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Angela
16-09-15, 17:29
The admixture was on balance disadvantageous and we've been purifying our genome of those alleles ever since.The lingering load of archaic admixture in modern human populations.

Authors:
K. Harris1,2 ; R. Nielsen2,3

Institutes
1) Stanford University, Stanford, CA; 2) University of California Berkeley, Berkeley, CA; 3) Center for Bioinformatics, University of Copenhagen, Copenhagen, Denmark.
Abstract:

"Founder effects and bottlenecks can damage fitness by letting deleterious alleles drift to high frequencies. This almost certainly imposed a burden on Neanderthals and Denisovans, archaic hominid populations whose genetic diversity was less than a quarter of the level seen in humans today. A more controversial question is whether the out-of-Africa bottleneck created differences in genetic load between modern human populations. Some previous studies concluded that this bottleneck saddled non-Africans with potentially damaging genetic variants that could affect disease incidence across the globe today (e.g. Lohmueller, et al. 2009; Fu, et al. 2014), while other studies have concluded that there is little difference in genetic load between Africans and non-Africans (e.g. Simons, et al. 2014; Do, et al. 2015). Although previous studies have devoted considerable attention to simulating the accumulation of deleterious mutations during the out-of-Africa bottleneck, none to our knowledge have incorporated the fitness effects of introgression from Neanderthals into non-Africans. We present simulations showing that archaic introgression may have had a greater fitness effect than the out-of-Africa bottleneck itself, saddling non-Africans with weakly deleterious alleles that accumulated as nearly neutral variants in Neanderthals. Assuming that the exome experiences deleterious mutations with additive fitness effects drawn from a previously inferred gamma distribution, we predict that the fitness of the average Neanderthal was about 50% lower than the fitness of the average human, implying the existence of strong selection against early Neanderthal-human hybrids. This is a direct consequence of mutation accumulation during a period of low Neanderthal population size that is thought to have lasted ten times longer than the out-of-Africa bottleneck (Pruefer, et al. 2014). Although our model predicts some transmission of deleterious Neanderthal variation to present-day non-Africans, it also predicts that many Neanderthal alleles have been purged away, depleting conserved genomic regions of Neanderthal ancestry as observed empirically by Sankararaman, et al. (2014). Our results imply that the deficit of Neanderthal DNA from functional genomic regions can be explained without the action of epistatic reproductive incompatibilities between human and Neanderthal alleles.

Tomenable
16-09-15, 19:41
Admixtures in Non-Africans is one thing, but there were also archaic admixtures in Africa from local hominins.

Angela
16-09-15, 22:56
Admixtures in Non-Africans is one thing, but there were also archaic admixtures in Africa from local hominins.

Well, Neanderthals were also more archaic.

Anyway, the point is that they weren't very genetically fit, basically due to founder effects and bottlenecks (again).

One of my friends on here accused me of being prejudiced against Neanderthals??!! I, of course, vehemently denied it!

I just thought that's what the papers were showing, i.e. that the admixture wasn't advantageous to us and we've been purging their genes ever since. This one is just another in the list saying basically the same thing.

LeBrok
17-09-15, 03:52
Well, Neanderthals were also more archaic.

Anyway, the point is that they weren't very genetically fit, basically due to founder effects and bottlenecks (again).

One of my friends on here accused me of being prejudiced against Neanderthals??!! I, of course, vehemently denied it!

I just thought that's what the papers were showing, i.e. that the admixture wasn't advantageous to us and we've been purging their genes ever since. This one is just another in the list saying basically the same thing.
Did they say in what way we are purging our genome? New mutations or borrowing the "fit" segments again from Africans?

It all should mean that Mesolithic Hunter Gatherers should have had way more Neanderthal genome, 10%, 20%, 30%?. They were true hybrids back then, as we have just leftovers left.

bicicleur
17-09-15, 08:42
look at the Y DNA pedigree, haplogroup BT is 126000 year old

http://www.yfull.com/tree/BT/

it generated just 5 branches, B , C , D , E , F

B split to Africa

C,D,E,F all stayed in isolation till their expansion times +/- 50.000 years ago

that is a 75000 year bottleneck

how did they stay genetically fit?

55-60.000 years ago they would have admixed with Neanderthals (well, C,D,F, not E)

bicicleur
17-09-15, 08:48
Admixtures in Non-Africans is one thing, but there were also archaic admixtures in Africa from local hominins.

there were bottlenecks in Africa too

that is why only haplogroup A survived and more archaic hominins went extinct

it is estimated that the last admixture between haplogroup A and archaic African hominins happened 40.000 years ago

Greying Wanderer
17-09-15, 10:38
so the consensus is moving from low levels of recent neanderthals admixture to high levels but deleterious?

that makes more sense than sudden instant extinction at least.

bicicleur
17-09-15, 11:08
so the consensus is moving from low levels of recent neanderthals admixture to high levels but deleterious?

that makes more sense than sudden instant extinction at least.


