Human evolution for Sean Pitman
John Harshman
this post I originally wrote for Zoe. Since Zoe is incapable of
comprehending it, perhaps you would be interested instead.
It's a small part of the evidence for human relationships to the other
apes, which as I recall you disagree with. Perhaps you could enlighten
me on the counterarguments.
Here is a set of DNA sequences. They come from two mitochondrial genes,
ND4 and ND5. If you put them together, they total 694 nucleotides. But
most of those nucleotides either are identical among all the species
here, or they differ in only one species. Those are uninformative about
relationships, so I have removed them, leaving 76 nucleotides that make
some claim. I'll let you look at them for a while.
[ 10 20 30 40 50]
[ . . . . .]
+ 1 2++ 3 11 +4 3 ++ 52+1 2615+4 14+ 3 3+6+
gibbon ACCGCCCCCA TCCCCTCCCT CAAGTCCTAT CCAATCTACT GTACTTTGCC
orangutan ACCACTCCCA CCCTTCCTCC TAAGACTCAC ACAACTCGCC ACACCTCGTC
human GTCATCATCC TTCTTTTTTT AGGAATTTCC TCTCTCCGTC ACGCTCTACT
chimpanzee ATTACCATTC CTTTTTTCCC CGGATTCTCC CTTCTTCATT ATGTCTCATT
gorilla GTTGTTATTA CCTCCCTTTC AAGAACCCCT TTCACCTATC GCGTCCCACT
[ 60 70 ]
[ . . ]
+++ +++1 + ++ 2 + +++
gibbon CCTACAGCCC AGCCAAACGA CACTAA
orangutan CCTACCGCCT AGCCATTTCA CACTAA
human CCCCTTATTT TCTTGTCCGG TGACCG
chimpanzee TTCCTCATTT TCTTACTCAG TGACCG
gorilla TTCCTTATTC TTTCGCCTAG TGATTA
I've marked with a plus sign all those sites at which gibbon and
orangutan match each other, and the three African apes (including
humans) have a different base but match each other. These sites all
support a relationship among the African apes, exclusive of gibbon and
orangutan. You will note there are quite a lot of them, 24 to be exact.
The sites I have marked with numbers from 1-6 contradict this
relationship. (Sites without numbers don't have anything to say about
this particular question.) We expect a certain amount of this because
sometimes the same mutation will happen twice in different lineages; we
call that homoplasy. However you will note that there are fewer of these
sites, only 22 of them, and more importantly they contradict each other.
Each number stands for a different hypothesis of relationships; for
example, number one is for sites that support a relationship betwen
gibbons and gorillas, and number two is for sites that support a
relationship between orangutans and gorillas (all exclusive of the
rest). One and two can't be true at the same time. So we have to
consider each competing hypothesis separately. If you do that it comes
out this way:
hypothesis sites supporting
African apes (+) 24
gibbon+gorilla (1) 6
orangutan+gorilla (2) 4
gibbon+human (3) 4
gibbon+chimp (4) 3
orangutan+human (5) 2
orangutan+chimp (6) 2
I think we can see that the African ape hypothesis is way out front, and
the others can be attributed to random homoplasy. This result would be
very difficult to explain by chance.
By itself, this is pretty good evidence for the African ape connection.
But if I did this little exercise with any other gene I would get the
same result too. (If you don't believe me I would be glad to do that.)
Why? I say it's because all the genes evolved on the same tree, the true
tree of evolutionary relationships. That's the multiple nested hierarchy
for you.
So what's your alternative explanation for all this? You say...what?
It's because of a necessary similarity between similar organisms? But
out of these 76 sites with informative differences, only 18 involve
differences that change the amino acid composition of the protein; the
rest can have no effect on phenotype. Further, many of those amino acid
changes are to similar amino acids that have no real effect on protein
function. In fact, ND4 and ND5 do exactly the same thing in all
organisms. These nested similarities have nothing to do with function,
so similar design is not a credible explanation.
God did it that way because he felt like it? Fine, but this explains any
possible result. It's not science. We have to ask why god just happened
to feel like doing it in a way that matches the unique expectations of
common descent.
Ron Okimoto
This won't work. You are trying to sneak in the concept of nested
similarity and Sean won't bite. If he learns what nested similarity
really is he won't be able to claim that it is due to similar designs
anymore. You can't fight Sean's willful ignorance. Look, he is still
claiming an exponential increase in neutral mutations without any
backing except his say so. I don't think that even Behe or Dembski
make that claim.
Ron Okimoto
John Harshman
Ron Okimoto wrote:
> John Harshman <jhar...@calacademy.org> wrote in message news:<3F85D850...@calacademy.org>...
[snip insightful demonstration of common descent]
>
> This won't work.
No doubt. Very few arguments, if any, have ever convinced a committed
creationist. But what else is this newsgroup for?
> You are trying to sneak in the concept of nested
> similarity and Sean won't bite. If he learns what nested similarity
> really is he won't be able to claim that it is due to similar designs
> anymore. You can't fight Sean's willful ignorance.
No, but you can poke it a bit to investigate its shape. Besides, I hate
wasting the work that went into this. I may just repeat it every time a
halfway literate creationist drops in.
I'm suspecting that Dr. Sean will handle this thread by ignoring it,
unfortunately.
> Look, he is still
> claiming an exponential increase in neutral mutations without any
> backing except his say so. I don't think that even Behe or Dembski
> make that claim.
Shhh. Now you'll just make him defend his particular obsession by
repeating his claims even louder. That reduces still further the already
small chance that he'll respond in any meaningful way to this.
Bobby D. Bryant
> God did it that way because he felt like it? Fine, but this explains any
> possible result. It's not science. We have to ask why god just happened
> to feel like doing it in a way that matches the unique expectations of
> common descent.
Made Adam from a gorilla's rib?
--
Bobby Bryant
Austin, Texas
Frank J
> this post I originally wrote for Zoe. Since Zoe is incapable of
> comprehending it, perhaps you would be interested instead.
>
> It's a small part of the evidence for human relationships to the other
> apes, which as I recall you disagree with.
He may "disagree" with "human relationship to other apes" *on record*,
but don't forget that he raved about Michael Behe, who has no problem
at all with it. Which leads me to be highly suspect as to whether he
disagrees with it in private.
> Perhaps you could enlighten
> me on the counterarguments.
I hope that you don't mean the same old arguments-from-incredulity,
but arguments that support an alternative hypothesis, such as the 2
"independent origins" ones to which I often refer.
Stop making his job easier by bringing God into the picture. What you
really want is for him to provide positive support for an independent
origins (IO)hypothesis; something like a "genomic potential" but with
a lot more than the idle speculation of its few serious advocates.
Given the overwhelming support for common descent provided by multiple
lines of independent evidence, any suggestion of an IO alternative has
become an "extraordinary claim" which demands "extraordinary
evidence." Most anti-evolutionists know that, which is why they rarely
address IO directly, but rather trick the audience to infer it from
their strawman arguments against "Darwinism." If the serious advocates
of IO (e.g. Schwabe and Senapathy) cannot provide extraordinary
evidence, can we expect the "bait and switch" strategists to even try?
John Harshman
Frank J wrote:
> John Harshman <jhar...@calacademy.org> wrote in message news:<3F85D850...@calacademy.org>...
[snip]
> Given the overwhelming support for common descent provided by multiple
> lines of independent evidence, any suggestion of an IO alternative has
> become an "extraordinary claim" which demands "extraordinary
> evidence." Most anti-evolutionists know that, which is why they rarely
> address IO directly, but rather trick the audience to infer it from
> their strawman arguments against "Darwinism." If the serious advocates
> of IO (e.g. Schwabe and Senapathy) cannot provide extraordinary
> evidence, can we expect the "bait and switch" strategists to even try?
No we can't. But we can rub their noses in it, which is the purpose of
my post. No response yet from Dr. Sean, which is probably his best strategy.
R. Dunno
He seems to disappear in other discussions if you ask for details
of his vast neutral gaps and multiple-proteins arguments wrt closely
related primates like chimps and humans.
Frank J
Michael Behe, whom Sean raved about, admitted that chimps and humans
share common ancestors, and thus saw no need to propose a recent
abiogenesis of one or more eukaryotes, much less a theory for it. One
then would expect Sean to challenge Behe directly on this point. In
fact, given that Behe does not have "a prior commitment to naturalism"
one would expect Sean to consider Behe a more reasonable opponent than
us "dogmatic disciples of Darwin."
Sean Pitman
> this post I originally wrote for Zoe. Since Zoe is incapable of
> comprehending it, perhaps you would be interested instead.
I doubt Zoe is incapable of comprehending it, but anyway, I'll take a
look.
> It's a small part of the evidence for human relationships to the other
> apes, which as I recall you disagree with. Perhaps you could enlighten
> me on the counterarguments.
