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Messages - Dean W

1

::)    Whereas 'negativity' is a completely abhorrent concept to Trump and his followers. 


Quote from: Con Air
Nathan Jones, A.K.A. Diamond Dog. Former general of the Black Guerillas. He blew up a meeting of the National Rifle Association saying, and I quote, "They represented the basest negativity of the white race."
2
Cernovich.  Enough said.  Honestly, Dave, what's wrong with you?  You'd have a better track record if you used a fucking Magic 8-Ball.
3
All you have to do is find us some mtDNA from Homo heidelbergensis, Homo rhodesiensis and/or Homo antecessor. But since they all lived hundreds of thousands of years ago, that might prove difficult.
I suspect there were probably many more Homo species running around than we have names for. Fossilization is rare - especially so in much of Africa. The notion of the "Progression of Man" - iconically captured in cartoons like this:



... continues to dominate many not-so-educated people's model of how we came to be. Especially not-so-educated people committed, consciously or subconsciously, to a "Platonic" paradigm, where there's some ideal, and Nature is trying to achieve it.

The "Tree of Life" concept is a step in the direction of reality.
And a recognition of the "bushiness" of that "tree" - where there is a whole lot more branching, sub-branching, and abortive twigs than the usual "tree" image conveys - is a further step in that direction.

But when the focus is as close-up as is the focus on human evolution, especially as DNA evidence becomes more available, the  tree/bush trunk/branch/twig analogy is misleading because it fails to take into account anastomoses of lineages. (Introgression of Neanderthal into the sapiens line is an example).

The "braided stream" image is the better analogy. And the overwhelming majority the diverging and rejoining rivulets don't  - and probably never will - have names.  That link, btw, is definitely worth reading for anyone who is at all uncertain about why "Socrates" is terminally befuddled on this subject.

Say what you want about the inaccuracy of "Progression of Man", Rudolph Zallinger rocked.  Dinosaurs and Other Prehistoric Reptiles shaped my life.

4
Quote
Worth repeating that it has already been established that there are very few differences between neanderthal and human.
https://www.ncbi.nlm.nih.gov/nuccore/253947345
https://www.ncbi.nlm.nih.gov/nuccore/253947345
Consider the position values in the arch. The authors cannot say what value their fanciful RSRS has in those positions. So they cannot account for those positions in their fanciful AFRICAN RSRS.
It is clear that you folks do not have a clue about what the positions in the arch mean.
I suggest that mt-MRCA evolved from Neanderthals in the Middle East. This is the most parsimonious phylogeny.
I like to see uncool happy.
Now someone can take an ancestor from Africa and describe that. Show us how parsimonious that is.

Quote
According to the recent African origin of modern humans theory, modern humans evolved in Africa possibly from Homo heidelbergensis, Homo rhodesiensis or Homo antecessor
Anyone?

I think our guests would appreciate Doug's assessment of where his phantasm Neandertals would fit in with the very real mtDNA evidence at our disposal.



Well, Doug?
5
At this point, I think our guests are asking themselves some fundamental questions.  Namely, let's pretend Doug's make believe Middle Eastern Neandertals actually existed.  And let's pretend their mtDNA somehow vindicated Doug's hypothesis.  What would a tree incorporating these imaginary Neandertal genomes look like?  If it can't be found within every single last possibility, what does that mean regarding Doug's imaginary hypothesis?

Here's four individuals.  Let's say all four died without leaving any children so none of them can possibly be a descendant of any of the others.

N  garden variety neandertal

N*  hypothetical Middle Eastern neandertal whose sister is on the line you think led to modern humans.

L3  member of haplogroup L3

L0  member of haplogroup L0

Here's every possible way a BLAST tree could come out if we compared their sequences.  In other words, every possible way they could be related.  One of them has to fit your hypothesis, if it can be correct in our dimension.

Give us the letter that matches it.

6
What would be good would be to take the actual evidence of the study and relate it to the idea of humans having evolved in the Middle East from a branch of Middle Eastern Neanderthals. I do not expect that you folks would be able to do that. I understand.
Right.  Let's see how your imaginary leprechaun Middle Eastern Neandertals would possibly fit in.  A good start would be for you to pick a tree, don't you think?

Doug, you have to know that your inability to specify a tree portraying your proposed relationships between modern humans and neandertals is a deathblow to your hypothesis.  I'm here to rescue you on that score.  I realize we'll have to start with baby steps and then go from there.

