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Author Topic:   Genetics and Human Brain Evolution
Wounded King
Member
Posts: 4149
From: Cincinnati, Ohio, USA
Joined: 04-09-2003


Message 89 of 157 (360199)
10-31-2006 5:27 PM
Reply to: Message 79 by eggasai
10-31-2006 12:41 PM


A little exercise for thy cerebellum's sake.
I know Sfs has already addressed a lot of this so please forgive any duplications of the covered material.
I know what the problem is, you don't know what a reading frame is.
I'm not sure why you think open reading frames are particularly important in this instance, but rest assured I know what one is.
a gross stuctural change is nothing more then 20% of the protein coding genes are much more different then predicted.
This is not the case. The 'gross structural change' refers to the actual change to the sequence. My point against this was that not all of the 'gross structural changes' were indels as you contended, your point seems to have been that you don't know what the hell you are talking about.
From the paper...
47 PTR22q genes show significant structural changes affecting at least one of their transcript isoforms.
So there are significant structural changes within the genes affecting their products. These are the gross structural changes in 20.3% of the genes. It is not that 20.3% being unexpectedly divergent is in itself a gross structural change, of these gross structural changes only 15 are indels.
You don't realize that the regulatory genes come in amino acid sequences do you?
There are lots of different types of regulatory gene, the vast majority with which we are familiar are indeed protein coding but there is a rapidly growing body of evidence to show that there are several other forms of genetic regulation which are mediated by non-coding RNA transcripts, one such form are microRNAs such as have been just detailed in terms of the differences betwen chimps and human with regard to the brain (Berezikov et al., 2006).
Now as far as mutations that involve in hundreds of millions of base pairs or nucleotides then I want to see it.
Reading comprehension really isn't your strong suit is it, what I said was 'hundreds to millions' and you yourself pointed out at least one 4Mb chromosome rearrangement.
Oh really? Here is a list of known effects from mutations that involve genes in the human neural system
Which is exactly what I predicted you would produce ad far back as the first page, and as I pointed out then the existence of some deleteious mutations with phenotypic effects significant enough to be readily apparent in no way means that all mutations will be detrimentla, I see that you have even backpedalled a bit and are now only saying that mutations would be detrimental most of the time. The seems to be an equally unevidenced assertion but a considerable improvement since it at least allows for some mutation, not every single one being lethal as you previously claimed.
I'd now like to revisit Har1. Lets forget about the paper for a moment and look at the data.
This link will take you to the entrez nucleotide page for the Har1 sequences from the paper we were discussing. You will note that both sequences are identified as 'non-protein-coding RNA'.
If we click on the second sequence there Har1A then you will be taken to the sequence of the highly accelerated region.
If you scroll down to just before the actual sequence starts you will find a 'misc feature' annotation link which is the actual 'highly conserved' 118bp sequence.
If you copy that sequence and put it into Entrez's ORF finder program it won't find a single one. If you take the whole Har1 region and put it through ORF finder you will see a number of possible ORF's and the nucleotide ranges they span, none of these ORFs span the region from 851-968 within which the highly conserved region is found.
If there is a mistake here then please show me where it is, if not then please finally admit that this sequence does not functionally code for any protein sequence whatsoever!!
This exercise shouldn't take more than a couple of minutes at most so please go through it and tell me what you are seeing that neither I, the ORF-finder program nor the authors of the original paper can see.
TTFN,
WK
Edited by Wounded King, : No reason given.