Actually, I don't think we known enough about the functional genetic
differences between humans and chimps to support or counter an
evolutionary relationship adequately. The demonstration of functional
and nonfunctional similarities is not enough to support the theory of
common evolutionary origins. The *functional differences* are what
need to be explained in order to determine a common evolutionary
origin over intelligent design. At least from my perspective, these
differences are not characterized well enough to exclude the
possibility of a common evolutionary origin between humans and chimps.
Personally, I do not believe that humans and chimps share a common
ancestor, but I cannot adequately support this position from genetic
evidence at this time. Of course, the evidence does not adequately
support your evolutionary position either at this point in time - but
more on that below.
Correct me if I am wrong, but the basic question here is, why do
humans share more similar "nested" sequences with gorillas and chimps
than with gibbons and orangutans if all of these differences are
essentially neutral with regard to function? This is a most
interesting question as it seems like there would be no reason for
such nesting aside from differences in time from the most recent
common ancestor. The question is, are these similarities and
differences really all that statistically significant?
Your whole line of reasoning is especially interesting because, based
on real-time studies of human mitochondrial mutation rates (from known
historical families instead of assumed evolutionary scenarios), the
average mutation rate for certain stretches of mtDNA runs about 2.5
mutations/base pair/million years or 1 mutation in this 600bp sequence
every 33 generations (660 years). What does this mean? It means
something very interesting if the mutation rates for the sequences you
are presenting here are similar to this rate of 2.5mut/bp/myr. I
mean, when did the "most recent common ancestor" between all of these
species live? If accurate, this mutation rate means that every single
base pair in a stretch of mitochondrial DNA would have been
mutated/changed at least *twice* in only one million years - making
any phylogenetic analysis meaningless with regards to any sort of
evolutionary relationship that is supposed to span something like 6 to
8 million years.
Beyond this, you fail to list the intraspecies range of variation. I
assume that the sequences you listed here either represent average
sequences or the sequences of a single individual from each species.
For example, for certain neutral sequences in mtDNA of around 600bp in
length the *average* difference between humans is about 18 mutations
(Genetics vol. 15, April 1997, pp. 363-367) - with a *range* that is
triple that at around 54 mutations. By extrapolation, your stretch of
76 base pairs listed here should have an intrahuman average of 2 or so
differences with a range of 6 differences. If the other species
averaged out along these same lines, your numbers could be off by as
much as 12 differences depending upon which individuals from each
species group were compared. Actually though, the average range
between humans is around 3.5% while chimps have a much higher average
range of 15% and gorillas are even higher at 19%. This fairly wide
range of potential gene pool variation shoots the statistical
significance of your phylogenic trees all to bits - or so it seems to
me.
http://naturalselection.0catch.com/Files/dnamutationrates.html
http://naturalselection.0catch.com/Files/earlyman.html
In fact, some scientists, such as D. Melnick and G. Hoelzer (Columbia
University), have tested the assumptions of mtDNA based phylogenic
relationships and concluded: "Our results suggest serious problems
with use of mtDNA to estimate "true" population genetic structure, to
date cladogenic events, and in some cases, to construct phylogenies"
(Melnick, D. and Hoelzer, G., 1992. What in the study of primate
evolution is mtDNA good for? American Journal of Physical
Anthropology, Supplement 14, p. 122.). Likewise, Jonathan Marks (Yale
University) declared mtDNA determined relationships to be highly
biased: "Most analysis of mitochondrial DNA are so equivocal as to
render a clear solution impossible, the preferred phylogeny relying
critically on the choice of outgroup and clustering technique" (Marks,
J., Chromosomal evolution in primates. The Cambridge Encyclopedia of
Human Evolution, S. Jones, R. Martin, and D. Pilbeam (eds), Cambridge
University Press, Cambridge, p. 302., 1992). Further, an August 2002
study of such phylogenetic trees used to analyse Neandertal sequences,
by Gabriel Guitierrez et al., from the Universidad de Sevilla, Spain,
was published in the well known journal, Molecular Biology and
Evolution entitled, "A Reanalysis of the Ancient Mitochondrial DNA
Sequences Recovered from Neandertal Bones." Consider their conclusions
from the following abstract:
"Recent reports analyzing mitochondrial DNA sequences from Neandertal
bones have claimed that Neadnertals and modern humans are different
species. The phylogenetic analyses carried out in these articles did
not take into account the high substitution rate variation among sites
observed in the human mitochondrial D-loop region and also lack an
estimation of the parameters of the nucleotide substitution model. The
separate phylogenic position of Neandertal-Human and Human-Human
pairwise distance distributions overlap more than what previous
studies suggested. We also show that the most ancient Neandertal HVI
region is the most divergent when compared with modern human
sequences. However, the opposite would be expected if the sequence had
not been modified since the death of the specimen. Such incongruence
is discussed in the light of diagenetic modifications in ancient DNA
sequences."
In the body of this paper, there were several other statements of
interest:
"The NSG [The conclusions of Krings et al., based on their "Neandertal
sequencing groups"] reported that the pairwise comparisons between the
Neandertal and human sequences demonstrate that Neandertals are
outside of modern human D-loop variability. In particular, Krings et
al., (1997) stated that 'a total of 0.002% of the pairwise comparisons
between human mtDNA sequences were larger than the smallest difference
between the Neandertal and the humans.' We think that this point
merits further analysis. The current database is biased because of the
overrepresentation of some populations and the underrepresentation of
others. For instance, the MOUSE database contains 6,012 entries for
the HVI region, but 31% of the entries belong to only 20 populations
out of 206 populations represented (10% of the total populations). The
extreme cases are 306 Koreans, 126 Yaps, 120 Cayapa Amerindians, 119
Mandeka, 115 Palau, and 100 white British. There are also 1,417
entries of undetermined population (40% of them are from North America
and 23% European, but only 9% are from Africa). Thus, African
populations containing the most ancient lineages and the highest
variation are underrepresented in the database.
Because of the database overrepresentation of some human populations,
the distribution of pairwise distances is biased. A large part of
pairwise comparisons are made between individuals belonging to the
same population. Likewise, it is expected that most individuals from a
single population will show similar distances to a given outgroup
(Neandertal, in this case). To overcome this problem, we considered
another sample of the human variation. We first sorted the HVI
sequences in our data set according to it uncorrected distance to the
reference sequence (Anderson et al. 1981). Then we grouped them into
171 classes, containing equidistant sequences (considering four
decimals), and chose one sequence at random from each class. The
computation of pairwise distances between 171 randomly selected
sequences and the Neandertals rendered 1.6% of human-human comparisons
larger than the smallest difference between Neandertals and humans.
Likewise, 27% of the comparisons are lower than the largest
human-human difference. This result suggests that Neandertals
sequences are not so different from those of extant humans, in
contrast to the NSG [Krings et. al.] claims."
Guitierrez et al., went on to note that:
"The main conclusion can be extracted from our analyses: the
phylogenetic position of the ancient DNA sequences recovered from
Neandertal bones is sensitive to the phylogenetic methods employed. It
depends on the model of nucleotide substitution, the branch support
method, and the set of data used. Adcock et al. (2001) recovered HVI
sequences of archaic human bones from Australia, and their phylogenic
analysis showed that two of the specimens were outgroups even for the
most ancient African lineages. They concluded that this is evidence
supporting the multiregional hypothesis. However, a second analysis
carried out by Cooper et al. (2001) that took into account the
heterogeneity of rates between sites and a large sample of modern
humans, showed that both HVI sequences are located among extant
humans. This case illustrates the influence of the nucleotide
substitution model on the phylogenetic reconstruction of the human
D-loop region. The NSG studies used poor parameter models of
nucleotide substitution for their analysis, whereas we opted for
complex (parameter rich) models following the likelihood ratio test...
We believe that the likelihood mapping values supporting Neandertals
as a different species might be artifactually increased."
- Gutierrez, G., Sanchez, D., Marin, A. A Reanalysis of the
Ancient Mitochondrial DNA Sequences Recovered from Neandertal Bones,
Molecular Biology and Evolution, 19(8):1359-1366. 2002.
- Krings, M., Stone, A., Schmitz, R.W., Krainitzki, H., Stoneking, M.
and Pääbo, S., 1997. Neandertal DNA sequences and the origin of modern
humans. Cell, 90:19–30.
http://naturalselection.0catch.com/Files/earlyman.html
Guitierrez also noted that depending upon the control region chosen,
he could put a certain population of African humans as an outgroup
with chimps and include Neandertals with modern humans. Certainly
this is extremely politically incorrect, but that is the nature of
using such mtDNA phylogenies that have no statistical validity beyond
a few hundred generations at best.
So, to be honest, you must admit that your mtDNA phylogenetic
comparison here has a few potential flaws of some significance. Given
these potential problems, please do explain to me again the
statistical relevance of your position . . .
Sean
John Harshman
Sean Pitman wrote:
> John Harshman <jhar...@calacademy.org> wrote in message news:<3F85D850...@calacademy.org>...