Here's four individuals.  Let's say all four died without leaving any children so none of them can possibly be a descendant of any of the others.

N  garden variety neandertal

N*  hypothetical Middle Eastern neandertal whose sister is on the line you think led to modern humans.

L3  member of haplogroup L3

L0  member of haplogroup L0

Here's every possible way a BLAST tree could come out if we compared their sequences.  In other words, every possible way they could be related.  One of them has to fit your hypothesis, if it can be correct in our dimension.

Give us the letter that matches it.




7
I was thinking about that paper by our old friends Green et al. (2009), specifically, what would happen if we expanded it by including every single Neandertal mtDNA sequence available.
Quote
A complete Neandertal mitochondrial genome sequence determined by high-throughput sequencing

A complete mitochondrial (mt) genome sequence was reconstructed from a 38,000-year-old Neandertal individual using 8,341 mtDNA sequences identified among 4.8 Gb of DNA generated from ~0.3 grams of bone. Analysis of the assembled sequence unequivocally establishes that the Neandertal mtDNA falls outside the variation of extant human mtDNAs and allows an estimate of the divergence date between the two mtDNA lineages of 660,000±140,000 years. Of the 13 proteins encoded in the mtDNA, subunit 2 of cytochrome c oxidase of the mitochondrial electron transport chain has experienced the largest number of amino acid substitutions in human ancestors since the separation from Neandertals. There is evidence that purifying selection in the Neandertal mtDNA was reduced compared to other primate lineages suggesting that the effective population size of Neandertals was small.

Among the humans, the number of differences ranges from 2 to 118 and is bimodal. The peak with a mode around 99 differences contains comparisons that involve at least one member of deep clades containing sub-Saharan African mtDNAs. The peak with a mode around 44 differences involves comparisons between individuals outside these clades. By contrast, the number of differences between human mtDNAs and the Neandertal mtDNA ranges from 201 to 234 and is unimodal. Thus, the Neandertal mtDNA falls outside the variation of extant humans even when nucleotide differences, uncorrected for multiple substitutions, are counted.




So, I BLASTed every available complete Neandertal sequence against the rCRS.

Spoiler (click to show/hide)

The results ranged from 204 to 265 differences between the rCRS and the Neandertals, roughly two times the difference between modern humans.

Now, we know that the ancestor of a group of individuals should differ from them by roughly half the amount they differ from each other.

Spoiler (click to show/hide)

I think our guests require more than whiny assertions of imaginary Middle Eastern Neandertals with mysterious mtDNA such that Doug cannot even propose a tree incorporating them.

Hasn't this silliness gone on long enough?
8
Cool, Doug's superficial and dilletantish observations are both contained in my rigorous analysis.  Outgroups settling ties is evidently the way to go.

Spoiler (click to show/hide)
9
I was thinking about the outgroup "breaking the tie" regarding the RSRS.  So, I did a little experiment.

I BLASTED the rCRS, an L0, three Neandertals, and three Denisovans.

Then I went through the whole sequence and tallied up instances where the rCRS and L0 differed (a tie) and ALL SIX of the Neandertals and Denisovans had the same value, no matter which modern human it corresponded to (sort of a super outgroup).  Then I looked up the position in Phylotree and scored it a YES if it was the same as the Neandertals and Denisovans and a NO if it wasn't.  I've include the Phylotree change references.

Score: 54 YES, 3 NO

Spoiler (click to show/hide)

BLAST table

ETA:  Went back and checked again, I missed a bunch.
10
I think this has been pointed out before, but the Neandertals from which we've extracted DNA are all too young (maybe 130 kya, tops) to be ancestral to modern humans anyway.  So, analyzing them as cousins is appropriate in any case.
11
I haven't looked at the paper that closely, but it had previously been reported that  Neanderthals were closer to modern humans in mtDNA but closer to Denisovan in nDNA. So basically they seem to be proposing that the later Neanderthal mtDNA was introgressed from a lineage more closely related to sapiens, sometime between ~ 400 and ~ 50 kya.

So, wouldn't that make Denisovan/sapiens mtDNA comparisons a better indicator of the Neanderthal/sapiens divergence than Neanderthal*/sapiens ones?

* The mtDNA introgressed ones.
12
It turns out NCBI has H. heidelbergensis on file.



BLAST tree



Damn, when did they sequence that?  Do you have the ascension number?