This message is a reply to:
 Message 79 by eggasai, posted 10-31-2006 12:41 PM eggasai has not replied

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


Message 91 of 157 (360222)
10-31-2006 6:22 PM
Reply to: Message 90 by eggasai
10-31-2006 5:29 PM


Wilful ignorance
Then I am informed by unanimous consent of scientific professionals I don't have a clue about the basics.
And from this you conclude that everyone is prejudiced against you because you are a creationist? Is there no other conceivable reason that coms to your mind? No, I guess not.
TTFN,
WK
Edited by Wounded King, : because I forgot, 'i before e except after c where the sound is /i:/'

This message is a reply to:
 Message 90 by eggasai, posted 10-31-2006 5:29 PM eggasai has replied

Replies to this message:
 Message 96 by eggasai, posted 11-01-2006 9:32 PM Wounded King has not replied

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


Message 94 of 157 (360365)
11-01-2006 9:19 AM
Reply to: Message 88 by sfs
10-31-2006 3:51 PM


Now see what you've done!!!
Naughty sfs!!
Barging in here, without as much as a 'by your leave', and scaring off our creationists.
You're hardly ever in, you don't call to let us know where you are but you turn up like the proverbial bad penny to frighten the latest squeaky rubber creationist bit substitute, for our champing horse like teeth, back into the undergrowth.
I am most cross with you.
TTFN,
WK
Edited by Wounded King, : Basically because I have the typing aptitude of an untrained monkey

This message is a reply to:
 Message 88 by sfs, posted 10-31-2006 3:51 PM sfs has replied

Replies to this message:
 Message 98 by eggasai, posted 11-01-2006 10:11 PM Wounded King has replied
 Message 121 by sfs, posted 11-02-2006 11:10 PM Wounded King has not replied

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


Message 100 of 157 (360629)
11-02-2006 2:21 AM
Reply to: Message 98 by eggasai
11-01-2006 10:11 PM


Re: Now see what you've done!!!
Disingenuise double talk and the semantical slight of hand you guys are using disgusts me.
Fine then lets do away with semantics and look at some raw data, I'll repost the exercise I suggested earlier.
This link will take you to the entrez nucleotide page for the Har1 sequences from the paper we were discussing. You will note that both sequences are identified as 'non-protein-coding RNA'.
If we click on the second sequence there Har1A then you will be taken to the sequence of the highly accelerated region.
If you scroll down to just before the actual sequence starts you will find a 'misc feature' annotation link which is the actual 'highly conserved' 118bp sequence.
If you copy that sequence and put it into Entrez's ORF finder program it won't find a single one. If you take the whole Har1 region and put it through ORF finder you will see a number of possible ORF's and the nucleotide ranges they span, none of these ORFs span the region from 851-968 within which the highly conserved region is found.
If there is a mistake here then please show me where it is, if not then please finally admit that this sequence does not functionally code for any protein sequence whatsoever!!
This exercise shouldn't take more than a couple of minutes at most so please go through it and tell me what you are seeing that neither I, the ORF-finder program nor the authors of the original paper can see.
No semantics here, just a chance for you to analyse the raw data yourself and come to a conclusion.
TTFN,
WK

This message is a reply to:
 Message 98 by eggasai, posted 11-01-2006 10:11 PM eggasai has replied

Replies to this message:
 Message 103 by eggasai, posted 11-02-2006 6:43 AM Wounded King has replied

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


Message 101 of 157 (360633)
11-02-2006 2:45 AM
Reply to: Message 98 by eggasai
11-01-2006 10:11 PM


