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Author Topic:   Definition of Species
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 348 of 450 (624500)
07-18-2011 10:05 AM
Reply to: Message 347 by Big_Al35
07-18-2011 7:01 AM


Frameshifts
I think I have been right all along in pressing for proper identification of a gene difference.
Care to explain why?
Frame-shift is when DNA across species, which may be very similar, (as in the case of humans and chimps) produces very different genes.
There is no need to bring species into this in terms of a definition, frame-shift mutations can produce mutations just as readily trans-generationally. Indeed there are probably many cells within your own body hosting frameshift mutations.
sequences of DNA which are almost identical will produce different proteins because the start and end points for reading the code are different. Maybe WK or one of the other biologists here could elaborate on this point.
When mRNA sequences are translated into protein sequences the correct amino acid for each step of the protein synthesis is determined by a 3 nucleotide long 'codon' after an amino acid has been incorporated the next 'codon' determines the subsequent amino acid in the protein synthesis. The way that a given sequence translates based on a particular start site is called its reading frame. Any stretch of nucleotides has 3 reading frames, but traditionally only 1 is thought to be functional (although some recent research disagrees).
Because of this arrangement insertion or deletion mutations that are not a multiple of 3 can cause frameshifts because all the codons downstream of such a mutation have had their reading frame altered, or shifted, by whatever size the insertion/deletion was. This means that a frameshift mutation can alter every single amino acid coded by the sequence that comes after the codon affected by the mutation.
This makes frameshifts one of the more radical forms of mutation at the level of genes. It is a simple one step change which can render a protein non-functional. It is also a mechanism which there is some evidence to support as a source of the de-novo generation of new genes, as in the Nylonase digesting enzymes (Ohno, 1984) or in a number of human genes (Knowles and McLysaght, 2009).
TTFN,
WK

This message is a reply to:
 Message 347 by Big_Al35, posted 07-18-2011 7:01 AM Big_Al35 has replied

Replies to this message:
 Message 350 by Big_Al35, posted 07-19-2011 6:15 AM Wounded King has replied
 Message 357 by Big_Al35, posted 07-21-2011 7:21 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 351 of 450 (624638)
07-19-2011 6:57 AM
Reply to: Message 349 by Taq
07-18-2011 5:12 PM


Re: Gene Deletion
I looked it up and the actual mutation in the human lineage is a 2 base deletion in exon 18 of the gene. This deletion introduces a stop codon about 30 bases further downstream. This results in the protein being truncated from its expected size of 223 kilodaltons down to 76 kilodaltons.
Interestingly the gene is still transcriptionally active in a tissue specific fashion, being expressed in the jaw muscles as it is in other primates.
TTFN,
WK

This message is a reply to:
 Message 349 by Taq, posted 07-18-2011 5:12 PM Taq has not replied

Replies to this message:
 Message 359 by Big_Al35, posted 07-21-2011 8:05 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 352 of 450 (624640)
07-19-2011 8:03 AM
Reply to: Message 350 by Big_Al35
07-19-2011 6:15 AM


Re: Frameshifts
If you know of any beneficial mutations that would be intriguing.
Do you mean a modern contemporary spontaneous beneficial frameshift mutation in the human population?
TTFN,
WK

This message is a reply to:
 Message 350 by Big_Al35, posted 07-19-2011 6:15 AM Big_Al35 has replied

Replies to this message:
 Message 355 by Big_Al35, posted 07-21-2011 5:33 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 354 of 450 (624803)
07-20-2011 5:03 AM
Reply to: Message 353 by Taq
07-19-2011 8:45 PM


Re: Frameshifts
Except the one that allowed for one of the most important evolutionary changes in the hominid lineage, the MYH frameshift mutation that allowed for the expansion of the brain.
To be fair that is pretty much speculation. The fact that the mutation's origin coincided with the expansion of the brain, give or take a few million years is far from conclusive as to a causative relationship.
Other researchers have suggested that in fact the mutation occurred much closer to the original chimp-human lineage split (Perry et al, 2005) rather than alongside the appearance of Homo in the fossil record as Stedman et al. (2004) suggested.
McCollum et al (2006) wrote a review bringing forward several lines of evidence calling into question Stedman's hypothesis as to the significance of MYH16. These included the timing of the mutation, the known effects of jaw musculature on constraining brain development and the fact that the majority of brain development occurs well before such muscles are well established and developed to their full force generating potential.
TTFN,
WK