So, from your BLAST they are not ancestral to modern humans.


Subsequent publications have revised that, and concluded it was an early Neanderthal.
Sorry -  don't have the reference handy.

ETA: 
https://www.nature.com/news/oldest-ancient-human-dna-details-dawn-of-neanderthals-1.19557
Quote

The nuclear DNA, Meyer's team reports in Nature on 14 March, shows that the Sima hominins are in fact early Neanderthals. And its age suggests that the early predecessors of humans diverged from those of Neanderthals between 550,000 and 765,000 years ago -- too far back for the common ancestors of both to have been Homo heidelbergensis, as some had posited.


Oh well, at least I got to be all excited for a couple of minutes.
It's still pretty exciting!

Here's the 2016 paper  (same research group) where they conclude it's an early neanderthal*, not heidelbergensis.
Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins

* at least it's closer to neanderthal than to denisovan, therefore more recent than the split between the two, therefore post-heidelbergensis

From the abstract.

Quote
...A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.

What do they mean by "turned over"?
13
Spoiler (click to show/hide)

One consideration is that the numbering system is based on the rCRS or the RSRS.

uncool already corrected me on that point, but thanks.
I'm assuming that Phylotree has already aligned the sequences.  Is that not correct?



Yeah, here's what is has at the top of the full tree:

Quote
PhyloTree.org - mtDNA tree Build 17 (18 Feb 2016)                   
 Citation: van Oven M, Kayser M. 2009. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat 30(2):E386-E394.           
                         
 Nucleotide position numbers are consistent with both the rCRS and the RSRS reference sequences.               
 Mutations are given in forward evolutionary time direction in the format [ancestral base][position number][derived base], e.g. "G15043A".             
 In case of a transversion, the derived allele is shown in lowercase instead of uppercase, e.g. "C5178a".               
 Insertions are indicated by the position number preceding the insertion followed by a dot (.), the relative insert position, and the inserted base(s), e.g. "2156.1A".           
 Deletions are indicated by the letter "d" following the (range of) position number(s) involved, e.g. "A249d" or "8281-8289d".             
 Mutations that are reversions to an ancestral state (back mutations) are indicated with an exclamation mark (!), two exclamation marks for a double back mutation (!!), etc., e.g. "A15301G!".         
 Coding-region mutations (np 577-16023) are shown in black; control-region mutations (np 16024-576) in blue.               
 Mutations between brackets () are recurrent/unstable within the respective clade, or are yet uncertain based on current data.             
 Mutation motifs in italic are preliminary and are likely to be further refined as additional sequences become available.               
 The mutations 309.1C(C), 315.1C, AC indels at 515-522, A16182c, A16183c, 16193.1C(C) and C16519T/T16519C were not considered for phylogenetic reconstruction and are therefore excluded from the tree.       
 Accession numbers provided at the tips of branches are representative examples of mtDNA sequences available at GenBank or from individuals included in HapMap/1000Genomes.         
 It may be convenient to use the Find function (Ctrl+F) of your browser to search for a particular mutation or haplogroup.
14
It turns out NCBI has H. heidelbergensis on file.



BLAST tree



Damn, when did they sequence that?  Do you have the ascension number?

So, from your BLAST they are not ancestral to modern humans.


Subsequent publications have revised that, and concluded it was an early Neanderthal.
Sorry -  don't have the reference handy.

ETA: 
https://www.nature.com/news/oldest-ancient-human-dna-details-dawn-of-neanderthals-1.19557
Quote

The nuclear DNA, Meyer's team reports in Nature on 14 March, shows that the Sima hominins are in fact early Neanderthals. And its age suggests that the early predecessors of humans diverged from those of Neanderthals between 550,000 and 765,000 years ago -- too far back for the common ancestors of both to have been Homo heidelbergensis, as some had posited.


Oh well, at least I got to be all excited for a couple of minutes.
15
Here's the paper about getting the H. heidelbergensis mtDNA.

A mitochondrial genome sequence of a hominin from Sima de los Huesos
16
I count 148 on the "loop", although it's quite easy to lose track.

There are 20 differences between RNRS and the first Neanderthal specimen.

Of the 56 differences between RSRS and rCRS:

2 (146 and 152) are in common with the Neanderthal specimen, but not RNRS.
4 are reversals of each other (182, 15301)
5 "undo" the "loop" (195, 2706, 13506, 13650, 16187)
The other 45 add additional differences.
So: 148 + 45 - 5 = 188 differences between rCRS and RNRS. 2 of the differences between RNRS revert, and the other 18 add, so 188 - 2 + 18 = 204 differences between rCRS and FM865411.