Cross-purposes
He gives this formula and enters bp in the equation, it seems pretty obvious that it stands for base pair. Then he says it's not base pairs it's the single base substitution rate. No matter how many times I measure divergence by base pairs I will be wrong because bp is not base pairs even though that is how he has been using it for almost a year.
The rate is mutations per length of genome per period of time.
2x10^-8 mutations per base pair of length per generation. So if those mutations, as the indels do, affect more than 1bp (18-300bp average, doesn't matter which really) at a time then using that mutation rate figure to calculate the actual basepair divergence will not work.
The second point was that that was not actually an accurate measure of the mutation rate overall but of the mutation rate for single base substitutions specifically. This means that were there only single base substitutions occurring then you would be able to use the formula as you wish to, but since we know there are indels, inversions and other mutations which affect more than 1bp at a time such an approach will not give you an accurate figure.
You can measure the divergence in bp as much as you want, but using that figure alone coupled with a single nucleotide substitution based mutation rate which fails to take into account substantial indels will give you an inflated needed rate of mutation. Most of the time for a single protein coding gene this approach would be fine, but over the whole genome where there are such large scale muations evident it would be innaccurate.
Here is an example:
Sequence: atgtgggttagtgcgcgttgaaggccgtgattagcgcgcgcgtatgatc
Mutant 1: atgcgagttagtgcgcgttgaaggttgtgattagcgcgtacgtatgatc
Mutant 2: atgtgggttagtgcgcgttgaaaaaaaaaaaaaaaaaaaaaaggccgtgattagcgcgcgcgtatgatc
Mutant 1 has 6 single nucleotide substitions, mutant 2 has a single insertion of 20 nucleotides. Using the method you have been proposing that single insertion would require an increase in the neccessary mutations fixed or mutations per generation even though it is only a single mutation compared to the 6 in mutant 1.
Given the highly variable nature of the size of indels all you could really hope to produce is a more accurate rate of mutation, regardless of type, but this will never tell you how many bps are being changed per bp of premutational genome length. All you can tell is how many mutations would be needed and the rate that they would need to be fixed.
TTFN,
WK
TTFN,
WK

This message is a reply to:
 Message 98 by eggasai, posted 11-01-2006 10:11 PM eggasai has not replied

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


Message 104 of 157 (360679)
11-02-2006 7:09 AM
Reply to: Message 103 by eggasai
11-02-2006 6:43 AM


Re: Theater of the mind
I was willing to pursue this at any length.
Except the length of actually looking at any of the relevant basic molecular biology links which would reveal just how twisted your idea of molecular biology is?
Even now you won't look to see if, as I have repeatedly contended, there are regulatory genes which do not operate functionally as proteins. I'm not sure how you can hope to cover the basic life sciences when you have such a tenuous grasp on the fundamentals.
TTFN,
WK

This message is a reply to:
 Message 103 by eggasai, posted 11-02-2006 6:43 AM eggasai has replied

Replies to this message:
 Message 105 by eggasai, posted 11-02-2006 8:19 AM Wounded King has replied

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


Message 106 of 157 (360714)
11-02-2006 9:00 AM
Reply to: Message 105 by eggasai
11-02-2006 8:19 AM


Re: The truth will prevail, get on the winning side
That's just it, I don't have a tenuous grip of the basics, it never occured to me that RNA programed proteins.
Eh? What happened to DNA ---> RNA ----> protein? What do you mean here? A complementary mRNA strand codes for a protein just as much as, if not more then, the protein coding DNA strand from which it is transcribed. Not all RNAs are translated into protein but the vast majority from identified genes are. So what does 'RNA programed proteins' mean?
Just admit it, bp means base pair
I never denied it, in fact I said it just a post or two back when I was explaining what Sfs' formula actually meant, I think you would be hard pressed to find anywhere where Sfs has denied this either.
and mutations are measured in base pairs or single nucleotides.
Well I'm not sure I can agree to this. Certainly the length of an insertion or deletion or inversion would be measured in base pairs and so would the size of a region affected by a higher order chromosomal rearrangement. In terms of a mutation rate what one measures is the number of mutational events, this can be categorised based on the type of event to produce distinct mutational rates but an overall mutation rate will be in terms of the number of mutational events rather than the number of base pairs affected by the event. The size of a mutation is measured in bps not the number of mutations.
TTFN,
WK
Edited by Wounded King, : No reason given.