Oase 1[edit (https://en.wikipedia.org/w/index.php?title=Pe%C8%99tera_cu_Oase&action=edit&section=2)]Against this background, particularly noteworthy is the fact that "Oase 1" exhibits morphological traits combining a variety of archaic Homo, derived early modern human, and possibly Neanderthal (https://en.wikipedia.org/wiki/Neanderthal) features.[5] (https://en.wikipedia.org/wiki/Pe%C8%99tera_cu_Oase#cite_note-Trinkhaus2-5)
In June 2003 a further research team with Ștefan Milota, Ricardo Rodrigo and Mircea Gherase discovered additional human remains on the cave's surface. Thus, an entire anterior cranial skeleton was found along with a largely complete left temporal bone and a number of frontal, parietal and occipital bone segments.
Analysis of DNA from Oase-1 showed that he had approximately 6-9% Neanderthal ancestry, significantly more than any present-day human, derived (at least in part) from interbreeding 4 to 6 generations earlier. He was not more closely related to ancient European hunter-gatherers than to East Asians, suggesting that his population did not make a significant contribution to modern European ancestry. He carried modern human uniparental lineages - an extinct lineage of mitochondrial DNA haplogroup N (https://en.wikipedia.org/wiki/Haplogroup_N_(mtDNA)) and a form of Y DNA haplogroup F (https://en.wikipedia.org/wiki/Haplogroup_F-M89) exclusive of G (https://en.wikipedia.org/wiki/Haplogroup_G-M201), H (https://en.wikipedia.org/wiki/Haplogroup_H_(Y-DNA)), and IJ (https://en.wikipedia.org/wiki/Haplogroup_IJ).[6] (https://en.wikipedia.org/wiki/Pe%C8%99tera_cu_Oase#cite_note-6)



Romania
Peştera cu Oase [Oase 1]


37,000–42,000 BP
F
Y-calls Genetiker 24/6/15 pré-X (M2335)


N
Fu 2015 (http://www.ancestraljourneys.org/bibliography.shtml#Fu2015)
M2335 : 1+&1- op 7



he got extra Neanderthal admixture, later than 55-60000 years ago

his line got extinct

epoch
17-09-15, 13:21
Oase 1[edit (https://en.wikipedia.org/w/index.php?title=Pe%C8%99tera_cu_Oase&action=edit&section=2)]

Against this background, particularly noteworthy is the fact that "Oase 1" exhibits morphological traits combining a variety of archaic Homo, derived early modern human, and possibly Neanderthal (https://en.wikipedia.org/wiki/Neanderthal) features.[5] (https://en.wikipedia.org/wiki/Pe%C8%99tera_cu_Oase#cite_note-Trinkhaus2-5)
In June 2003 a further research team with Ștefan Milota, Ricardo Rodrigo and Mircea Gherase discovered additional human remains on the cave's surface. Thus, an entire anterior cranial skeleton was found along with a largely complete left temporal bone and a number of frontal, parietal and occipital bone segments.
Analysis of DNA from Oase-1 showed that he had approximately 6-9% Neanderthal ancestry, significantly more than any present-day human, derived (at least in part) from interbreeding 4 to 6 generations earlier. He was not more closely related to ancient European hunter-gatherers than to East Asians, suggesting that his population did not make a significant contribution to modern European ancestry. He carried modern human uniparental lineages - an extinct lineage of mitochondrial DNA haplogroup N (https://en.wikipedia.org/wiki/Haplogroup_N_(mtDNA)) and a form of Y DNA haplogroup F (https://en.wikipedia.org/wiki/Haplogroup_F-M89) exclusive of G (https://en.wikipedia.org/wiki/Haplogroup_G-M201), H (https://en.wikipedia.org/wiki/Haplogroup_H_(Y-DNA)), and IJ (https://en.wikipedia.org/wiki/Haplogroup_IJ).[6] (https://en.wikipedia.org/wiki/Pe%C8%99tera_cu_Oase#cite_note-6)



Romania
Peştera cu Oase [Oase 1]


37,000–42,000 BP
F
Y-calls Genetiker 24/6/15 pré-X (M2335)


N
Fu 2015 (http://www.ancestraljourneys.org/bibliography.shtml#Fu2015)
M2335 : 1+&1- op 7



he got extra Neanderthal admixture, later than 55-60000 years ago

his line got extinct

The D-stats of the Oase 1 paper are interesting not only because he was shown to be similarly unrelated to ancient HGs as to Eats Asians - so was Ust'Ishim - but other UP samples (Ust'Ishim and Kostenki 14) show that they are very unrelated to him, also Ust'Ishim.