These are literally the first examples I could find. I stand by my statement: low hundreds.


Damn, got logged out in the middle of responding to this.

I also got 148 for the arch.
Not sure why you are referring to rCRS or FM865411.  As far as I can tell So-crates has not specified FM865411 as the ancestral Neanderthaland and rCRS is not L3 so why is it relevant?

Why do the five that you list, undo the loop? 

Until So-crates provides a Neanderthal sequence to compare, the only relevant sequences that I see are RNRS, RSRS and L3.


I wanted to deal with specimens, not parsimony reconstructions, to demonstrate that based on the data alone, we can see the hundreds of differences.

The 5 "undo" the loop because if RNRS was in one state, then RSRS would be in the opposite state (since A<->G and C<->T are by far more common), and then rCRS would be in the same state as RNRS.

Ok, but what is the relevance of rCRS?  If it isn't relevant then 2706 is not relevant.


I thought I remembered rCRS was itself the sequence of a specific person. So I chose them, as the easiest specific person I could find.

That's fine but rCRS is a bit removed from L3.  Sure you could reverse the changes between rCRS and L3, but I don't see it justified to include them in any count of an RSRS to L3 difference.  I was referring to L3a1a which is 13 different from L3 versus 18 between L3 and rCRS.



One consideration is that the numbering system is based on the rCRS or the RSRS.
17
It turns out NCBI has H. heidelbergensis on file.



BLAST tree



Damn, when did they sequence that?  Do you have the ascension number?

So, from your BLAST they are not ancestral to modern humans.



KF683087.1

Turns out the second one is just a copy, they're 100% identical.  From the tree, I'd say they aren't ancestral, in that they apparently share a more recent ancestor with Denisovans than with us, at least on the mtDNA side.  Since nuclear DNA puts Denisovans on the same branch as Neandertals, there've been papers surmising introgression between Denisovans and an unidentified hominin.
18
It turns out NCBI has H. heidelbergensis on file.



BLAST tree
19
I count 148 on the "loop", although it's quite easy to lose track.

There are 20 differences between RNRS and the first Neanderthal specimen.

Of the 56 differences between RSRS and rCRS:

2 (146 and 152) are in common with the Neanderthal specimen, but not RNRS.
4 are reversals of each other (182, 15301)
5 "undo" the "loop" (195, 2706, 13506, 13650, 16187)
The other 45 add additional differences.
So: 148 + 45 - 5 = 188 differences between rCRS and RNRS. 2 of the differences between RNRS revert, and the other 18 add, so 188 - 2 + 18 = 204 differences between rCRS and FM865411.

These are literally the first examples I could find. I stand by my statement: low hundreds.

That jives pretty well with what I got from BLASTing.  My numbers are a little lower, but I didn't include reversals, just the end differences.

Spoiler (click to show/hide)

Did they include insertions/deletions (i.e. 521-522)?  FM865411 only has 16564 base pairs.  Not sure what a reference L3 has but L3a1a has 16567.

And of course rCRS has 16569, but not sure of the relevance of rCRS.



They give gaps, but I took the easy road.
20
I count 148 on the "loop", although it's quite easy to lose track.

There are 20 differences between RNRS and the first Neanderthal specimen.

Of the 56 differences between RSRS and rCRS:

2 (146 and 152) are in common with the Neanderthal specimen, but not RNRS.
4 are reversals of each other (182, 15301)
5 "undo" the "loop" (195, 2706, 13506, 13650, 16187)
The other 45 add additional differences.
So: 148 + 45 - 5 = 188 differences between rCRS and RNRS. 2 of the differences between RNRS revert, and the other 18 add, so 188 - 2 + 18 = 204 differences between rCRS and FM865411.

These are literally the first examples I could find. I stand by my statement: low hundreds.

That jives pretty well with what I got from BLASTing.  My numbers are a little lower, but I didn't include reversals, just the end differences.

Spoiler (click to show/hide)
21
As has been pointed out repeatedly by others, the outgroup is only necessary if we want to reconstruct the genome of the RSRS.  Extant humans are all that's necessary to construct a tree based on pairwise comparisons.  How are witless (yet mysteriously very knowledgeable and well-educated) researchers going to "slip" Neandertal mtDNA into comparisons with no Neandertals?  And what do we notice about the branching patterns of exclusively modern humans relative to their geographical locations?