>
>>As long as you around again, I would sure like to see your response to
>>this post I originally wrote for Zoe. Since Zoe is incapable of
>>comprehending it, perhaps you would be interested instead.
>
> I doubt Zoe is incapable of comprehending it, but anyway, I'll take a
> look.
You overestimate Zoe's abilities (or perhaps I should say inclinations)
for comprehension. But thanks for responding. I take back some bad
things I said about you previously.
>>It's a small part of the evidence for human relationships to the other
>>apes, which as I recall you disagree with. Perhaps you could enlighten
>>me on the counterarguments.
>
> Actually, I don't think we known enough about the functional genetic
> differences between humans and chimps to support or counter an
> evolutionary relationship adequately. The demonstration of functional
> and nonfunctional similarities is not enough to support the theory of
> common evolutionary origins. The *functional differences* are what
> need to be explained in order to determine a common evolutionary
> origin over intelligent design.
Once again you are confusing two separate issues. Intelligent design is
perfectly compatible with common evolutionary origin. I'm talking here
about common descent, and not about the mechanism that causes particular
mutations to occur.
> At least from my perspective, these
> differences are not characterized well enough to exclude the
> possibility of a common evolutionary origin between humans and chimps.
To say the least. How well would you have to characterize them to do
that? From my perspective, the differences are characterized well enough
to confirm common descent beyond any reasonable doubt. But let's just
look at the example I give below.
> Personally, I do not believe that humans and chimps share a common
> ancestor, but I cannot adequately support this position from genetic
> evidence at this time. Of course, the evidence does not adequately
> support your evolutionary position either at this point in time - but
> more on that below.
I'm interested in the reason for your belief in the absence of evidence.
If you can't support it, how can you hold it?
Why yes they are. Would you like to perform a statistical test on these
data? Pick your favorite.
> Your whole line of reasoning is especially interesting because, based
> on real-time studies of human mitochondrial mutation rates (from known
> historical families instead of assumed evolutionary scenarios), the
> average mutation rate for certain stretches of mtDNA runs about 2.5
> mutations/base pair/million years or 1 mutation in this 600bp sequence
> every 33 generations (660 years).
The operative phrase here is "for certain stretches". You are talking
about the hypervariable region of the D-loop. There's a reason it's
called hypervariable. The mutation rate in that region is orders of
magnitude higher than the mutation rate in, say, ND-3. So your whole
discussion that relies on assuming this amazingly high rate is
irrelevant to the question.
(As a digression, let's assume your mutation rate is correct. That would
be sufficient, as you state, to completely randomize all the sequences
over a fairly short period of time. If so, then what's your explanation
for the highly non-random pattern of similarities?)
> What does this mean? It means
> something very interesting if the mutation rates for the sequences you
> are presenting here are similar to this rate of 2.5mut/bp/myr. I
> mean, when did the "most recent common ancestor" between all of these
> species live? If accurate, this mutation rate means that every single
> base pair in a stretch of mitochondrial DNA would have been
> mutated/changed at least *twice* in only one million years - making
> any phylogenetic analysis meaningless with regards to any sort of
> evolutionary relationship that is supposed to span something like 6 to
> 8 million years.
>
> Beyond this, you fail to list the intraspecies range of variation. I
> assume that the sequences you listed here either represent average
> sequences or the sequences of a single individual from each species.
Single individuals. Individual variation in most species at these loci
averages much less than 1%, and contributes a negligible amount of
confusion. We can afford to ignore it.
> For example, for certain neutral sequences in mtDNA of around 600bp in
> length the *average* difference between humans is about 18 mutations
> (Genetics vol. 15, April 1997, pp. 363-367) - with a *range* that is
> triple that at around 54 mutations. By extrapolation, your stretch of
> 76 base pairs listed here should have an intrahuman average of 2 or so
> differences with a range of 6 differences. If the other species
> averaged out along these same lines, your numbers could be off by as
> much as 12 differences depending upon which individuals from each
> species group were compared. Actually though, the average range
> between humans is around 3.5% while chimps have a much higher average
> range of 15% and gorillas are even higher at 19%. This fairly wide
> range of potential gene pool variation shoots the statistical
> significance of your phylogenic trees all to bits - or so it seems to
> me.
This, once again, is talking about the hypervariable region of D-loop,
and is irrelevant to the genes I'm talking about.
> http://naturalselection.0catch.com/Files/dnamutationrates.html
> http://naturalselection.0catch.com/Files/earlyman.html
>
> In fact, some scientists, such as D. Melnick and G. Hoelzer (Columbia
> University), have tested the assumptions of mtDNA based phylogenic
> relationships and concluded: "Our results suggest serious problems
> with use of mtDNA to estimate "true" population genetic structure, to
> date cladogenic events, and in some cases, to construct phylogenies"
> (Melnick, D. and Hoelzer, G., 1992. What in the study of primate
> evolution is mtDNA good for? American Journal of Physical
> Anthropology, Supplement 14, p. 122.).
I'll have to look these papers up. In the meantime, allow me to
speculate. I don't know what Melnick and Hoelzer are talking about here,
but note "in some cases". That suggests they are not talking about any
general uselessness of mt sequences in phylogeny reconstruction, and so
their conclusion is probably irrelevant to the current case, unless you
can specifically relate it. Besides which, like I said you would get the
same result in this particular case from any gene, including any nuclear
gene.
> Likewise, Jonathan Marks (Yale
> University) declared mtDNA determined relationships to be highly
> biased: "Most analysis of mitochondrial DNA are so equivocal as to
> render a clear solution impossible, the preferred phylogeny relying
> critically on the choice of outgroup and clustering technique" (Marks,
> J., Chromosomal evolution in primates. The Cambridge Encyclopedia of
> Human Evolution, S. Jones, R. Martin, and D. Pilbeam (eds), Cambridge
> University Press, Cambridge, p. 302., 1992).
My suspicion here is that Marks was talking specifically about the
African ape trichotomy, which is indeed hard to resolve, and not just
hard for mt data. I purposely chose a node that's easy to resolve with
any data and by any method. (I'm also wondering why this sentence is in
an article that's supposedly about chromosomal evolution.)
> Further, an August 2002
> study of such phylogenetic trees used to analyse Neandertal sequences,
> by Gabriel Guitierrez et al., from the Universidad de Sevilla, Spain,
> was published in the well known journal, Molecular Biology and
> Evolution entitled, "A Reanalysis of the Ancient Mitochondrial DNA
> Sequences Recovered from Neandertal Bones." Consider their conclusions
> from the following abstract:
>
> "Recent reports analyzing mitochondrial DNA sequences from Neandertal
> bones have claimed that Neadnertals and modern humans are different
> species. The phylogenetic analyses carried out in these articles did
> not take into account the high substitution rate variation among sites
> observed in the human mitochondrial D-loop region and also lack an
> estimation of the parameters of the nucleotide substitution model. The
> separate phylogenic position of Neandertal-Human and Human-Human
> pairwise distance distributions overlap more than what previous
> studies suggested. We also show that the most ancient Neandertal HVI
> region is the most divergent when compared with modern human
> sequences. However, the opposite would be expected if the sequence had
> not been modified since the death of the specimen. Such incongruence
> is discussed in the light of diagenetic modifications in ancient DNA
> sequences."
Note that this conclusion is specifically about D-loop sequences and
ancient DNA sequences, neither of which is relevant to the data I am using.
All this is entirely irrelevant to the data I have presented. Why bring
it up at all?
> Guitierrez et al., went on to note that:
>
> "The main conclusion can be extracted from our analyses: the
> phylogenetic position of the ancient DNA sequences recovered from
> Neandertal bones is sensitive to the phylogenetic methods employed. It
> depends on the model of nucleotide substitution, the branch support
> method, and the set of data used. Adcock et al. (2001) recovered HVI
> sequences of archaic human bones from Australia, and their phylogenic
> analysis showed that two of the specimens were outgroups even for the
> most ancient African lineages. They concluded that this is evidence
> supporting the multiregional hypothesis. However, a second analysis
> carried out by Cooper et al. (2001) that took into account the
> heterogeneity of rates between sites and a large sample of modern
> humans, showed that both HVI sequences are located among extant
> humans. This case illustrates the influence of the nucleotide
> substitution model on the phylogenetic reconstruction of the human
> D-loop region. The NSG studies used poor parameter models of
> nucleotide substitution for their analysis, whereas we opted for
> complex (parameter rich) models following the likelihood ratio test...
> We believe that the likelihood mapping values supporting Neandertals
> as a different species might be artifactually increased."
Again, entirely irrelevant. Why did you do all this quoting?
> - Gutierrez, G., Sanchez, D., Marin, A. A Reanalysis of the
> Ancient Mitochondrial DNA Sequences Recovered from Neandertal Bones,
> Molecular Biology and Evolution, 19(8):1359-1366. 2002.
>
> - Krings, M., Stone, A., Schmitz, R.W., Krainitzki, H., Stoneking, M.