MOESAN
17-09-15, 16:51
Unrelatd at what level?
I'm amazed by some papers abstracts: some say there is no trace of severe genic selection among moderns Humans, other seem thinking bottlenecks augment deleterious genes distribution among genome; but these people survived and passed us (partially) their DNA; aside some exceptions I'm rather pushed to believe bottlenecks augment fitness at some level, at least for local conditions. They diminish quantity of variants, but variants are not always good gifts; it's almost sure nevertheless a great variance in genes allows more adaptation in case of mesologic changes but...
the elimination of deleterious (or considered like that) Neanderthal's genes in modern genomes does not need new genes created by mutation or crossings: the crossing of populations 'sapiens sapiens' and 'neanderthal' was surely at low level and the hybrids born like that re-mated with ordinary modern Humans; the selection play was sufficient to promote again the "good" modern genes against the "bad" neanderthal genes, (very often at low speed), keeping along the "good" neanderthl ones.
All these new surveys seem being born by an initial settled idea, and not by PURE practical empirism giving way to new ideas. Maybe I'm wrong?...
I red an abstract about recessive genes being "threw off" with time: recessive genes are often a bit deleterious, but not always; and even deleterious genes are kept very long time; when genetics gets close to medecine, I use to be afraid, cautious at least; I red so much rubbish and pure contradiction.

Angela
17-09-15, 18:27
Unrelatd at what level?
I'm amazed by some papers abstracts: some say there is no trace of severe genic selection among moderns Humans, other seem thinking bottlenecks augment deleterious genes distribution among genome; but these people survived and passed us (partially) their DNA; aside some exceptions I'm rather pushed to believe bottlenecks augment fitness at some level, at least for local conditions. They diminish quantity of variants, but variants are not always good gifts; it's almost sure nevertheless a great variance in genes allows more adaptation in case of mesologic changes but...
the elimination of deleterious (or considered like that) Neanderthal's genes in modern genomes does not need new genes created by mutation or crossings: the crossing of populations 'sapiens sapiens' and 'neanderthal' was surely at low level and the hybrids born like that re-mated with ordinary modern Humans; the selection play was sufficient to promote again the "good" modern genes against the "bad" neanderthal genes, (very often at low speed), keeping along the "good" neanderthl ones.
All these new surveys seem being born by an initial settled idea, and not by PURE practical empirism giving way to new ideas. Maybe I'm wrong?...
I red an abstract about recessive genes being "threw off" with time: recessive genes are often a bit deleterious, but not always; and even deleterious genes are kept very long time; when genetics gets close to medecine, I use to be afraid, cautious at least; I red so much rubbish and pure contradiction.

I don't understand what's amazing about this abstract. It seems to represent a growing consensus as far as the general parameters are concerned, although some of their claims do contradict prior papers.

There's no question that founder effect and a bottleneck can create situations where if deleterious genes are present, they can rise to very high frequencies through the operation of drift, with unfortunate consequences for the people involved. Not all of the diseases or conditions in question result in the death of the fetus or the death of offspring in infancy. Indeed, many don't result in death until after the person has already mated, which is why the "trait" survives in the population. Some don't result in death at all, just decreased fitness of one kind or another. Just because it doesn't directly result in death doesn't mean it isn't deleterious.

Then one has to consider the operation of balancing selection as in the case of sickle cell anemia and protection against malaria. Two of subject genes mean you get sickle cell anemia and die, but one copy provides protection against malaria. So, the trait survives. I often think of King Tut when I think about this. It would seem he wasn't heterozygous for the sickle cell trait. I wonder what the frequency was among the common people?
https://simple.wikipedia.org/wiki/Balancing_selection

Of course, the traits that rise to fixation might also be advantageous. Or, you might have one set of traits that is advantageous, and one that is deleterious, both at high frequencies. However, in the case of random mutations, beneficial ones seem to be the rarest. (most seem to be neutral, thank goodness)

The examples are numerous: French Canadians, the Amish, certain communities in Sardinia, Ashkenazim, Indian communities in Britain, most of the royal families of Europe. Certain specific royal lines died out because of it. The hemophilia mutation that arose either in Queen Victoria, or immediately before her, spread throughout most of the royal houses of Europe because of the large amount of inbreeding among them. They didn't all die, but that isn't the point. I just yesterday posted a study done on a small, isolated, bottle-necked community in northeast Finland. The scientists found exceedingly high levels of schizophrenia and problems with cognitive functioning.
http://www.eupedia.com/forum/threads/31570-Enrichment-of-Genes-for-Neurodevelopmental-Disorders-in-Founder-Populations-Finland

Indeed, a lot of genetics studies that we use for populations genetics purposes were actually done because the scientists were researching the extremely high levels of certain diseases in small, isolated communities. One was done a couple of years ago on some small language isolate communities in north-east Italy for the same reason.