This message is a reply to:
 Message 353 by Taq, posted 07-19-2011 8:45 PM Taq has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 356 of 450 (625014)
07-21-2011 7:03 AM
Reply to: Message 355 by Big_Al35
07-21-2011 5:33 AM


Re: Frameshifts
Only from this context can we then move on to presuppose frameshifting across the species.
Why on earth do you think this?
Any other ludicrous and irrelevant stipulations you want to make? Can we only consider macroevolution if the moon is made of green cheese?
Contemporary beneficial mutations of any kind in human populations are incredibly hard to detect. Unlike deleterious mutations with obvious major phenotypes, such as Tay-Sachs, no one is brought into hospital as the result of beneficial mutation.
We can only detect beneficial mutations through exhaustive longitudinal studies over generations and capturing the initial generation of one de novo and then following it would be almost impossible.
There are some plausible already extant candidates however. One example would be the CCR5 delta-32 isoform. This is a frameshifted version of the CCR5 gene which has undergone a 32bp deletion and produces a severely truncated protein. This mutation appears to confer a degree of protection from HIV-1 (Trecarichi et al. 2006). Some researchers have suggested that the prevalence of this mutation is simply consistent with neutral evolution (Sabeti et al., 2005) but a more recent review (Oleksyk et al., 2010) outlines a number of flaws with this position. Either way the origin of this mutation is probably between 1000 to 5000 years ago so whatever selective pressure it was susceptible to it is unlikely to have been HIV-1 infection. Whether it will now be a target of selection due to HIV-1 is an open question which only future transgenerational studies will reveal.
TTFN,
WK

This message is a reply to:
 Message 355 by Big_Al35, posted 07-21-2011 5:33 AM Big_Al35 has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 361 of 450 (625039)
07-21-2011 8:32 AM
Reply to: Message 357 by Big_Al35
07-21-2011 7:21 AM


Re: Frameshifts
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,
WK
Edited by Wounded King, : Added reference to Evans et al.

This message is a reply to:
 Message 357 by Big_Al35, posted 07-21-2011 7:21 AM Big_Al35 has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


(1)
Message 362 of 450 (625042)
07-21-2011 8:39 AM
Reply to: Message 359 by Big_Al35
07-21-2011 8:05 AM


Re: Gene Deletion
So far from it actually pushing the stop codon further downstream as we had previously implied
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

This message is a reply to:
 Message 359 by Big_Al35, posted 07-21-2011 8:05 AM Big_Al35 has replied

Replies to this message:
 Message 365 by Big_Al35, posted 07-21-2011 9:59 AM Wounded King has replied
 Message 371 by Big_Al35, posted 07-21-2011 11:26 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


(1)
Message 363 of 450 (625044)
07-21-2011 8:42 AM
Reply to: Message 360 by Big_Al35
07-21-2011 8:12 AM


Re: Frameshifts
One minute WK suggests that frameshifting is likely to be evident even in my own body and the next he says that there is no chance of getting any hard evidence to prove this point.
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

This message is a reply to:
 Message 360 by Big_Al35, posted 07-21-2011 8:12 AM Big_Al35 has replied

Replies to this message:
 Message 364 by Big_Al35, posted 07-21-2011 9:57 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 366 of 450 (625077)
07-21-2011 10:20 AM
Reply to: Message 364 by Big_Al35
07-21-2011 9:57 AM


Re: Frameshifts
Huh! I am still waiting for a human to human beneficial frameshift mutation as we previously discussed.
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,
WK
Edited by Wounded King, : Added link to previous post

This message is a reply to:
 Message 364 by Big_Al35, posted 07-21-2011 9:57 AM Big_Al35 has replied

Replies to this message:
 Message 369 by Big_Al35, posted 07-21-2011 10:35 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 367 of 450 (625078)
07-21-2011 10:23 AM
Reply to: Message 365 by Big_Al35
07-21-2011 9:59 AM


Re: Gene Deletion
How is it plagiarism when I've given you the link?
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

This message is a reply to:
 Message 365 by Big_Al35, posted 07-21-2011 9:59 AM Big_Al35 has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 370 of 450 (625096)
07-21-2011 11:07 AM
Reply to: Message 369 by Big_Al35
07-21-2011 10:35 AM


