Summations Only

So you can't tell the difference between a mutation and a beneficial mutation, duly noted. I guess we just add it to the long list of things you don't know what you are talking about.I mean I assumed you since you yourself had already brought up a specific human frameshift mutation, in terms of Tay-Sachs, that you accepted the existence of frameshift mutations.But if you want to totally change the topic and just discuss the very existence of frameshift mutations in humans then fine, it would help if you signified these shifts in topic a bit though. It would be especially helpful if you didn't specifically agree with me to discuss one thing, Message 355, and then pretend we had been talking about something else.The existence of somatic frameshift mutations is everywhere in the biomedical literature, especially in research related to cancer for a sample here is a link to a pubmed search using the terms 'Human Somatic Frameshift'.The mutation rate for frameshift mutations in normal somatic cells is not well characterised but given that there are some several trillion cells in the human body and many of those are in a constant state of turnover I can't really see how you could fail to have had at least 1 frameshift mutation in there somewhere, one calculated somatic mutation rate is 3.4 10−7 mutations per cell division (Araten et al., 2005). There is also some research strongly suggesting that most humans harbor frameshifted forms of the Vasopressin gene in certain neural cells and that many other genes may be similarly affected (Evans et al., 1996)TTFN,WKEdited by Wounded King, : Added reference to Evans et al.

I don't know when anyone implied this. As far as I can tell you just reiterated what I was saying but took out most of the technical detail. In fact it looks like you cut and pasted some text from your link and didn't bother to tell us you were plagiarising.The '30bp further downstream' that you quote from me is in relation to the site of mutation. There is a 2bp deletion and this causes the codon which starts 30bp further downstream from the mutation site to become a stop codon.So far from you bothering to understand what I wrote you just reiterated it by cutting and pasting from a blog describing the same research as I had already linked to and made out as if it somehow contradicted what I was saying.TTFN,WK

Reading comprehension FAIL as explained above. You agreed we were talking about "a modern contemporary spontaneous beneficial frameshift mutation in the human population" and then changed it into just being any somatic frameshift.TTFN,WK

Huh! I am still waiting for a human to human beneficial frameshift mutation as we previously discussed. All the examples so far relate to the negative impact of a frameshift event. Your last example and links relate to frameshifts which result in cancer tumours. Hardly a beneficial mutation!Anyway, I am still waiting but I won't hold my breath.

How is it plagiarism when I've given you the link?

Presumably by "Huh!", you mean 'OK you got me, I was shifting the goalposts, but rather than admit that I'm going to ignore it, pretend I was also talking about something else and go back to demanding yet more evidence which I will also promptly ignore'.Why not go back and read the post in which I told you why finding such mutations would be incredibly challenging, Message 356. And then maybe you could tell us why it is in the slightest bit relevant to the actual topic of this thread.TTFN,WKEdited by Wounded King, : Added link to previous post

Because you in no way indicated that the whole 2 sentences which contained that link were in fact directly lifted from it. Now instead of blustering care to try and explain why you posted something that just re-iterated what I had already described?TTFN,WK

By not putting it in a quote box you presented it as your interpretation of the information in the link.You can rationalize all you want but what you did was plagiarizing. Quote boxes are very easy to use. There is no excuse not to use them when you cut and paste something.

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Facts don't lie or have an agenda. Facts are just facts

Ok, you finally admit that 'I got you'. Why the pulava over this minor point any how. I am simply trying to progress this discussion in a meaningful way.I am pretty sure that if I had made a random claim without backing it up with evidence you guys would have been very quick to slam me for it. Hence I tend to ask for evidence before progressing to the next point. If you had just been open and forthright about your spurious claim we could have skipped over it and moved onto a discussion which might be more meaningful to yourself.Edited by Big_Al35, : No reason given.

Please re-read and try to understand the previous exchange, I'd suggest starting at Message 348.The only thing you have 'got' is a fundamental inability to comprehend.Are there cells containing novel frameshift mutations in your body, almost certainly. This is what I previously claimed and I have also provided evidence for.Are they beneficial? Probably not, but this is not something that I have ever claimed. They certainly aren't likely to be beneficial mutations that will be passed on because they are somatic.So why not tell us exactly what the spurious claim was that you think I made? Ideally with an actual quote from me which is relevant.TTFN,WK

Actually, this raises another point about which is the mutant strain. MYH16 in humans is classed as the defective frameshifted version whereas it seems just as likely that the chimp version is the effective frameshifted version. The 2bp deletion could equally be considered a 2bp addition. Chimps and humans after all are both modern species and it could be that the human version is the original but became a rather successful alternate allele in other primates. I suggest this because it strikes me that a frameshift is more likely to result in a spontaneous stop codon later in the DNA sequence rather than earlier. It's simple statistics and probability.Edited by Big_Al35, : No reason given.

The genetic evidence from other species contradicts this as indeed does the phylogenetics of the primates. For the human state to be ancestral would require the 2bp insertion you hypothesise to have ocurred independently in multiple lineages unless we just ignore the patterns of conservation from almost the entire rest of the genome and reroot the phylogenetic tree with humans being the earliest branching lineage. Care to provide any sort of rationale based on statistics and probability to actually support this claim rather than just leaving it as a baseless assertion?I'm not saying that what you say may not be true, but I think it is worth more explanation than simply saying "statistics and probability". Obviously the closer to the initial start codon a frameshift mutation occurs the more chance it has of affecting the whole downstream sequence and the earlier in the sequence a premature stop can arise. I'd certainly agree that as you move further from the initial mutation site the chance of a stop having occured at some point within the frameshifted gene already increases. And obviously if the initial mutation occurs later in the sequence any resultant stop would also be later. This is highly dependent on the specific nature of the sequence involved however, some frameshifts will remove stops and can even result in the generation of fused proteins.I fail to see how this phenomenon would in any way tie in to your speculation that the truncated form represents the ancestral state of the gene.TTFN,WK

On a separate point the gene SIGLEC-13 has been completely deleted from the human genome but appears amongst the other great apes. No pseudogenization, frameshift or point mutation here just a complete deletion. Maybe one of the biologists can explain how selective forces might apply to eradicate all traces of a gene?

It depends, exactly what you actually want to ask. Deletions of substantial genetic stretches are not uncommon and may easily encompass a whole gene coding region. But that is an issue of mutation and not of selection.So are you asking why natural selection would favour or at least not select against deletions of this specific gene? Without a better understanding of exactly what the loss of any particular gene means functionally I'd simply be making up 'Just So' stories.Looking at the genome sequences however I'm not convinced that the Siglec13 gene is as thoroughly deleted as you suggest. If you go to the Evolutionarily Conserved Regions (ECR) browser, here, you will find a multispecies alignment around the Siglec13 region. You will need to add the human sequences into the alignment by clicking on the little blue plus sign above the icons of the various animals. From this alignment it looks like there is still substantial conservation across the Siglec13 locus, it certainly isn't consistent with a wholesale deletion.So what is your source for the complete deletion of Siglec13 in humans? Perhaps they merely meant that the gene had been rendered non-functional. In fact something rang a bell here and looking back I see that Siglec13 was actually referenced in one of the papers I cited earlier as a human specific pseudogene, see Message 303.TTFN,WKEdited by Wounded King, : No reason given.

Hello everyone!I'm going to recuse myself from discussion as Percy for a couple days, then beginning Monday morning I will take on a moderator role as Admin. I'll be looking for continuity in discussion, where lack of continuity is defined as lines of inquiry being suddenly initiated and equally suddenly abandoned. I'll also be making sure that discussion isn't wondering aimlessly but is focused on identifiable goals.

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--	Percy
	EvC Forum Director