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Angela
11-11-16, 22:42
See:
http://www.livescience.com/56800-why-humans-dont-have-more-neanderthal-genes.html

This is the actual paper:

The Strength of Selection against Neanderthal Introgressionhttp://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340

"Hybridization between humans and Neanderthals has resulted in a low level of Neanderthal ancestry scattered across the genomes of many modern-day humans. After hybridization, on average, selection appears to have removed Neanderthal alleles from the human population. Quantifying the strength and causes of this selection against Neanderthal ancestry is key to understanding our relationship to Neanderthals and, more broadly, how populations remain distinct after secondary contact. Here, we develop a novel method for estimating the genome-wide average strength of selection and the density of selected sites using estimates of Neanderthal allele frequency along the genomes of modern-day humans. We confirm that East Asians had somewhat higher initial levels of Neanderthal ancestry than Europeans even after accounting for selection. We find that the bulk of purifying selection against Neanderthal ancestry is best understood as acting on many weakly deleterious alleles. We propose that the majority of these alleles were effectively neutral—and segregating at high frequency—in Neanderthals, but became selected against after entering human populations of much larger effective size. While individually of small effect, these alleles potentially imposed a heavy genetic load on the early-generation human–Neanderthal hybrids. This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought."

LeBrok
12-11-16, 02:16
See:
http://www.livescience.com/56800-why-humans-dont-have-more-neanderthal-genes.html

This is the actual paper:

The Strength of Selection against Neanderthal Introgression

http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340

"Hybridization between humans and Neanderthals has resulted in a low level of Neanderthal ancestry scattered across the genomes of many modern-day humans. After hybridization, on average, selection appears to have removed Neanderthal alleles from the human population. Quantifying the strength and causes of this selection against Neanderthal ancestry is key to understanding our relationship to Neanderthals and, more broadly, how populations remain distinct after secondary contact. Here, we develop a novel method for estimating the genome-wide average strength of selection and the density of selected sites using estimates of Neanderthal allele frequency along the genomes of modern-day humans. We confirm that East Asians had somewhat higher initial levels of Neanderthal ancestry than Europeans even after accounting for selection. We find that the bulk of purifying selection against Neanderthal ancestry is best understood as acting on many weakly deleterious alleles. We propose that the majority of these alleles were effectively neutral—and segregating at high frequency—in Neanderthals, but became selected against after entering human populations of much larger effective size. While individually of small effect, these alleles potentially imposed a heavy genetic load on the early-generation human–Neanderthal hybrids. This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought."
Ha, this is what I figured out in a thread about neanderthal proportion in ancient genomes (can't remember exact name of the thread).

PS. Your new 'face" freaks me out Angela. ;)

Maciamo
12-11-16, 08:39
A similar process might explain why the apparently African admixture in ancient Scandinavian/Germanic people (http://www.eupedia.com/forum/threads/33084-African-admixture-in-ancient-Germanic-Scandinavian-people) disappeared over time. In fact, that "African" admixture might well be Neanderthal rather than African. That would make more sense.

Sile
12-11-16, 19:57
most west-asian, south-asian and east-asian have greater denisovan % than Neanderthal %

mine is 3.1% denisovan and 1.5% neatherthal


my guess is that south-west asian and any African should have more Neanderthal though

LeBrok
12-11-16, 22:53
Ha, this is what I figured out in a thread about neanderthal proportion in ancient genomes (can't remember exact name of the thread).