In terms of the Neanderthals, we have some Neanderthal genomes and some human genomes, both ancient and modern. They can be compared. They can and did test and found out that Neanderthals had 4X less diversity than any humans. They can see the approximate amount of Neanderthal ancestry in modern humans versus ancient humans. They can see that Neanderthal ancestry in humans has decreased. They can see which Neanderthal genes have survived, and they can see the areas of the genome where there was once greater Neanderthal ancestry than there is today. Those areas are enriched by new mutations. The areas have to do, per prior papers, with cognitive functioning and autoimmune disorders like diabetes, lupus etc. among others.

Drift exists. In bottle necked communities the accumulation of deleterious mutations does exist. Selection also exists. Do the scientists know everything about it? No, they don't, and they may get the details wrong, but the general parameters haven't changed for more than 100 years.

Now, in this particular case we're only dealing with an abstract(unlike in the case of Sankararaman et al 2014.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072735/

We're also dealing with simulations, apparently, not with just comparisons with the genomes. We'll see how the paper reads when it's published. I want to see the proof for this, "We present simulations showing that archaic introgression may have had a greater fitness effect than the out-of-Africa bottleneck itself.

I'm also not sure about their claim that "Our results imply that the deficit of Neanderthal DNA from functional genomic regions can be explained without the action of epistatic reproductive incompatibilities between human and Neanderthal alleles."

ED. I don't mean to say that the scientists have selection and how it operates all figured out, because they don't. There's more than a few papers about it on the ASHG List. It's enough to make my head explode just reading the abstracts! :)

Greying Wanderer
17-09-15, 23:55
bicicleur

"he got extra Neanderthal admixture, later than 55-60000 years ago. his line got extinct"

Yes, so either he was the only one or there were many like that over a long period.

It's not a big deal; I just always thought the idea there was only one mixture event and then all the neanderthals dropped dead over night seemed very silly so I'm pleased it appears to be crumbling.

Greying Wanderer
18-09-15, 00:21
moesan

"I'm rather pushed to believe bottlenecks augment fitness at some level, at least for local conditions"

Yes, with the emphasis on local conditions.

If neanderthals were adapted for the cold and AMH were pushing into colder regions (as those regions were slowly warming) then it seems to me neanderthal genes are likely to have been pretty useful to them.

With more time and warmth I can see how the neanderthal genes may have become less useful over time and then selected against - implied anyway by the modern percentages.

So it seems to me a far more likely option than single admixture is a kind of rolling wave effect as AMH moved north with neanderthal genes more favored (or less disfavored) on the forward edge of the advance and then selected out again behind the wave of advance in the warmer regions - almost like the neanderthals provided a genetic bridge into those colder regions which mostly disappeared later.

It's just a guess but I think it'll be proved eventually when some relatively recent but still heavily admixed bones are found up in the Himalayas.

Maciamo
18-09-15, 08:13
This new paper certainly proposes a thought-provoking theory. I remains skeptical though that Neanderthals, who evolved and survived for over half a million years in Europe (if we count proto-Neanderthals), would have been less well adapted to the Eurasian environment than the African Homo sapiens. Besides founder effects would have been far greater among the small group of Homo sapiens who first ventured into the Middle East then Europe and Central Asia, even if it happened in several small waves at a time, than the already well established and diversified Neanderthalian population. Actually the Homo sapiens gene pool experienced a first bottleneck in the founding population that left Africa for the Middle East, then another one among the isolated tribes that made it to Europe.

I would rather think that if Neanderthal alleles survive today among Eurasians it is chiefly because they were positively selected for their adaptive advantages. For instance Abi-Rached et al. (2011) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677943/) showed that a disproportionately high number of HLA haplotypes (regulators of the immune system) in Eurasians were inherited from Neanderthals rather than the original African Homo sapiens, because they were better adapted to local pathogens. The same is probably true of at least some fair pigmentation alleles. One reason why Neanderthalian DNA has been decreasing as a proportion of the human genome in Europe since the age of Cro-Magnon is that successive migrations from Africa to the Middle East (think hg E1b1b), and from the Middle East to Europe (Neolithic farmers, R1b to the Pontic Steppe then Europe, J2a expansion, etc.), and from southern to northern Europe (Bell Beakers, Romans) progressively lowered overall percentage of Neanderthal admixture.

bicicleur
18-09-15, 08:31
bicicleur

"he got extra Neanderthal admixture, later than 55-60000 years ago. his line got extinct"

Yes, so either he was the only one or there were many like that over a long period.