> and Pääbo, S., 1997. Neandertal DNA sequences and the origin of modern
> humans. Cell, 90:19-30.
>
> http://naturalselection.0catch.com/Files/earlyman.html
>
> Guitierrez also noted that depending upon the control region chosen,
> he could put a certain population of African humans as an outgroup
> with chimps and include Neandertals with modern humans. Certainly
> this is extremely politically incorrect, but that is the nature of
> using such mtDNA phylogenies that have no statistical validity beyond
> a few hundred generations at best.
Again, D-loop. My data have nothing to do with D-loop. It's irrelevant.
> So, to be honest, you must admit that your mtDNA phylogenetic
> comparison here has a few potential flaws of some significance. Given
> these potential problems, please do explain to me again the
> statistical relevance of your position . . .
All the objections you have raised are irrelevant to the data at hand.
They all relate (as far as I can tell) specifically to D-loop sequences,
ancient DNA, Neanderthals, or the Human-Gorilla-Chimp trichotomy. Not
one thing you have mentioned has anything to do with ND-3, ND-4, or the
existence of an African ape clade.
In other words, nothing you have said addresses the question I have
asked or the evidence I have presented. Didn't you notice that? If you
didn't, that says something about your ability to understand scientific
papers. If you did, it says something about your honesty.
Thanks for responding at all, but I would prefer a response that's
actually relevant to the questions I am asking. Could you try one of those?
Ron Okimoto
>
> Correct me if I am wrong, but the basic question here is, why do
> humans share more similar "nested" sequences with gorillas and chimps
> than with gibbons and orangutans if all of these differences are
> essentially neutral with regard to function? This is a most
> interesting question as it seems like there would be no reason for
> such nesting aside from differences in time from the most recent
> common ancestor. The question is, are these similarities and
> differences really all that statistically significant?
You are wrong. The nested changes do not have to be neutral for the
argument to work. The can be detrimental or selected for. If they
are selected for there is more chance of convergence that would mess
up the nesting. They are statistically significant, and we have a lot
more data than the set that John presents. The creationist used to be
fond of citing Yockey, but he made some estimate that the probability
that the nesting would occur just by chance instead of by common
descent was much lower than the probability that any polypeptide
assembled by chance.
>
> Your whole line of reasoning is especially interesting because, based
> on real-time studies of human mitochondrial mutation rates (from known
> historical families instead of assumed evolutionary scenarios), the
> average mutation rate for certain stretches of mtDNA runs about 2.5
> mutations/base pair/million years or 1 mutation in this 600bp sequence
> every 33 generations (660 years). What does this mean? It means
> something very interesting if the mutation rates for the sequences you
> are presenting here are similar to this rate of 2.5mut/bp/myr. I
> mean, when did the "most recent common ancestor" between all of these
> species live? If accurate, this mutation rate means that every single
> base pair in a stretch of mitochondrial DNA would have been
> mutated/changed at least *twice* in only one million years - making
> any phylogenetic analysis meaningless with regards to any sort of
> evolutionary relationship that is supposed to span something like 6 to
> 8 million years.
Sean this is really pathetic. Have you confirmed the Parson's paper
was not reproducible. I see that you have changed that page, but it
is still a dishonest use of the Parson's and Cann and Wilson paper.
Parson's was never verified and the Wilson's group paper was found to
be correct. Citing them anyother way is dishonest. Parson's paper is
equivalent to the first cold fusion paper. No one has been able to
reproduce this mutation rate in any data set since or before. I've
told you to look it up, but you want to remain ignorant. This is
dishonest. You are also talking about the noncoding hypervariable
region of the mitochondria and not the protein coding region. Do you
know what hypervariable means? Why do you persist in dishonestly
using the published literature after you have been informed of your
errors? Why bother to rewrite the page if you are still going to lie
about the data?
>
> Beyond this, you fail to list the intraspecies range of variation. I
> assume that the sequences you listed here either represent average
> sequences or the sequences of a single individual from each species.
> For example, for certain neutral sequences in mtDNA of around 600bp in
> length the *average* difference between humans is about 18 mutations
> (Genetics vol. 15, April 1997, pp. 363-367) - with a *range* that is
> triple that at around 54 mutations. By extrapolation, your stretch of
> 76 base pairs listed here should have an intrahuman average of 2 or so
> differences with a range of 6 differences. If the other species
> averaged out along these same lines, your numbers could be off by as
> much as 12 differences depending upon which individuals from each
> species group were compared. Actually though, the average range
> between humans is around 3.5% while chimps have a much higher average
> range of 15% and gorillas are even higher at 19%. This fairly wide
> range of potential gene pool variation shoots the statistical
> significance of your phylogenic trees all to bits - or so it seems to
> me.
Your example is again for the hypervariable region. For sequence like
the coding region it really doesn't matter that much. Taking the
random individual from a population you have a chance of picking the
odd one that would throw off your analysis, but the analysis isn't
very robust if it can't handle the random variation found within a
species. There usually isn't a problem here and if there were the
species would be so closely related that it would be hard to tell them
apart unless you used a lot of DNA sequence and it should all average
out. No one should use the hypervariable region of the mitochondria
to get an accurate picture of divergence between species. It can be
used to give you a rough idea of what the tree might look like, but
there are too many positions that have been hit multiple times even
between species as closely related as chimps and humans.
I wonder why chimps have 5 times the nuclear genetic diversity that
humans have if there were only two of them on the Ark? Why are their
mitochondria so different within their species compared to humans?
How long would it take to generate that diversity? Please don't use
the Parson's estimate again. You should never use it again until
someone verifies it, and that is unlikely because it has never been
verified, not even by Parson.
>
> http://naturalselection.0catch.com/Files/dnamutationrates.html
> http://naturalselection.0catch.com/Files/earlyman.html
>
> In fact, some scientists, such as D. Melnick and G. Hoelzer (Columbia
> University), have tested the assumptions of mtDNA based phylogenic
> relationships and concluded: "Our results suggest serious problems
> with use of mtDNA to estimate "true" population genetic structure, to
> date cladogenic events, and in some cases, to construct phylogenies"
> (Melnick, D. and Hoelzer, G., 1992. What in the study of primate
> evolution is mtDNA good for? American Journal of Physical
> Anthropology, Supplement 14, p. 122.). Likewise, Jonathan Marks (Yale
> University) declared mtDNA determined relationships to be highly
> biased: "Most analysis of mitochondrial DNA are so equivocal as to
> render a clear solution impossible, the preferred phylogeny relying
> critically on the choice of outgroup and clustering technique" (Marks,
> J., Chromosomal evolution in primates. The Cambridge Encyclopedia of
> Human Evolution, S. Jones, R. Martin, and D. Pilbeam (eds), Cambridge
> University Press, Cambridge, p. 302., 1992). Further, an August 2002
> study of such phylogenetic trees used to analyse Neandertal sequences,
> by Gabriel Guitierrez et al., from the Universidad de Sevilla, Spain,
> was published in the well known journal, Molecular Biology and
> Evolution entitled, "A Reanalysis of the Ancient Mitochondrial DNA
> Sequences Recovered from Neandertal Bones." Consider their conclusions
> from the following abstract:
All the problems are related to what sequence you use and what taxa
you are comparing. Closely related species have different problems
than distantly related species. You have to do it on a case by case
basis. These papers are only pointing out potential problems so other
scientists can make the most accurate estimates that they can. Look
at the data that John presented. I would contend that none of these
authors would have a problem with using this ape data to determine
phylogeny. They would have a big problem with it if we used mice as
the outgroup and tried to calculate times of divergence. The most
accurate outgroup would be a monkey, and not just one monkey, but
several that sample different branch lengths if at all possible. Most
studies only use one outgroup because it is good enough, but if the
outgroup is too distant, you can increase your accuracy by picking
taxa related to that outgroup to add to the analysis.
>
> "Recent reports analyzing mitochondrial DNA sequences from Neandertal
> bones have claimed that Neadnertals and modern humans are different
> species. The phylogenetic analyses carried out in these articles did
> not take into account the high substitution rate variation among sites
> observed in the human mitochondrial D-loop region and also lack an
> estimation of the parameters of the nucleotide substitution model. The
> separate phylogenic position of Neandertal-Human and Human-Human
> pairwise distance distributions overlap more than what previous
> studies suggested. We also show that the most ancient Neandertal HVI
> region is the most divergent when compared with modern human
> sequences. However, the opposite would be expected if the sequence had
> not been modified since the death of the specimen. Such incongruence
> is discussed in the light of diagenetic modifications in ancient DNA
> sequences."
>
> In the body of this paper, there were several other statements of
> interest:
This doesn't apply to extant species. They present evidence that some
of the changes are due to degredation of the DNA since the death of
the individual. This is no problem for extant species data, and we
aren't talking about species that diverged within the last million
years. The apes have diverged over a period up to 20 million years
for gibbons. The number of informative sites is much larger. We
don't seem to have your problem with this data set.