Found it. This is what I predicted:

Looking at the big picture, we can't escape a conclusion, that most of Neanderthal DNA was of no consequence to people, to human genome. Containing alleles, which were not better or worse than HSS's ones. A little different in form and expression but likewise useful and likewise working well.
2-3% amount of their DNA, in every one of us, points to the ratio of Neanderthals to Humans during mixing, and final level left in Paleolithic humans after last mixing event. And it is pretty much steady since.

http://www.eupedia.com/forum/threads/32450-Ancient-dna-and-human-evolution?p=484073&viewfull=1#post484073

Looks like I understand natural selection well. Nice to be vindicated. :)

Angela
12-11-16, 23:38
You may be right, but that isn't what the scientists found, is it? This is what they said:

"We find that the bulk of purifying selection against Neanderthal ancestry is best understood as acting on many weakly deleterious alleles. We propose that the majority of these alleles were effectively neutral—and segregating at high frequency—IN NEANDERTHALS, but became selected against after entering human populations of much larger effective size. While individually of small effect, these alleles potentially imposed a heavy genetic load on the early-generation human–Neanderthal hybrids. "

bicicleur
14-11-16, 12:15
The researchers suggested that many mildly negative gene variants, or alleles, were able to persist in Neanderthals because Neanderthals had much smaller populations than modern humans. However, when these gene variants made their way into modern humans, modern humans' larger populations — and thus bigger gene pools — were better at winnowing out these deleterious alleles.

this is different from We propose that the majority of these alleles were effectively neutral—and segregating at high frequency—IN NEANDERTHALS

if I understand correct the genes were midly harmfull in both populations but natural selection would only work in populations that are dense enough
I doubt though that modern human populations were denser than Neanderthals prior to 50 ka
after 50-45 ka populations started to grow denser in some areas
by that time modern humans had developped technologies to outcompete the Neanderthals

Angela
14-11-16, 14:15
Bicicleur, my post number 6 is a quote from their abstract.

bicicleur
14-11-16, 15:15
Bicicleur, my post number 6 is a quote from their abstract.

yes, do you know what they mean by 'effectively neutral-and segregating at high frequency-' ?

Angela
14-11-16, 16:28
OK, now I get your point, I think. Were these alleles mildly deleterious in both populations, but the larger effective population size in AMHs allowed for natural selection to operate against them, or were they effectively neutral in Neanderthals but not in AMHs? Or were the specific alleles they are examining effectively neutral in both, but there has been weak selection against them in AMHs because of larger population size? Is that it?

Unfortunately, I don't know the answer. I don't think the authors made it at all clear.

This is all that I could find, and it doesn't answer the question, really.

"Levels of genetic diversity within Neanderthals are consistent with a very low long-term effective population size compared to AMH, i.e. a higher rate of genetic drift [5 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref005)]. This suggests that weakly deleterious exonic alleles may have been effectively neutral and drifted up in frequency in Neanderthals [28 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref028)–30 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref030)], only to be slowly selected against after introgressing into modern human populations of larger effective size. "

I don't see how they get from a higher rate of genetic drift in Neanderthals and less genetic diversity "suggests that weakly deleterious exonic alleles may have been effectively neutral.

"Therefore, a model in which the bulk of Neanderthal alleles, which are now deleterious in modern humans, simply drifted up in frequency due to the smaller effective population size of Neanderthals seems quite plausible. This conclusion has also been independently reached by a recent study via a simulation-based approach [32 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref032)]."

I found the discussion of the X chromosome interesting too.

" For the EUR samples, however, the confidence intervals for μXsX do not include zero, which suggests significant evidence for selection against introgression on the X, potentially stronger than that on the autosomes. Note that the selection coefficients on the X (sX, Table 1 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen-1006340-t001)) are still on the order of one over the effective population size of modern humans, as was the case for the autosomes. Therefore, differences in effective population size between Neanderthals and modern humans, and hence in the efficacy of selection, might well explain observed patterns of introgression on the X as well as on the autosomes. If the exonic density of selection against Neanderthal introgression was indeed stronger on the X, one plausible explanation is the fact that weakly deleterious alleles that are partially recessive would be hidden from selection on the autosomes but revealed on the X in males [33 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref033)–35 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref035)].Our results are potentially consistent with the notion that the present-day admixture proportion on the X chromosome was influenced not only by stronger purifying selection, but also by a lower initial admixture proportion p0,X (Fig 4 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen-1006340-g004)). Lower p0,X is consistent with a bias towards matings between Neanderthal males and human females, as compared to the opposite. Based on our point estimates, and if we attribute the difference between the initial admixture frequency between the X and the autosomes (p0,X and p0,A) exclusively to sex-biased hybridization, our result would imply that matings between Neanderthal males and human females were about three times more common than the opposite pairing (S2 Text (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.s002)). However, as mentioned above, there is a high level of uncertainty about our X chromosome point estimates. Therefore, we view this finding as very provisional."