22
I BLASTed the rCRS against Neandertal FM865411.  There were 208 differences.

Here are the changes between the RSRS and the rCRS from Phylotree and the differences between the RNRS and Neandertal FM865411 from the "arch" chart we all know and love:
Spoiler (click to show/hide)


Supporting information
Spoiler (click to show/hide)

When the changes between RSRS/rCRS, L3root/rCRS, and RNRS/FM865411 are all accounted for (see above), here's how things come out.

Differences:

L3root:RNRS 171

RSRS:RNRS  145

Didn't Doug claim that there were only 25 differences between the RNRS and the base of L3?  He never shows his work in any coherent manner, but still, how could somebody look at the "arch" chart and come up with that?

The RSRS still stands as the unchallenged root of the tree.
23
This is a much delayed ETA.  I should have included the positions between the L3 root and the rCRS after all.  They didn't change relative differences but did change the absolute number by 1.  I wanted to correct this because later I'm going to do this again comparing the RSRS, L3 root, and the RNRS.

I BLASTed the rCRS against an L0.  There were 91 differences.  Then I listed all the differences between the RSRS and the rCRS in Phylotree, capturing the differences between the RSRS and the root of L3 along the way.

Here they are:
Spoiler (click to show/hide)

There were 51 differences between the rCRS and the RSRS, 18 differences between the rCRS and the root of L3.

We're going to compare having the L3 root as the root of the tree and having the RSRS as the root of the tree when it comes to the differences between them, the rCRS, and an L0.

So now we make our table incorporating the BLAST results, using the order from Phylotree for convenience.  I've omitted position 182 because the reversal occured before the L3 root, and A15301G! doesn't matter because we only need the changes up to L3 root for our comparisons with L0.

I've given the value at each position where the RSRS and L3 root differ, based on the Phylotree list.  The value for the L0 is from the BLAST.  If the RSRS and the L0 are the same, the RSRS gets a plus, and the same for the L3 root and the L0.  The total number of pluses for each gets subtracted from the 91 differences between the rCRS and the L0.  That's because the difference between the RSRS or L3 root and the rCRS turned it into an identity with the L0.
Spoiler (click to show/hide)


Supporting information.  Anybody can pull up Phylotree if they want on their own.
Spoiler (click to show/hide)
Differences:

L3root:rCRS 18
L3root:L0   87

RSRS:rCRS   51
RSRS:L0     59
24
I BLASTed the rCRS against an L0.  There were 91 differences.  Then I listed all the differences between the RSRS and the rCRS in Phylotree, capturing the differences between the RSRS and the root of L3 along the way.

Here they are:
Spoiler (click to show/hide)

There were 51 differences between the rCRS and the RSRS, 18 differences between the rCRS and the root of L3.

We're going to compare having the L3 root as the root of the tree and having the RSRS as the root of the tree when it comes to the differences between them, the rCRS, and an L0.

So now we make our table incorporating the BLAST results, using the order from Phylotree for convenience.  I've omitted position 182 because the reversal occured before the L3 root, and A15301G! doesn't matter because we only need the changes up to L3 root for our comparisons with L0.

I've given the value at each position where the RSRS and L3 root differ, based on the Phylotree list.  The value for the L0 is from the BLAST.  If the RSRS and the L0 are the same, the RSRS gets a plus, and the same for the L3 root and the L0.  The total number of pluses for each gets subtracted from the 91 differences between the rCRS and the L0.  That's because the difference between the RSRS or L3 root and the rCRS turned it into an identity with the L0.
Spoiler (click to show/hide)


Supporting information.  Anybody can pull up Phylotree if they want on their own.
Spoiler (click to show/hide)
Differences:

L3root:rCRS 18
L3root:L0   88

RSRS:rCRS   51
RSRS:L0     60

Just noticing, 88/18 = 4.9, probably because I used a different L0 than uncool did.  By way of contrast, 60/51 = 1.2, which strikes me at least as being considerably smaller than 4.9.  Like 4 times smaller.  That seems significant.



25
Now that Doug has enthusiastically embraced Neandertals from everywhere they lived as relevant, this deserves reposting.

This is every single Denisovan and Neandertal in the NCBI database.  At what point do Doug's ridiculous fantasies deserve anything less than complete and justifiable rejection?