It's not a big deal; I just always thought the idea there was only one mixture event and then all the neanderthals dropped dead over night seemed very silly so I'm pleased it appears to be crumbling.




till 50 ka modern humans and Neanderthals shared similar technology
50 ka modern humans developped new technologies, which Neanderthals didn't share
while modern humans expanded, Neanderthals started to decline

bicicleur
18-09-15, 08:41
"Founder effects and bottlenecks can damage fitness by letting deleterious alleles drift to high frequencies.

I think it can work both ways.
In most bottlenecks there is a survival of the fittest and usefull genes get selected.

IMO that is how homo sapiens was born in Africa ,
that is also how the expansion of modern humans 50 ka got started, which was based on just 2 selected haplogroups, C and F

bicicleur
18-09-15, 08:47
One reason why Neanderthalian DNA has been decreasing as a proportion of the human genome in Europe since the age of Cro-Magnon is that successive migrations from Africa to the Middle East (think hg E1b1b), and from the Middle East to Europe (Neolithic farmers, R1b to the Pontic Steppe then Europe, J2a expansion, etc.), and from southern to northern Europe (Bell Beakers, Romans) progressively lowered overall percentage of Neanderthal admixture.

In that case Aurignacians should have had more Neanderthal DNA than Gravettians.
Maybe one day this will be checked.

LeBrok
18-09-15, 16:40
This new paper certainly proposes a thought-provoking theory. I remains skeptical though that Neanderthals, who evolved and survived for over half a million years in Europe (if we count proto-Neanderthals), would have been less well adapted to the Eurasian environment than the African Homo sapiens. Besides founder effects would have been far greater among the small group of Homo sapiens who first ventured into the Middle East then Europe and Central Asia, even if it happened in several small waves at a time, than the already well established and diversified Neanderthalian population. Actually the Homo sapiens gene pool experienced a first bottleneck in the founding population that left Africa for the Middle East, then another one among the isolated tribes that made it to Europe.
Exactly the dilemma I had reading their statement. I think it is just their explanation for loss of Neanderthal DNA from modern human genome. I would agree with them if our modern genome is being made "more fit" by borrowing DNA from SS African gene pool to replace Neanderthal segments. However if new "fit genome" is introduced via new mutations, then conclusion should be that neither Neanderthal nor ancient humans genome was fit as ours today.


I would rather think that if Neanderthal alleles survive today among Eurasians it is chiefly because they were positively selected for their adaptive advantages. For instance Abi-Rached et al. (2011) (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677943/) showed that a disproportionately high number of HLA haplotypes (regulators of the immune system) in Eurasians were inherited from Neanderthals rather than the original African Homo sapiens, because they were better adapted to local pathogens. I heard that staggering 95% of immune part of human genome in Asians was replaced by Neanderthal and Denisovan segments.

Angela
18-09-15, 18:43
I think it can work both ways.
In most bottlenecks there is a survival of the fittest and usefull genes get selected.

IMO that is how homo sapiens was born in Africa ,
that is also how the expansion of modern humans 50 ka got started, which was based on just 2 selected haplogroups, C and F

That's why i said this:
Of course, the traits that rise to fixation might also be advantageous. Or, you might have one set of traits that is advantageous, and one that is deleterious, both at high frequencies.

Angela
18-09-15, 20:13
LeBrok;467070]Exactly the dilemma I had reading their statement. I think it is just their explanation for loss of Neanderthal DNA from modern human genome. I would agree with them if our modern genome is being made "more fit" by borrowing DNA from SS African gene pool to replace Neanderthal segments. However if new "fit genome" is introduced via new mutations, then conclusion should be that neither Neanderthal nor ancient humans genome was fit as ours today.

I think that's a good point. I'm interested to see how the authors explain it. It depends what they mean by "new mutations". From what I recall from other papers, a lot of what they called "replacement" was in the areas of the brain associated with verbal processing, general cognitive processing, etc.

I'm not sure if all studies find "new" mutations in that area, or just removal of "older" Neanderthal genetic material. I would have to go back and check them.


I heard that staggering 95% of immune part of human genome in Asians was replaced by Neanderthal and Denisovan segments.

I wonder what the figure is for West Eurasians? The whole issue about the immune system is interesting, since the incidence of auto-immune disorders has been linked to "Neanderthal" ancestry.

I think that this paper is trying to counter assertions by some prior papers that the decrease of Neanderthal genes in humans was because the initial offspring of the matings were either sterile or so "unfit" that a lot of them didn't survive.