Likewise, they make the point that :

"This is not to say that alleles of larger effect, in particular those underlying ecological or behavioral differences, did not exist, but rather that they are not needed to explain the observed relationship between gene density and Neanderthal ancestry. Alleles of large negative effect would have quickly been removed from admixed populations, and would likely have led to extended genomic regions showing a deficit of Neanderthal ancestry as described by [9 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref009), 13 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref013), 47 (http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1006340#pgen.1006340.ref047)]"

LeBrok
15-11-16, 03:30
Lower p0,X is consistent with a bias towards matings between Neanderthal males and human females, as compared to the opposite.

Oh, the horny bugger. ;)

bicicleur
15-11-16, 18:34
@Angela,

I don't understand how certain genes could be mildly harmfull for modern humans but not for Neanderthals, but maybe a special mechanism of combination with other genes is at work (like you told me about sickle cell and malaria).
I don't think the authors give an explanation to that either.
That is why I think the absence of selection in less dense populations could be an alternative explanation/theory.

LeBrok
15-11-16, 20:42
@Angela,

I don't understand how certain genes could be mildly harmfull for modern humans but not for Neanderthals, but maybe a special mechanism of combination with other genes is at work (like you told me about sickle cell and malaria).Yes, there is always an interaction between genes, they almost never work alone.

I don't think the authors give an explanation to that either.
That is why I think the absence of selection in less dense populations could be an alternative explanation/theory.Neanderthals lived in Ice Age Europe for 700,000 years. This is long enough to get genetically in tune with environment. I don't think they were carrying many "bad" genes. Everything bad should have been weeded out already. On other hand they might not have had the best mutations yet and best adaptations, due to their low population numbers, therefore slow evolution.

bicicleur
15-11-16, 21:10
the Neanderthals emerged in Europe 300 ka, but they split from Denisovan some 450 ka
the Neanderthals were probably the version adapted to Europe from their 450 ka ancestors (found in Sima de Los Huesos)
however admixture is supposed to have happened in SW Asia 55-60 ka
Neanderthals were in SW Asia only +/- 90 ka*, so they were not more adapt to SW Asia than modern humans, who were in SW Asia allready 125 ka

*there were also Neanderthals in the Levant ca 200 - 120 ka but that branch was replaced by the Skhull/Qafzeh modern humans, and probaly got extinct,
the 90 ka Neanderthals in SW Asia were a new arrival from Europe who replaced the Skhull/Qafzeh modern humans

untill ca 50 ka modern humans were not able to outcompete Neanderthals
I guess modern human populations were not denser than Neanderthals populations either uptill then

Angela
15-11-16, 21:46
@Angela,

I don't understand how certain genes could be mildly harmfull for modern humans but not for Neanderthals, but maybe a special mechanism of combination with other genes is at work (like you told me about sickle cell and malaria).
I don't think the authors give an explanation to that either.
That is why I think the absence of selection in less dense populations could be an alternative explanation/theory.

I basically agree with that.

I also wish they'd given some examples of these "small effect" genes. Just how small is small? :) What functions did they impact? Prior papers have postulated things like schizophrenia, and speech disorders, and auto-immune disorders are tied to Neanderthal introgression. Those things won't kill you, so are they small effect genes?

Also, everything I know suggests that every important trait is indeed the result of a large number of small effect genes working together. So, one gene alone might not seem to be affecting functioning very much, but the aggregate effect of a lot of "small effect" genes might be a very different matter.

I just don't think they know enough about this, or else some of the answers are in this paper but I'm just not understanding them.

Anyway, even accounting for the differences in mating proportions, there seems to have been more purging on the "X", which is where the coding for a lot of very important functions takes place.