>
> "The NSG [The conclusions of Krings et al., based on their "Neandertal
> sequencing groups"] reported that the pairwise comparisons between the
> Neandertal and human sequences demonstrate that Neandertals are
> outside of modern human D-loop variability. In particular, Krings et
> al., (1997) stated that 'a total of 0.002% of the pairwise comparisons
> between human mtDNA sequences were larger than the smallest difference
> between the Neandertal and the humans.' We think that this point
> merits further analysis. The current database is biased because of the
> overrepresentation of some populations and the underrepresentation of
> others. For instance, the MOUSE database contains 6,012 entries for
> the HVI region, but 31% of the entries belong to only 20 populations
> out of 206 populations represented (10% of the total populations). The
> extreme cases are 306 Koreans, 126 Yaps, 120 Cayapa Amerindians, 119
> Mandeka, 115 Palau, and 100 white British. There are also 1,417
> entries of undetermined population (40% of them are from North America
> and 23% European, but only 9% are from Africa). Thus, African
> populations containing the most ancient lineages and the highest
> variation are underrepresented in the database.
Sean this is my prediction. The phylogenetic analysis indicates that
Neandertals do not branch with any extant human lineage. There is
extensive overlap in sites of substitution, but all the human
substitutions fall into known lineages. This just means that we can
tell that some lineages have just accumulated more mutations than
others. This is reflected in their branch lengths. We can tell this
because we have intermediate sequences for such lineages. This just
means that we can tell that all the modern human sequences are more
closely related to eachother than they are to the Neandertal sequences
even if some of them are more divergent from eachother than most human
sequences are from Neandertal.
Your bias data is a so what? If you were going to find Neandertal
mitochondrial sequences would you expect to find them in Europe where
they were last known to exist or in Africa? And what does the
Neandertal data have to do with the evidence for common descent
observed for the apes?
SNIP more irrelevant Neandertal ramblings:
Counter the data presented, and do it honestly instead of using your
known bogus arguments. I can't believe that you are still using the
Parson's paper and still misrepresenting the Cann and Wilson paper.
Ron Okimoto
>
> Sean
>
> www.naturalselection.0catch.com
Sean Pitman
> Sean Pitman wrote:
<snip>
> > Your whole line of reasoning is especially interesting because, based
> > on real-time studies of human mitochondrial mutation rates (from known
> > historical families instead of assumed evolutionary scenarios), the
> > average mutation rate for certain stretches of mtDNA runs about 2.5
> > mutations/base pair/million years or 1 mutation in this 600bp sequence
> > every 33 generations (660 years).
>
> The operative phrase here is "for certain stretches". You are talking
> about the hypervariable region of the D-loop. There's a reason it's
> called hypervariable. The mutation rate in that region is orders of
> magnitude higher than the mutation rate in, say, ND-3. So your whole
> discussion that relies on assuming this amazingly high rate is
> irrelevant to the question.
>
> (As a digression, let's assume your mutation rate is correct. That would
> be sufficient, as you state, to completely randomize all the sequences
> over a fairly short period of time. If so, then what's your explanation
> for the highly non-random pattern of similarities?)
So, since the D-loop region seems to have too many problems, perhaps
other mtDNA sequences that don't mutate so rapidly will work better?
Well, the reason why these other stretches of mtDNA, like the ND
regions, don't mutate as fast as the hypervariable D-loop regions is
that they code for functional proteins. This means that the ND4/ND5
sequences are limited in their mutation rate by natural selection -
which most certainly is a stabilizing force of nature. But, what about
their "neutral" differences?
In the January 2003 edition of the "Annals of Human Genetics",
geneticist Peter Forster of Cambridge published an article, "To Err is
Human", in which he noted that, "more than half of the mtDNA
sequencing studies ever published contain obvious errors." He then
asked: "Does it matter? Unfortunately, in many cases it does. . .
fundamental research papers, such as those claiming a recent African
origin for mankind (Cann, et al., 1987; Vigilant, et al., 1991) . . .
have been criticized, and rejected due to the extent of primary data
errors." Forster when on to note that this is "only the tip of the
iceberg. . . There is no reason to suppose that DNA sequencing errors
are restricted to mtDNA."
One month later, in the February 20, 2003 issue of "Nature", Carina
Dennis authored a commentary on Forster's work titled "Error Reports
Threaten to Unravel Databases of Mitochondrial DNA." Dennis reiterated
the findings that "more than half of all published studies of human
mitochondrial DNA (mtDNA) sequences contain mistakes." she went on to
note that, "The problem is far bigger than researchers had imagined.
The mistakes may be so extensive that geneticists could be drawing
incorrect conclusions to studies of human populations and evolution."
Also, the central dogma that mtDNA follows strict maternal inheritance
with only very rare paternal mtDNA "contamination" is being
challenged. Schwartz and Vissing noted in the August 2002 issue of
the New England Journal of Medicine that, "Mammalian mitochondrial DNA
(mtDNA) is thought to be strictly maternally inherited. . . Very small
amounts of paternally inherited mtDNA have been detected by the
polymerase chain reaction (PCR) in mice after several generations of
interspecific backcrosses. . . We report the case of a 28-year-old man
with mitochondrial myopathy due to a novel 2-bp mtDNA deletion. . . We
determined that the mtDNA harboring the mutation was paternal in
origin and accounted for 90 percent of the patient's muscle mtDNA." Of
course, "If mtDNA can recombine, irrespective of the mechanism, there
are important implications for mtDNA evolution and for phylogenetic
studies that use mtDNA" (Morris, Andrew A. M., and Robert N.
Lightowlers (2000), "Can Paternal mtDNA be Inherited?", The Lancet,
355:1290-1291, April 15).
Now, you claim that out of 694 nucleotides in the DN4/DN5 regions that
only 76 of them have "informative differences". Of these, 18 are
involved in a change in amino acid composition leaving only 58 as
clearly neutral differences (discussed further below). This is only 8%
of the total number of sequences. Of these 58, humans share only 12
or so more differences with chimps than with orangutans and gibbons.
Also added into this mix is a 1 or so amino acid variation among
individuals within these species in these particular coding regions of
mtDNA. This leaves only around 10 or so differences to base your
clusters on. This is only around 1.5% of the total sequence length
and only 17% of the neutral sequences. Do you think, in the light of
just a few of the problems listed above for mtDNA sequence analysis,
that a 17% increased nesting with chimps, humans, and gorillas over
gibbons and orangutans is really all that significant - especially
since this is only 1.5% of the total sequence length? Also, these 58
neutral loci, with their 10 or so clustered differences in the listed
species, if truly neutral, are no less susceptible to mutational hits
than are the sequences found in the D-loop region. Therefore, their
rate of mutation should also be equivalent to the rate of mutation
found in the D-loop region (which even you admit to being at least one
order of magnitude higher than is recognized in coding regions of
mtDNA). If there is a difference found in the rate of mutation between
these different regions, even with respect to "neutral" changes, what
is the explanation for this phenomenon? Perhaps even these mutations
aren't really neutral? Of course, this just screws up everything now
doesn't it?
The fact of the matter is, even in mtDNA regions such as the ND4/ND5
regions, "Silent [neutral] sites saturate extremely quickly,
presumably owing to the substitution bias and, perhaps, to an
accelerated mutation rate. Results emphasize the importance of using
only the most closely related sequences in order to infer patterns of
substitution accurately for nematodes or for other taxa having
strongly composition-biased DNA. ND4 also shows high amino acid
polymorphism at both the intra-and interspecific levels, and in higher
level comparisons, there is evidence of saturation at variable amino
acid sites. In general, we recommend using mtDNA coding genes only for
phylogenetics of relatively closely related nematode species and, even
then, using only nonsynonymous substitutions and the more conserved
mitochondrial genes (e.g., cytochrome oxidases). On the other hand,
the high substitution rate in genes such as ND4 should make them
excellent for population genetics studies, identifying cryptic
species, and resolving relationships among closely related congeners
when other markers show insufficient variation" (Michael S. Blouin,
Charles A. Yowell, Charles H. Courtney, and John B. Dame,
"Substitution Bias, Rapid Saturation, and the Use of mtDNA for
Nematode Systematics", Department of Zoology, Oregon State University;
and Department of Pathobiology, University of Florida, 1998).
This kinda messes up your ND4 hypothesis - doesn't it? Are primate
ND4 sequences all that different from nematode mtDNA ND4 sequences in
structure and function? If not, then why do these ND4 sequences in
nematodes mutate so fast and have so many polymorphisms? Why do the
neutral sites in the ND4 sequence saturate so quickly?