Just generally, then, if Neanderthal ancestry was so advantageous, why has it declined? Advantageous genes would be preserved through selection, wouldn't they?

bicicleur
18-09-15, 21:17
Just generally, then, if Neanderthal ancestry was so advantageous, why has it declined? Advantageous genes would be preserved through selection, wouldn't they?

For tens of thousands of years modern humans and Neanderthals have had the oportunity to mix.
They did on a very limited scale.
And if they did and were purified afterwards, it must in general have been very disadvantageous.
It seems the study doesn't have any material to check this, they have develloped a model.

We present simulations showing that archaic introgression may have had a greater fitness effect than the out-of-Africa bottleneck itself, saddling non-Africans with weakly deleterious alleles that accumulated as nearly neutral variants in Neanderthals.

I don't think it will prove much.

Maciamo
19-09-15, 10:33
I wonder what the figure is for West Eurasians? The whole issue about the immune system is interesting, since the incidence of auto-immune disorders has been linked to "Neanderthal" ancestry.

What HLA haplotype do you have in mind ? Based on the few Neanderthal genomes tested to date, at least HLA-A2, A11, A26, B7, B51, C*07:02, and C*16:02 came from Neanderthals. The most common among them in the European population today is HLA-A2, which is found in one quarter to a third of Europeans depending on the region. But HLA-A2 is not associated with increased autoimmunity. I also couldn't find any autoimmune link for A11, A26, C*07:02, ot C*16:02. The only clear link are for B7 and sarcoidosis, and B51 and Behçet's disease, but both are rare disease (about 1 case for every 10,000 people, and 1 case for every 100,000 people respectively). The vast majority of autoimmune diseases are caused by HLA types inherited from Homo sapiens (see list (http://www.eupedia.com/forum/threads/25151-HLA-types-and-autoimmune-diseases)).

Greying Wanderer
19-09-15, 13:08
Just generally, then, if Neanderthal ancestry was so advantageous, why has it declined? Advantageous genes would be preserved through selection, wouldn't they?

It might be that it was so diverged it was all bad *unless* there was a major compensating advantage and originally a lot of it did have a major cold environment advantage but the advantages declined as it got warmer.

If correct the most recent relatively heavily admixed populations would be up in the Himalayas somewhere.


edit: Just to be clear when I say "recent relatively heavily admixed" I still mean ancient bones not people - just a lot less ancient than currently thought.

edit2: also why Himalayas - if there was a cold advantage then the last places to have the advantage as the world warmed up would be high mountains in the far north and then if you add the moderating effect of the oceans then you're looking at high mountains in the far north as far from the oceans as possible which is Himalayas

(or if there were ever any in the Americas then the place to look for evidence would be in the middle of northern Canada somewhere like Yellowknife)

Angela
19-09-15, 13:53
What HLA haplotype do you have in mind ? Based on the few Neanderthal genomes tested to date, at least HLA-A2, A11, A26, B7, B51, C*07:02, and C*16:02 came from Neanderthals. The most common among them in the European population today is HLA-A2, which is found in one quarter to a third of Europeans depending on the region. But HLA-A2 is not associated with increased autoimmunity. I also couldn't find any autoimmune link for A11, A26, C*07:02, ot C*16:02. The only clear link are for B7 and sarcoidosis, and B51 and Behçet's disease, but both are rare disease (about 1 case for every 10,000 people, and 1 case for every 100,000 people respectively). The vast majority of autoimmune diseases are caused by HLA types inherited from Homo sapiens (see list (http://www.eupedia.com/forum/threads/25151-HLA-types-and-autoimmune-diseases)).

Sankararaman et al discussed it to some degree. It's another Reich Lab paper. It's well worth reading the whole paper.
http://www.cell.com/current-biology/fulltext/S0960-9822(15)00949-5#app3?

" we examined the 5% of genes with the highest inferred Neandertal ancestry. We do not detect tissue-specific expression patterns; however genes involved in keratin filament formation and some other biological pathways are significantly enriched in Neandertal ancestry in Europeans, East Asians, or both (Extended Data Table 1 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072735/table/T3/), SI 6). Thus, Neandertal alleles that affect skin and hair may have been used by modern humans to adapt to non-African environments."

" We also directly established the relevance of Neandertal alleles to present-day human biology by identifying alleles of Neandertal origin (SI 7), and overlapping this list with alleles that have been associated with phenotype16 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072735/#R16). We identify alleles of Neandertal origin that affect lupus, biliary cirrhosis, Crohn’s disease, optic disk size, smoking behavior, IL-18 levels and type 2 diabetes 17 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072735/#R17) (Extended Data Table 2 (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4072735/table/T4/))."