This message is a reply to:
 Message 105 by eggasai, posted 11-02-2006 8:19 AM eggasai has replied

Replies to this message:
 Message 108 by eggasai, posted 11-02-2006 5:41 PM Wounded King has not replied

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


Message 111 of 157 (360923)
11-02-2006 6:55 PM
Reply to: Message 110 by Hyroglyphx
11-02-2006 6:40 PM


Theater of the absurd
I don't why you were expecting honesty from a group that has no moral fiber to begin with and no real concept of morality apart from some relativistic, abstract concept.
Is this on topic? Do you have anything to add? If you want to contribute here why don't you try and help your rut stuck co-religionist to understand either the very basic fundamentals of molecular genetics which they seem incapable of grasping, I assure you it probably wouldn't take you more than 5 minutes of reading to see that Eggasai's conception is majorly messed up, or even the fundamentals of reading a formula which also seems to be causing them a lot of trouble.
Don't come here bemoaning hom immoral/amoral and dishonest we all are and commisserating with an ignorant, arrogant, virtual troll who can't be bothered to poke their head out of the shell of bullshit they have surrounded themselves with for long enough to see that in fact they don't know shit from shinola.
Do you have any idea who has the right side scientifically in this argument? If you agree with Eggasai why not provide some evidence if not then why are you accusing the rest of us of dishonesty?
If this an example of your honesty and moral fiber you are welcome to it.
TTFN,
WK
Edited by Wounded King, : No reason given.

This message is a reply to:
 Message 110 by Hyroglyphx, posted 11-02-2006 6:40 PM Hyroglyphx has replied

Replies to this message:
 Message 125 by Hyroglyphx, posted 11-03-2006 9:53 AM Wounded King has not replied

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


Message 124 of 157 (361055)
11-03-2006 7:17 AM
Reply to: Message 122 by eggasai
11-02-2006 11:49 PM


Re: Remedial reading for egg
The formula is 2 x 10^-8/bp/generation. You are telling me that bp means mutation events, not a count of base pairs. It is altogether untrue and an obvious contradiction.
Oh for Pete's sake, how many times!!
I think Sfs was wrong to give you credit for correctly representing the formula.
It is actually 0.00000002 mutations per base pair per generation.
By associating the x10^-8 with the subsequent bp you seem to be eliding over the '/'. Your formulation would be
'2 mutations / 1x10^-8 bp / 1 generation'
This will give you the same rate but in neither case are the mutations measured in bps nor are bps treated as equivalent to mutations.
The only way your interpretation would make any sense would be if the formula was '2x10^-8 bp/generation', which no one has ever suggested as a formula.
Can you actually show anything, other than this formula which totally fails to support your contention, which suggests that Sfs or anybody else other than you is trying to say bp means anything other than base pairs? The worst you could accuse Sfs of doing is assuming that when discussing the mutaation rate you would understand the unit to be mutations and therefore not explicitly specifying '2x10^-8 mutations/bp/generation'.
TTFN,
WK

This message is a reply to:
 Message 122 by eggasai, posted 11-02-2006 11:49 PM eggasai has replied

Replies to this message:
 Message 129 by eggasai, posted 11-03-2006 1:00 PM Wounded King has replied

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


Message 132 of 157 (361132)
11-03-2006 1:19 PM
Reply to: Message 129 by eggasai
11-03-2006 1:00 PM


Re: Remedial reading for egg
He says, '2 x 10^-8/bp/generation is the number of mutation events, not the number of base pairs. He says that straight up and flat out and you act as if it is either the gospel truth or it just doesn't matter that bp in this formula simply means base pair.
What the hell are you trying to say?
Do you know what 'per' actually means, you seemed to only a few posts ago but in this particular context you seem selectively blind.
For every 1 bp in a genetic sequence there is a mutational rate of 2x10^-8 mutations every generation. The base pair is one of the metrics against which the frequency of mutation is being measured the other is the time in generations.
The bp can means base pair but it doesn't measure base pairs.
Sure it can when you are measuring the length of a sequence, it even could be used as a measure of the number of mutations if you were talking about a homogenous set of mutations of a fixed length, but when you are discussing a mutation rate for a heterogenous set of mutations varying in length from 1bp to >300bp then base pairs is not a unit which will be useful to measure how many mutations occurred.
If I tell you how long a sequence of DNA was prior to and subsequent to mutation could you tell me how many mutations had occurred? Could you tell me if I told you what number of bps were divergent?
TTFN,
WK