Also, your proposed clustering effect might even be less significant
than it already seems once you add in the transition/transversion rate
bias and codon frequency biases into the picture. Consider an
abstract from a paper by Yang and Nielsen published in the 1998 issue
of the "Journal of Molecular Evolution" (Even though it is discussion
nDNA, the implications for mtDNA are still clear):
"A maximum likelihood approach was used to estimate the synonymous and
nonsynonymous substitution rates in 48 nuclear genes from primates,
artiodactyls, and rodents. A codon-substitution model was assumed,
which accounts for the genetic code structure, transition/transversion
bias, and base frequency biases at codon positions. Likelihood ratio
tests were applied to test the constancy of nonsynonymous to
synonymous rate ratios among branches (evolutionary lineages). It is
found that at 22 of the 48 nuclear loci examined, the
nonsynonymous/synonymous rate ratio varies significantly across
branches of the tree. The result provides strong evidence against a
strictly neutral model of molecular evolution. Our likelihood
estimates of synonymous and nonsynonymous rates differ considerably
from previous results obtained from approximate pairwise sequence
comparisons. The differences between the methods are explored by
detailed analyses of data from several genes. Transition/transversion
rate bias and codon frequency biases are found to have significant
effects on the estimation of synonymous and nonsynonymous rates, and
approximate methods do not adequately account for those factors. The
likelihood approach is preferable, even for pairwise sequence
comparison, because more realistic models about the mutation and
substitution processes can be incorporated in the analysis" (Yang Z,
Nielsen R. "Synonymous and nonsynonymous rate variation in nuclear
genes of mammals", J Mol Evol. 1998 Apr;46(4):409-18).
In this line, Bielawskia et. al., published a paper in the November
2000 issue of "Genetics" noting that, "Previous studies of mammalian
nuclear genes largely employed approximate methods to estimate rates
of nonsynonymous and synonymous substitutions. Because these methods
did not account for major features of DNA sequence evolution such as
transition/transversion rate bias and unequal codon usage, they might
not have produced reliable results. To evaluate the impact of the
estimation method, we analyzed a sample of 82 nuclear genes from the
mammalian orders Artiodactyla, Primates, and Rodentia using both
approximate and maximum-likelihood methods. Maximum-likelihood
analysis indicated that synonymous substitution rates were positively
correlated with GC content at the third codon positions, but
independent of nonsynonymous substitution rates. Approximate methods,
however, indicated that synonymous substitution rates were independent
of GC content at the third codon positions, but were positively
correlated with nonsynonymous rates. Failure to properly account for
transition/transversion rate bias and unequal codon usage appears to
have caused substantial biases in approximate estimates of
substitution rates" (Joseph P. Bielawskia, Katherine A. Dunna, and
Ziheng Yanga, "Rates of Nucleotide Substitution and Mammalian Nuclear
Gene Evolution: Approximate and Maximum-Likelihood Methods Lead to
Different Conclusions", Genetics, Vol. 156, 1299-1308, November 2000).
There are several very interesting things to notice here. Note that
"the nonsynonymous/synonymous rate ratio varies significantly across
branches of the tree [of life]. The result provides strong evidence
against a strictly neutral model of molecular evolution." What is
especially interesting in this analysis is that the
transition/transversion rate bias and codon frequency biases have a
"significant" effect on the estimation of the synonymous and
nonsynonymous rates and that these biases have not been adequately
accounted for! In fact, this bias is described as substantially
affecting the estimates of substitution rates. Basically, depending
upon which method you choose, you will come to different phylogenetic
conclusions because of this bias problem.
Now, don't you think that this same transition/transversion rate bias
problem also affects mtDNA sequence analysis? Is it even possible to
correct for this substitution rate bias problem in a non-biased way -
especially with those differences that are actually functional?
Also consider that the 18 mutations that resulted in a change in amino
acid sequence might not be as neutral as you have surmised. It seems
that, "Human mtDNA shows striking regional variation, traditionally
attributed to genetic drift. However, it is not easy to account for
the fact that only two mtDNA lineages (M and N) left Africa to
colonize Eurasia and that lineages A, C, D, and G show a 5-fold
enrichment from central Asia to Siberia. As an alternative to drift,
natural selection might have enriched for certain mtDNA lineages as
people migrated north into colder climates. To test this hypothesis we
analyzed 104 complete mtDNA sequences from all global regions and
lineages. African mtDNA variation did not significantly deviate from
the standard neutral model, but European, Asian, and Siberian plus
Native American variations did. Analysis of amino acid substitution
mutations (nonsynonymous, Ka) versus neutral mutations (synonymous,
Ks) (kaks) for all 13 mtDNA protein-coding genes revealed that the
ATP6 gene had the highest amino acid sequence variation of any human
mtDNA gene, even though ATP6 is one of the more conserved mtDNA
proteins. Comparison of the kaks ratios for each mtDNA gene from the
tropical, temperate, and arctic zones revealed that ATP6 was highly
variable in the mtDNAs from the arctic zone, cytochrome b was
particularly variable in the temperate zone, and cytochrome oxidase I
was notably more variable in the tropics. Moreover, multiple amino
acid changes found in ATP6, cytochrome b, and cytochrome oxidase I
appeared to be functionally significant. From these analyses we
conclude that selection may have played a role in shaping human
regional mtDNA variation and that one of the selective influences was
climate" (Mishmar D et. al., "Natural selection shaped regional mtDNA
variation in humans" Proc Natl Acad Sci U S A. 2003 Jan
7;100(1):171-6. Epub 2002 Dec 30).
http://www.ncbi.nlm.nih.gov/entrez/query.fcgidb=PubMed&cmd=Retrieve&dopt=Citation&list_uids=12509511
http://www.apologeticspress.org/inthenews/2003/itn-03-03.htm
http://oregonstate.edu/~blouinm/pdf_files/MBE1998.pdf
Sean
John Harshman
Sean Pitman wrote:
The rate of fixation (and assuming neutrality, of mutation) in silent
sites of coding regions in mtDNA is much, much less than the rate in the
hypervariable region, assuming that measure you quote actually is
correct. You may if you like suppose that this is evidence for the
silent sites not evolving neutrally. (Though I think it actually records
a higher mutation rate.) But whatever, they don't change at such a rate
as to randomize the sequences and render phylogenetic analyses impossible.
> In the January 2003 edition of the "Annals of Human Genetics",
> geneticist Peter Forster of Cambridge published an article, "To Err is
> Human", in which he noted that, "more than half of the mtDNA
> sequencing studies ever published contain obvious errors." He then
> asked: "Does it matter? Unfortunately, in many cases it does. . .
> fundamental research papers, such as those claiming a recent African
> origin for mankind (Cann, et al., 1987; Vigilant, et al., 1991) . . .
> have been criticized, and rejected due to the extent of primary data
> errors." Forster when on to note that this is "only the tip of the
> iceberg. . . There is no reason to suppose that DNA sequencing errors
> are restricted to mtDNA."
Your point? Are you claiming that because some studies have errors, then
all studies must be invalid? Are you claiming that the sequence I have
presented has errors that particularly invalidate the phylogeny? If so,
how do you account for the fact that any other locus I cared to choose
would give me the same results?
> One month later, in the February 20, 2003 issue of "Nature", Carina
> Dennis authored a commentary on Forster's work titled "Error Reports
> Threaten to Unravel Databases of Mitochondrial DNA." Dennis reiterated
> the findings that "more than half of all published studies of human
> mitochondrial DNA (mtDNA) sequences contain mistakes." she went on to
> note that, "The problem is far bigger than researchers had imagined.
> The mistakes may be so extensive that geneticists could be drawing
> incorrect conclusions to studies of human populations and evolution."
Since the question at hand has nothing to do with studies of human
populations, why bring that up?
> Also, the central dogma that mtDNA follows strict maternal inheritance
> with only very rare paternal mtDNA "contamination" is being
> challenged.
So? If paternal contamination happens every so often (or even
frequently), how does that effect estimates of phylogeny? I'll tell you:
not at all. Notice: nice, biparentally inherited nuclear genes give us
the same tree. Why are you continuing to throw all these irrelevancies
at me?
> Schwartz and Vissing noted in the August 2002 issue of
> the New England Journal of Medicine that, "Mammalian mitochondrial DNA
> (mtDNA) is thought to be strictly maternally inherited. . . Very small
> amounts of paternally inherited mtDNA have been detected by the
> polymerase chain reaction (PCR) in mice after several generations of
> interspecific backcrosses. . . We report the case of a 28-year-old man
> with mitochondrial myopathy due to a novel 2-bp mtDNA deletion. . . We
> determined that the mtDNA harboring the mutation was paternal in
> origin and accounted for 90 percent of the patient's muscle mtDNA." Of
> course, "If mtDNA can recombine, irrespective of the mechanism, there
> are important implications for mtDNA evolution and for phylogenetic
> studies that use mtDNA" (Morris, Andrew A. M., and Robert N.
> Lightowlers (2000), "Can Paternal mtDNA be Inherited?", The Lancet,
> 355:1290-1291, April 15).