This is the paper to which they linked:
Hindorff LA, et al. Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci U S A. 2009;106:9362–9367. [PMC free article (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687147/)] [PubMed (http://www.ncbi.nlm.nih.gov/pubmed/19474294)]

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687147/

This is extended Data Table 2:
7421

7422

7425
7424
(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687147/)

Miqui Rumba
19-09-15, 14:00
Angela, Do you think that blood group RH D gene deleted in europeans and some hybrid RHDCE gene could be mutations derived from neanderthal admixture and isolation? African rh- haven't deletion in this gene, malfuction only.

Tomenable
19-09-15, 15:21
can damage fitness by letting deleterious alleles drift to high frequencies.

Only in modern welfare states, though. Under normal selective pressures deleterious alleles simply die out over time.

Unless they are deleterious for one thing but advantageous for other more important things - which is often the case.

Angela
19-09-15, 16:00
@Miqui Rumba,

I'm not aware of anything specifically on point. Did you do a google scholar search? Or Med Pub search?

@LeBrok,

There's a section of the Supplement (S1 11, page 94) that addresses your concerns.

Greying Wanderer
20-09-15, 23:13
Only in modern welfare states, though. Under normal selective pressures deleterious alleles simply die out over time.

Unless they are deleterious for one thing but advantageous for other more important things - which is often the case.


I think that's the critical point - bad genes can be selected for if they protect against something worse. So for example genes that allow survival in extreme cold don't have to be good in other environments - some might be but a lot will be either neutral or bad just by probability.

edit: hence the possibility of selection *for* certain genes on the forward edge of the AMH advance and selection *against* along the rear edge.

The analogy that works for me is the murder mystery idea of an ice dagger that melts after use.

Angela
21-09-15, 01:28
QUOTE=Tomenable;467124]Only in modern welfare states, though. Under normal selective pressures deleterious alleles simply die out over time.

Unless they are deleterious for one thing but advantageous for other more important things - which is often the case.[/QUOTE]

Really lethal genes will indeed die out over time unless there is, as I pointed out above, balancing selection, i.e. the sickle cell gene.

However, what we might call "weakly deleterious" genes, the kind that let the person survive to mate (16-20, let's say, in these early time periods) will indeed survive. Let's look at the example from Finland. Lots of people with schizophrenia survive to mate (similar genes might affect bipolar disorder and depression), so do people with pretty low intelligence, certainly people with lupus, Type 2 Diabetes, autoimmune arthritis, etc. People with inherited heart conditions or propensity to atherosclerosis can survive into their twenties or thirties. Even some of those horrendous inherited neurological disorders like Huntington's Disease often don't kick in until people are in their twenties.

MOESAN
25-09-15, 14:25
There's no question that founder effect and a bottleneck can create situations where if deleterious genes are present, they can rise to very high frequencies through the operation of drift, with unfortunate consequences for the people involved. Not all of the diseases or conditions in question result in the death of the fetus or the death of offspring in infancy. Indeed, many don't result in death until after the person has already mated, which is why the "trait" survives in the population. Some don't result in death at all, just decreased fitness of one kind or another. Just because it doesn't directly result in death doesn't mean it isn't deleterious.
[---]
Of course, the traits that rise to fixation might also be advantageous. Or, you might have one set of traits that is advantageous, and one that is deleterious, both at high frequencies. However, in the case of random mutations, beneficial ones seem to be the rarest. (most seem to be neutral, thank goodness)
[---]
The examples are numerous: French Canadians, the Amish, certain communities in Sardinia, Ashkenazim, Indian communities in Britain, most of the royal families of Europe. Certain specific royal lines died out because of it. The hemophilia mutation that arose either in Queen Victoria, or immediately before her, spread throughout most of the royal houses of Europe because of the large amount of inbreeding among them. They didn't all die, but that isn't the point. I just yesterday posted a study done on a small, isolated, bottle-necked community in northeast Finland. The scientists found exceedingly high levels of schizophrenia and problems with cognitive functioning.
Indeed, a lot of genetics studies that we use for populations genetics purposes were actually done because the scientists were researching the extremely high levels of certain diseases in small, isolated communities. One was done a couple of years ago on some small language isolate communities in north-east Italy for the same reason.
[---]
We're also dealing with simulations, apparently, not with just comparisons with the genomes. We'll see how the paper reads when it's published. I want to see the proof for this, "We present simulations showing that archaic introgression may have had a greater fitness effect than the out-of-Africa bottleneck itself.
[---]