Re: Frameshifts
Ok, you finally admit that 'I got you'.
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

This message is a reply to:
 Message 369 by Big_Al35, posted 07-21-2011 10:35 AM Big_Al35 has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 372 of 450 (625120)
07-21-2011 1:37 PM
Reply to: Message 371 by Big_Al35
07-21-2011 11:26 AM


Re: Gene Deletion
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.
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.
I suggest this because it strikes me that a frameshift is more likely to result in a spontaneous stop codon generation later in the DNA sequence rather than earlier. It's simple statistics and probability.
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

This message is a reply to:
 Message 371 by Big_Al35, posted 07-21-2011 11:26 AM Big_Al35 has not replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 374 of 450 (625319)
07-22-2011 9:54 AM
Reply to: Message 373 by Big_Al35
07-22-2011 7:00 AM


No pesudogenisation? Are you sure?
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,
WK
Edited by Wounded King, : No reason given.

This message is a reply to:
 Message 373 by Big_Al35, posted 07-22-2011 7:00 AM Big_Al35 has replied

Replies to this message:
 Message 377 by Big_Al35, posted 07-23-2011 6:31 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 378 of 450 (625493)
07-23-2011 1:09 PM
Reply to: Message 377 by Big_Al35
07-23-2011 6:31 AM


Re: No pesudogenisation? Are you sure?
It begs the question of how a frameshift like this could occur in such a highly conserved area.
Again the question isn't really how such a mutation can occur, that is a simple result of random mutations, but rather why this particular frameshift has subsequently become fixed in the human population.
Yes, I am just running through the list of genes that were provided earlier.
Well apparently you didn't bother reading the source material the list came from, or indeed even paying close attention to the original post with the list in, if you had then you would already have seen that SIGLEC-13 wasn't completely deleted but rather a pseudogene.
Your link doesn't really seem to provide any evidence at all supporting a deletion, so I suppose the contributor who made the entry may just have made a mistake.
TTFN,
WK
Edited by Wounded King, : No reason given.
Edited by Wounded King, : No reason given.

This message is a reply to:
 Message 377 by Big_Al35, posted 07-23-2011 6:31 AM Big_Al35 has replied

Replies to this message:
 Message 380 by IamJoseph, posted 07-23-2011 9:29 PM Wounded King has replied
 Message 382 by Big_Al35, posted 07-24-2011 6:37 AM Wounded King has not replied
 Message 383 by Big_Al35, posted 07-24-2011 6:52 AM Wounded King has replied

  
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 381 of 450 (625574)
07-24-2011 4:54 AM
Reply to: Message 380 by IamJoseph
07-23-2011 9:29 PM


Re: No pesudogenisation? Are you sure?
If its random then the result is not predictable, and a zebra will not necessarilly reproduce a zebra.
Well sometimes a zebra doesn't produce a zebra in the same way that many human pregnancies end in spontaneous abortions very early in the embryo's development. A number of these can be ascribed to embryonic lethal mutations which severly disrupt the embryo's development to the point of making it unviable.
But no one is suggesting that an organisms entire genetic complement is randomised every generation. You seem to have come up with a new insane creationist strawman, well done.
As it turns out it is not random and a life form follows its own kind, solely dependent on the program directive transmitted via the seed output of the host
If by seed output you mean germ cells, i.e sperm and egg, then you are wrong. How an organism develops is not solely dependent on this. It also depends on a wide variety of environmental factors.
Going by your reasoning every single organism should be an exact 50%/50% mixture of its parents' DNA, but we know this isn't the case from multiple studies across a wide variety of organisms. Even within an organism's somatic tissues many novel mutations can be identified.
Mutations occur, some are harboured in the germ cells and some occur during the development of the embryo and can be passed on in that organism's own germ cells some occur in somatic tissues that will never contribute to germ cells.
Clearly the germ cells are needed as the medium to convey genetic material in sexual species but that doesn' t say anything about mutation being random or not.
So could you try and make coherent argument this time?
TTFN,
WK
Edited by Wounded King, : No reason given.

This message is a reply to:
 Message 380 by IamJoseph, posted 07-23-2011 9:29 PM IamJoseph has replied

Replies to this message:
 Message 384 by IamJoseph, posted 07-24-2011 7:24 AM Wounded King has replied

  
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