>
> Now, you claim that out of 694 nucleotides in the DN4/DN5 regions that
> only 76 of them have "informative differences". Of these, 18 are
> involved in a change in amino acid composition leaving only 58 as
> clearly neutral differences (discussed further below). This is only 8%
> of the total number of sequences. Of these 58, humans share only 12
> or so more differences with chimps than with orangutans and gibbons.
That's not true. Your math is wrong. In fact I don't have the data at
hand to divide the non-synonymous changes among topologies, but let's
assume they are more or less evenly spread. This means 58/76 * 24 = 18
sites support the "true" tree, while the best supported of the two
"wrong" trees you mention has 58/76 * 4 = 3, for a difference of 15. By
the way, on what basis did you eliminate the amino acid changes from
consideration?
> Also added into this mix is a 1 or so amino acid variation among
> individuals within these species in these particular coding regions of
> mtDNA.
Not that I'm doubting you, but can you back that one up? Even if true,
it only introduces random error, and is just as likely to support one
tree as another.
> This leaves only around 10 or so differences to base your
> clusters on.
Again, interesting math. 12 - 1 = 10?
> This is only around 1.5% of the total sequence length
> and only 17% of the neutral sequences. Do you think, in the light of
> just a few of the problems listed above for mtDNA sequence analysis,
> that a 17% increased nesting with chimps, humans, and gorillas over
> gibbons and orangutans is really all that significant - especially
> since this is only 1.5% of the total sequence length?
Yes, I do. What makes you think it isn't? Any valid statistical test
would find this difference highly significant. Feel free to try one.
Chance is just not a credible explanation.
> Also, these 58
> neutral loci,
Point of terminology: a locus is, more or less, a gene. What you have
here are sites.
> with their 10 or so clustered differences in the listed
> species, if truly neutral, are no less susceptible to mutational hits
> than are the sequences found in the D-loop region. Therefore, their
> rate of mutation should also be equivalent to the rate of mutation
> found in the D-loop region (which even you admit to being at least one
> order of magnitude higher than is recognized in coding regions of
> mtDNA). If there is a difference found in the rate of mutation between
> these different regions, even with respect to "neutral" changes, what
> is the explanation for this phenomenon? Perhaps even these mutations
> aren't really neutral? Of course, this just screws up everything now
> doesn't it?
No. Why should it? Please explain how all this conspires to produce a
false phylogenetic result.
> The fact of the matter is, even in mtDNA regions such as the ND4/ND5
> regions, "Silent [neutral] sites saturate extremely quickly,
> presumably owing to the substitution bias and, perhaps, to an
> accelerated mutation rate. Results emphasize the importance of using
> only the most closely related sequences in order to infer patterns of
> substitution accurately for nematodes or for other taxa having
> strongly composition-biased DNA. ND4 also shows high amino acid
> polymorphism at both the intra-and interspecific levels, and in higher
> level comparisons, there is evidence of saturation at variable amino
> acid sites. In general, we recommend using mtDNA coding genes only for
> phylogenetics of relatively closely related nematode species and, even
> then, using only nonsynonymous substitutions and the more conserved
> mitochondrial genes (e.g., cytochrome oxidases). On the other hand,
> the high substitution rate in genes such as ND4 should make them
> excellent for population genetics studies, identifying cryptic
> species, and resolving relationships among closely related congeners
> when other markers show insufficient variation" (Michael S. Blouin,
> Charles A. Yowell, Charles H. Courtney, and John B. Dame,
> "Substitution Bias, Rapid Saturation, and the Use of mtDNA for
> Nematode Systematics", Department of Zoology, Oregon State University;
> and Department of Pathobiology, University of Florida, 1998).
It may surprise you to learn that different taxa evolve at different
rates, and that ideas of "closely related" also vary. Nematodes and
primates are quite different in terms of mtDNA evolution. Silent sites
are not saturated within primates, and this is easy to show. One simple
way to show it is just by observing the low levels of detected homoplasy
on that tree. Again, you are resorting to irrelevancies and are not
addressing the actual data.
> This kinda messes up your ND4 hypothesis - doesn't it? Are primate
> ND4 sequences all that different from nematode mtDNA ND4 sequences in
> structure and function? If not, then why do these ND4 sequences in
> nematodes mutate so fast and have so many polymorphisms? Why do the
> neutral sites in the ND4 sequence saturate so quickly?
I suspect this may have something to do with the much greater
evolutionary rates among nematodes. Some of this is probably the effect
of very short generation times, but nematodes are notorious for having
unusually long branches on lots of trees, so there may be something else
working there too. But again, irrelevant to primate evolution.
> Also, your proposed clustering effect might even be less significant
> than it already seems once you add in the transition/transversion rate
> bias and codon frequency biases into the picture.
No, as it happens, more complex evolutionary models that take these
factors into account will still give you the same tree from these data,
as I would expect considering the low actual numbers of changes. With
short enough branches, the model you pick doesn't really matter.
> Consider an
> abstract from a paper by Yang and Nielsen published in the 1998 issue
> of the "Journal of Molecular Evolution" (Even though it is discussion
> nDNA, the implications for mtDNA are still clear):
>
> "A maximum likelihood approach was used to estimate the synonymous and
> nonsynonymous substitution rates in 48 nuclear genes from primates,
> artiodactyls, and rodents. A codon-substitution model was assumed,
> which accounts for the genetic code structure, transition/transversion
> bias, and base frequency biases at codon positions. Likelihood ratio
> tests were applied to test the constancy of nonsynonymous to
> synonymous rate ratios among branches (evolutionary lineages). It is
> found that at 22 of the 48 nuclear loci examined, the
> nonsynonymous/synonymous rate ratio varies significantly across
> branches of the tree. The result provides strong evidence against a
> strictly neutral model of molecular evolution.
Well, duh.
> Our likelihood
> estimates of synonymous and nonsynonymous rates differ considerably
> from previous results obtained from approximate pairwise sequence
> comparisons. The differences between the methods are explored by
> detailed analyses of data from several genes. Transition/transversion
> rate bias and codon frequency biases are found to have significant
> effects on the estimation of synonymous and nonsynonymous rates, and
> approximate methods do not adequately account for those factors. The
> likelihood approach is preferable, even for pairwise sequence
> comparison, because more realistic models about the mutation and
> substitution processes can be incorporated in the analysis" (Yang Z,
> Nielsen R. "Synonymous and nonsynonymous rate variation in nuclear
> genes of mammals", J Mol Evol. 1998 Apr;46(4):409-18).
Again, what does this have to do with addressing the question at hand?
You are just throwing more irrelevancies at me.
> In this line, Bielawskia et. al., published a paper in the November
> 2000 issue of "Genetics" noting that, "Previous studies of mammalian
> nuclear genes largely employed approximate methods to estimate rates
> of nonsynonymous and synonymous substitutions. Because these methods
> did not account for major features of DNA sequence evolution such as
> transition/transversion rate bias and unequal codon usage, they might
> not have produced reliable results. To evaluate the impact of the
> estimation method, we analyzed a sample of 82 nuclear genes from the
> mammalian orders Artiodactyla, Primates, and Rodentia using both
> approximate and maximum-likelihood methods. Maximum-likelihood
> analysis indicated that synonymous substitution rates were positively
> correlated with GC content at the third codon positions, but
> independent of nonsynonymous substitution rates. Approximate methods,
> however, indicated that synonymous substitution rates were independent
> of GC content at the third codon positions, but were positively
> correlated with nonsynonymous rates. Failure to properly account for
> transition/transversion rate bias and unequal codon usage appears to
> have caused substantial biases in approximate estimates of
> substitution rates" (Joseph P. Bielawskia, Katherine A. Dunna, and
> Ziheng Yanga, "Rates of Nucleotide Substitution and Mammalian Nuclear
> Gene Evolution: Approximate and Maximum-Likelihood Methods Lead to
> Different Conclusions", Genetics, Vol. 156, 1299-1308, November 2000).
Again, you will have to explain how this is relevant to the data at hand.
> There are several very interesting things to notice here. Note that
> "the nonsynonymous/synonymous rate ratio varies significantly across
> branches of the tree [of life]. The result provides strong evidence
> against a strictly neutral model of molecular evolution."
Who was proposing a strictly neutral model of molecular evolution?
Selection is the reason for a difference between synonymous and
non-synonymous rates in the first place. How is this relevant?
> What is
> especially interesting in this analysis is that the
> transition/transversion rate bias and codon frequency biases have a
> "significant" effect on the estimation of the synonymous and
> nonsynonymous rates and that these biases have not been adequately
> accounted for!
So?
> In fact, this bias is described as substantially
> affecting the estimates of substitution rates. Basically, depending
> upon which method you choose, you will come to different phylogenetic
> conclusions because of this bias problem.
No, you mistake two different things. Estimates of substitution rates
can be wrong without affecting phylogenetic conclusions. And in fact any
method will give you the same tree with the ND4/5 data.