Just to be clear about my reasoning:
we have still a lot to learn about genetics and intra genome interactions ('we' here: the scientists, not only we): fitness of genes is not only the question of separated loci in the whole genome - Just I had the impression the meaning of some abstract was that for the most bottlenecsk and/or founder effects had more bad deleterious effects than advantageous effects: I say it's hazard, and even more, the small populations are more drastically submitted to natural selection: so the remnant (surviving) populations have more chances to be well adapted to life at least at a local climatic scale - even if as you say some non immediately letal mutations (for the most: at heterozygotous level) or non-letal mutations can be passed on without elimination of the population, creating only diseases with age what is still not too fit! -
concerning royal families, OK: but here we are speaking of a very small "intermating" population with very great endogamy and helped today by a high level medecine - not comparable to Papoos or other small archaic populations -
thta said, OK with your post - just a justification of mine -

MOESAN
25-09-15, 14:27
I add: the Neanderthal question here is maybe just the proof crossings are not always all benefit, if we have kept so little of the Neand-DNA...

Tomenable
25-09-15, 16:31
survive to mate (similar genes might affect bipolar disorder and depression), so do people with pretty low intelligence.

The genetic part of intelligence is highly polygenic - there is no one single gene variant affecting intelligence, but plenty of them. There are at least 14 alleles related somehow to cognitive predispositions. At least one of them is deleterious, most of them are beneficial - of the 10 alleles which are believed to be for sure beneficial, 9 are found only in humans, and just 1 is found in other primates too. Moreover, it is very probable that each of the 14 alleles is responsible for different aspects of intelligence and predispositions to different types of mental activity. For example it has been proven that Australian Aborigines have high visual-spatial intelligence, despite having low overall IQ test scores. Aborigines are famous for their quality art:

http://www.aboriginalartonline.com/index.php

As I wrote, 9 of 10 alleles which correlate positively with educational attainment and IQ scores are human-specific, only 1 is present in chimps:


Nine of the 10 alleles associated with educational attainment were derived, thus unique to humans and not shared with non-human primates. This result was significant (p=0.01) and is predicted on the basis of the assumption that humans have evolved by natural selection to become more intelligent than their primate cousins. The results show that this evolutionary process, which was already far advanced at the time when modern humans spread across the globe approximately 65,000 years before present, has continued in modern human populations after that time. It invalidates theories that assume, explicitly or implicitly, that human cognitive evolution has ended with the first appearance of physically modern Homo sapiens (e.g., Tooby and Cosmides, 1992).

Also one of them - rs13188378(G) - appears to be almost completely absent from Sub-Saharans, so I wonder if it is of Neanderthal origin:

http://therightstuff.biz/content/images/2015/09/04-Piffer_2013_04.jpg

More on these 14 identified mutations can be found for example in papers by D. Piffer 2013 & 2014, E. Kirkegaard 2014, C. Rietveld 2013:

Piffer 2013 - http://emilkirkegaard.dk/en/wp-content/upl...ment-and-IQ.pdf (http://emilkirkegaard.dk/en/wp-content/uploads/Factor-Analysis-of-Population-Allele-Frequencies-as-a-Simple-Novel-Method-of-Detecting-Signals-of-Recent-Polygenic-Selection-The-Example-of-Educational-Attainment-and-IQ.pdf)
Piffer 2014 - http://www.ibc7.org/article/journal_v.php?sid=317
Kirkegaard 2014 - http://openpsych.net/OBG/2014/04/the-genet...nitive-ability/ (http://openpsych.net/OBG/2014/04/the-genetic-correlation-between-educational-attainment-intracranial-volume-and-iq-is-due-to-recent-polygenic-selection-on-general-cognitive-ability/)
Rietveld 2013 (https://www.sciencemag.org/content/340/6139/1467.abstract) - http://scholar.harvard.edu/files/laibson/f...ence_053013.pdf (http://scholar.harvard.edu/files/laibson/files/gwas_science_053013.pdf)
Benyamin 2013 - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935975/
Gosso 2007 - http://www.biomedcentral.com/1471-2350/8/66

However, whatever IQ tests measure, it is not all just genetically determined. Environmental and cultural factors also play their roles.

Here is a good video with James Flynn talking about the Flynn Effect and why we score better in IQ tests than our grandparents:

https://www.youtube.com/watch?v=9vpqilhW9uI


https://www.youtube.com/watch?v=9vpqilhW9uI

Tomenable
26-09-15, 13:42
The Igbo ethnic group of Nigeria have probably the highest IQ in Sub-Saharan Africa:

http://www.unz.com/article/the-iq-gap-is-no-longer-a-black-and-white-issue/

https://en.wikipedia.org/wiki/Igbo_people (http://www.unz.com/article/the-iq-gap-is-no-longer-a-black-and-white-issue/)