This message is a reply to:
 Message 129 by eggasai, posted 11-03-2006 1:00 PM eggasai has replied

Replies to this message:
 Message 138 by eggasai, posted 11-04-2006 9:03 PM Wounded King has replied

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


Message 141 of 157 (361789)
11-05-2006 6:13 AM
Reply to: Message 138 by eggasai
11-04-2006 9:03 PM


Re: Remedial reading for egg
I was saying is that bp in the formula meant base pair.
Bull! No one has ever denied that. What you have repeatedly said in multiple posts is that SFS was denying that this was what bp menat, which he has never done!!
msg 90 writes:
quote:
2x10^-8/bp/generation,is the number of mutation events, not the number of base pairs
Then what does bp stand for in your formula if not base pairs?
This seems to be thefirst instance of your issue and Sfs has already answered it, the bp is base pairs but the mutation rate isn't measured in base pairs. If he had said 'bp is the number of mutation events not the number of base pairs', then you might have a leg to stand on, but he never did and neither did anyone else.
It is you that wishes to make a meal out of these piddling little things. I'd much rather get back to your complete misunderstanding of fundamental molecular biology or to your non-existent references for seminal papers from Watson and Crick.
Better still we could get back to discussing Har1 and the evolution of the human brain or to the paper I referenced on non-coding mRNAs with a possible role in neural development due to expression differences between chimp and human brains.
Then you want me to assume that bp does not mean base pair.
Give us any example of anyone saying any such thing!!
The only person who has ever said anything suggesting anyone believes this is you!
You keep saying that mutations should be measured in bps but this only make sense in terms of measuring the length of a mutation not its frequency. If someone derived a reliable average for the number of bases affected per mutation then you could use the number of bps of difference as a metric for the frequency of mutation, but the 2x10^-8 figure was not derived in any such way and conseqently can't be used in that way. So, no matter how often you claim it, in the absence of such an average length value for all mutations bps are not a suitable measure for the number of mutational events.
If you think the mutation rate we are discussing does include such an averaging of the length of mutations then please provide a source reference that we can use to verify it. I have referenced at least 2 papers producing similar estimates neither of which account for any indels over 4bp in length.
Time magazine lied about the divergance, Nature lied about the divergance and you guys are twisting a very simple math problem into an incomprehesible gibberish.
Get over it already. Time and the people who produce the press releases at Nature are not exactly the cutting edge of evolutionary research. If you want to show that people are still frequently misquoting the divergence in science then why not refer us to some scientific papers? If you want to argue that science is poorly understood in the media and much of science reporting is badly done I doubt you will get much argument.
Two, if someone comes along and realizes that it is actually 95% immediatly act as it it made no difference that 100,000,000 base pairs doesn't change anything.
Of coure it changed things but it didn't change estimates of single nucleotide substitution rates and it didn't change historical estimates of the overall divergence derived using less accurate techniques. Did it make it impossible for chimps and humans to have a common ancestor 7 million years ago? No.
TTFN,
WK

This message is a reply to:
 Message 138 by eggasai, posted 11-04-2006 9:03 PM eggasai has not replied

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


Message 146 of 157 (362558)
11-08-2006 4:53 AM
Reply to: Message 145 by Dr Adequate
11-07-2006 11:09 PM


Re: bp does not mean base pair no matter what
Wounded King did not say that. You made that up.
He was actually talking about something Sfs said, but what Sfs said wasn't 'bp does not mean base pairs' either.
TTFN,
WK

This message is a reply to:
 Message 145 by Dr Adequate, posted 11-07-2006 11:09 PM Dr Adequate has not replied