> Now, don't you think that this same transition/transversion rate bias
> problem also affects mtDNA sequence analysis? Is it even possible to
> correct for this substitution rate bias problem in a non-biased way -
> especially with those differences that are actually functional?
You mistake this too. Very few of the differences are in fact
functional. And there are indeed methods that account for
transition/transversion rate differences. If you apply those methods,
you get the same tree in the present case.
> Also consider that the 18 mutations that resulted in a change in amino
> acid sequence might not be as neutral as you have surmised.
I'm not surmising that they are neutral. (Though many of them likely
are, especially the relatively common changes to acids of similar
characteristics.)
That's way cool. Thanks for the citation. But how is this at all
relevant to the present case?
> http://www.ncbi.nlm.nih.gov/entrez/query.fcgidb=PubMed&cmd=Retrieve&dopt=Citation&list_uids=12509511
>
> http://www.apologeticspress.org/inthenews/2003/itn-03-03.htm
>
> http://oregonstate.edu/~blouinm/pdf_files/MBE1998.pdf
Okay, this seems to be the pattern here. You throw a bunch of irrelevant
references at me, I dispose of them, and then without commenting further
on those you throw another batch of irrelevant references. I suppose
this could go on forever, but why?
So far you have made exactly zero attempts to account for the patterns
in the ND4/5 data. I'm asking you how you can explain them in any way
other than phylogeny, and you haven't responded. Why?
Ron Okimoto
SNIP:
I'll just butt in here because I sequenced the first nematode
mitochondrial DNAs and did the first analysis on them. Nematode
mitochondrial DNAs are very different in sequence than primate
mitochondrial DNAs. They have extreme base bias. The C. elegans
mtDNA is around 80% AT. Third positions don't just saturate at a high
rate, but third positions are nearly always A or T. You would be
crazy to use these positions in any phylogenetic analysis. The third
positions not only change more rapidly, but you are basically reduced
from four possible states to only two. Primates do not have this
extreme of a problem. Just compare the sequence of the human mtDNA to
C. elegans.
SNIP:
>
> > In this line, Bielawskia et. al., published a paper in the November
> > 2000 issue of "Genetics" noting that, "Previous studies of mammalian
> > nuclear genes largely employed approximate methods to estimate rates
> > of nonsynonymous and synonymous substitutions. Because these methods
> > did not account for major features of DNA sequence evolution such as
> > transition/transversion rate bias and unequal codon usage, they might
> > not have produced reliable results. To evaluate the impact of the
> > estimation method, we analyzed a sample of 82 nuclear genes from the
> > mammalian orders Artiodactyla, Primates, and Rodentia using both
> > approximate and maximum-likelihood methods. Maximum-likelihood
> > analysis indicated that synonymous substitution rates were positively
> > correlated with GC content at the third codon positions, but
> > independent of nonsynonymous substitution rates. Approximate methods,
> > however, indicated that synonymous substitution rates were independent
> > of GC content at the third codon positions, but were positively
> > correlated with nonsynonymous rates. Failure to properly account for
> > transition/transversion rate bias and unequal codon usage appears to
> > have caused substantial biases in approximate estimates of
> > substitution rates" (Joseph P. Bielawskia, Katherine A. Dunna, and
> > Ziheng Yanga, "Rates of Nucleotide Substitution and Mammalian Nuclear
> > Gene Evolution: Approximate and Maximum-Likelihood Methods Lead to
> > Different Conclusions", Genetics, Vol. 156, 1299-1308, November 2000).
>
>
> Again, you will have to explain how this is relevant to the data at hand.
It would make the taxa look more similar than the data indicates, so
Sean loses on this one too. It would collapse your branch lengths and
you expect that your taxa are more divergent than they appear to be.
In short if this wasn't happening the data would look even better for
common descent.
Ron Okimoto
SNIP:
John Harshman
Ron Okimoto wrote:
If I recall, they also have problems with nuclear genes too. I don't pay
attention enough to know if this too is AT bias. C. elegans at least
seems to have a very compressed genome. I would expect composition of
nuclear genes to vary quite a bit over the genome anyway.
Do you think he will ever stop throwing irrelevant references and start
addressing the actual issues?
Ron Okimoto
The nuclear gene problem is not AT bias. It is long branch length
problems. For some reason things like flatworms and nematodes evolve
more rapidly than other metazoans. The nuclear rRNA genes have
changed so much that it is difficult to compare them to other
metazoans. I wrote a paper about the mitochondrial rRNAs and we tried
to determine why nematodes were not branching as expected using the
nuclear data. The incorrect branching seemed to be due to the use of
sequences comparisons based more on fantasy than reality. There was
no way to match up those sequences. They were essentially trying to
get a phylogeny out of random associations. So much sequence change
had occurred in the genes that you couldn't really tell what matched
with what.
I don't know why nematodes seem to be evolving more rapidly. They are
among the simplest metazoans and selection constraints may not be as
high as in other metazoans, or they may have evolved long before we
think.
If he did he would soon have nothing to address.
Ron Okimoto
John Harshman
Ron Okimoto wrote:
> John Harshman <jharshman....@pacbell.net> wrote in message news:<3F9014DE...@pacbell.net>...
>
>>Ron Okimoto wrote:
>>
>>
>>>John Harshman <jharshman....@pacbell.net> wrote in message news:<3F8F34DE...@pacbell.net>...
[snippy snip snip]
Given the evidence for Ecdysozoa (much of it non-genetic), the latter
answer seems unlikely. I wonder if there's something about secondary
simplification (which seems to be the case here) that causes some kind
of genomic revolution. Haven't they lost a lot of genes too? That might
radically alter the selective environment of the remaining genes. All
speculation. What you really need is to sequence some region from lots
and lots of nematode species. Is there any major effort for nematode
phylogeny?
[and snip]
Dunno
BTW, where'd he go?
John Harshman
Dunno wrote:
Give him some credit. He came in for two rounds, and perhaps he will try
again later. Of course, all he did was try to snow us with irrelevant
but impressive-sounding quote mining, but that's something.
And his current position seems to be that humans might be apes or might
not, but there just isn't enough evidence yet either way. So his
argument with Behe wouldn't be over issues of common descent, but over
the sufficiency of the data to show common descent. I'd love to see that
argument if only it could be arranged.
Ron Okimoto
John Harshman wrote:
> Dunno wrote:
>
> > In article <38c5d0dd.0310...@posting.google.com>, Frank J wrote:
> >
> >>"R. Dunno" <muen...@hushmail.com> wrote in message news:<slrnbok078....@old486-20.hushmail.com>...
> >>
> SNIP:
>
> >>Michael Behe, whom Sean raved about, admitted that chimps and humans
> >>share common ancestors, and thus saw no need to propose a recent
> >>abiogenesis of one or more eukaryotes, much less a theory for it. One
> >>then would expect Sean to challenge Behe directly on this point. In
> >>fact, given that Behe does not have "a prior commitment to naturalism"
> >>one would expect Sean to consider Behe a more reasonable opponent than
> >>us "dogmatic disciples of Darwin."
> >>
> >>
> >
> > BTW, where'd he go?
>
> Give him some credit. He came in for two rounds, and perhaps he will try
> again later. Of course, all he did was try to snow us with irrelevant
> but impressive-sounding quote mining, but that's something.
>
> And his current position seems to be that humans might be apes or might
> not, but there just isn't enough evidence yet either way. So his
> argument with Behe wouldn't be over issues of common descent, but over
> the sufficiency of the data to show common descent. I'd love to see that
> argument if only it could be arranged.
Nesting, you have to get him to understand the significance of the nested data.
This will probably be impossible.
Ron Okimoto
John Harshman
Ron Okimoto wrote:
Let's try a statistical test and see if that makes any difference. Let's
suppose, as our null hypothesis, that the sequences are randomized with
respect to phylogeny (perhaps because there is no phylogeny) and that
apparent support for African apes is merely a chance fluctuation. And
let's try a chi-square test. Here it is:
These are all the possible hypotheses of relationship, and the observed
number of sites supporting them. Expected values would be equal, or the
sum/7. There are 6 degrees of freedom, and the sum of squares is 57.8.
P, or the probability of this amount of asymmetry in the distribution
arising by chance, is very low. When I tried it in Excel, I got
P=1.25*10^-10, or 0.000000000125. Might as well call that zero, I think.
hypothesis obs. exp.
African apes (+) 24 6.43
gibbon+gorilla (1) 6 6.43
orangutan+gorilla (2) 4 6.43
gibbon+human (3) 4 6.43
gibbon+chimp (4) 3 6.43
orangutan+human (5) 2 6.43
orangutan+chimp (6) 2 6.43
sum 45 45
So, Sean. The difference is significant. Now the question is how you
account for it. I account for it by supposing that the null hypothesis
is just plain wrong, and that there is a phylogeny, and that the
phylogeny involves the African apes, including Homo, being related by a
common ancestor more recent than their common ancestor with orangutans
or gibbons. How about you?
R. Dunno
Hope so. Neat subject matter.