, the regions he has to scan are a few kb and not 1.5 Mb. Bibliosphere is an interesting program though you have to play around with the filter or you end up with a lot of junk.

Imprinting is heritable. It is a non-DNA based heritable change. Whether a fast track to speciation or a potential species barrier is an interesting question. Slight changes in imprinting seem to account for the failure of clones to develop (and those that do have abnormalities) so it is also possible that differences in imprinting could prevent two closely related species from forming F1's even if their DNA sequences are very similar. I don't know how much this has been looked into. On the other hand, it is pseudo-mendelian. You inherit the imprint from your parents so would it contradict or merely supplement DNA vertical transmission?

Hi Ooook,There are really two distinct but related concepts of epigenetics being discussed here. Initially epigenetics was used to cover short term alterations to a cell lineage leading to differring cell phenotypes from genetically identical cells, many of the inputs for which are environmental. More recently the inheritance of epigenetically modified DNA, modifications not affecting the primary sequence of the DNA, has become a hot area of research.Both of these share common mechanisms for modifying the genome, such as methylation and chromatin remodelling.What you seem to be describing is a rather loose form of the 1st type, where you suggest that phenotypic plasticity is itself a desirable heritable trait. What you are describing seems to be rather a normal genetic system but one which allows for phenotypic plasticity followed by a restriction of that plasticity, say through the mutation of sites required for the expression of a no longer required phenotype.Clearly this relates to the developmental basis of phenotypic plasticity and therefore epigenetics in the sense of the environmental factors affecting development of the disparate phenotypes. It does not seem to be either a non-mendelian nor a non-darwinian mechanism in the way that the 2nd form of epigenetics may be considered to be.To me you seem to be discussing something along the lines of 'evolvability', I just came across a paper I read some time ago when I was first getting interesed in Evo-Devo, which Mammuthus mentioned previously, which discusses both 'evolvability' and the possible role of Evo-Devo as the source of a major updating of the modern synthesis. For an example of epigenetic inheritance I shall give the address of a full-text article on a heritable methylation based trait in mice. TTFN,WK