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


Message 147 of 157 (362624)
11-08-2006 11:41 AM
Reply to: Message 144 by eggasai
11-07-2006 7:21 PM


Re: bp does not mean base pair no matter what
Could you finally once and for all give us a source for your mutation rate? I have mentioned a number of papers which have similar values derived principally from single nucleotide substitutions. The mutation rate for indels is estimated to be ~10 fold less than that for single nucleotide substitutions (Nachman and Crowell, 2000) where the rate of single nucleotide substitutions is measured as 2.3X10-8 substitutions/bp/generation and that for length mutations as 2.3X10-9 indels/bp/generation, giving an overall mutation rate of 2.5X10-8 mutations/bp/generation.
Assuming your 2X10-8/bp/generation figure has a basis in similar numbers we should expect something slightly under 10% of mutations to be length mutations so of your 120-175 or however many mutations there are per generation we might expect ~10-15 of those to be length mutations of anywhere between 1bp up to several Kb. The average length of an indel has been calculated at 36bp (Britten et al, 2003) and the median length to be 3bp (Ogurtsov et al., 2003). Most such length mutations will therefore be on the lower end of the scale but there should be enough longer ones to make an assumption that there is a tenable one to one mapping between the number of mutations and the amount of difference in bps highly suspect. Indeed if we take the average length of indel 36bp and use it to calculate the amount of divergence in bp we might expect to see with an indel mutation rate of 2.3X10-9 indels/bp/generation we get a figure, 8.2X10-8 bp of difference/bp/generation, which is actually more than 3 times as high as the amount of bp change we would expect from the single nucleotide substitution rate. The average is a daft figure to use of course, the median is probably much more realistic but is still enough to produce an estimated divergence of ~3X10-8bp of difference/bp/generation, considerably above that for single nucleotide substitutions alone.
So you guys just pretend that a 1 bp mutation is the same thing as one a million base pairs long!!!!
In terms of being a single mutational event it is. In terms of the effects of that mutation, especially on length, it isn't.
This could all be sorted out much more simply if you let us know exactly where your estimate of the mutation rate comes from so we can tell exactly what it is supposed to be measuring. You can trace all my numbers back to my references so why not give us the same courtesy.
TTFN,
WK

This message is a reply to:
 Message 144 by eggasai, posted 11-07-2006 7:21 PM eggasai has not replied

Replies to this message:
 Message 148 by derwood, posted 11-11-2006 9:49 AM Wounded King has not replied

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


Message 152 of 157 (464019)
04-22-2008 4:44 PM
Reply to: Message 151 by derwood
04-22-2008 2:45 PM


Wow, I didn't realise he was actually still arguing the same ridiculous point about how mutation rates are measured, I thought you just meant arguing about human brain evolution.
How dumb do you have to be to still think you are right and everyone else is wrong when dozens of independent people on disparate sites point out exactly the same flaws in your reasoning.
TTFN,
WK

This message is a reply to:
 Message 151 by derwood, posted 04-22-2008 2:45 PM derwood has replied

Replies to this message:
 Message 153 by derwood, posted 07-08-2008 2:04 PM Wounded King has not replied

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


Message 155 of 157 (474573)
07-09-2008 11:47 AM
Reply to: Message 154 by Dr Adequate
07-09-2008 6:27 AM


These ones should get points for trying at least.
I think this is slightly unfair. After all we want IDists and creationists to be trying to make coherent arguments with reference to the scientific literature. At least Eggasai and Randman seem to have some idea of what the right approach should be even if they do fall down on the details.
I think part of the problem is that they go straight to more recently published literature before they actually have a good understanding of evolutionary theory, genetics, or molecular biology. The problem is that they are often unwilling to admit that they don't know the basics.
TTFN,
WK

This message is a reply to:
 Message 154 by Dr Adequate, posted 07-09-2008 6:27 AM Dr Adequate has not replied

  
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