PDA

View Full Version : More on the Genetic Cost of Neanderthal Introgression



Angela
02-11-15, 17:57
The Genetic Cost of Neanderthal Introgression Kelley Harris, Rasmus Nielsen
Abstract"Approximately 2-4% of the human genome is in non-Africans comprised of DNA intro- gressed from Neanderthals. Recent studies have shown that there is a paucity of introgressed DNA around functional regions, presumably caused by selection after introgression. This observation has been suggested to be a possible consequence of the accumulation of a large amount of Dobzhansky-Muller incompatibilities, i.e. epistatic effects between human and Neanderthal specific mutations, since the divergence of humans and Neanderthals approx. 400-600 kya. However, using previously published estimates of inbreeding in Neanderthals, and of the distribution of fitness effects from human protein coding genes, we show that the average Neanderthal would have had at least 40% lower fitness than the average human due to higher levels of inbreeding and an increased mutational load, regardless of the dominance coefficients of new mutations. Using simulations, we show that under the assumption of additive dominance effects, early Neanderthal/human hybrids would have experienced strong negative selection, though not so strong that it would prevent Neanderthal DNA from entering the human population. In fact, the increased mutational load in Neanderthals predicts the observed reduction in Neanderthal introgressed segments around protein coding genes, without any need to invoke epistasis. The simulations also predict that there is a residual Neanderthal derived mutational load in non-African humans, leading to an average fitness reduction of at least 0.5%. Although there has been much previous debate about the effects of the out-of-Africa bottleneck on mutational loads in non-Africans, the significant deleterious effects of Neanderthal introgression have hitherto been left out of this discussion, but might be just as important for understanding fitness differences among human populations. We also show that if deleterious mutations are recessive, the Neanderthal admixture fraction would gradually increase over time due to selection for Neanderthal haplotypes that mask human deleterious mutations in the heterozygous state. This effect of dominance heterosis might partially explain why adaptive introgression appears to be widespread in nature."



http://biorxiv.org/content/early/2015/10/31/030387

The paper is open access.

The Strength of Selection Against Neanderthal Introgression Ivan Juric, Simon Aeschbacher, Graham Coop
Abstract
"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 there are systematically lower levels of initial introgression on the X chromosome, a finding consistent with a strong sex bias in the initial matings between the populations. 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"

Tomenable
02-11-15, 23:13
But what about heterosis?:

https://en.wikipedia.org/wiki/Heterosis


Heterosis, hybrid vigor, or outbreeding enhancement, is the improved or increased function of any biological quality in a hybrid offspring. The adjective derived from heterosis is heterotic. An offspring exhibits heterosis if its traits are enhanced as a result of mixing the genetic contributions of its parents.

Multi-culti myth, it seems?

Angela
02-11-15, 23:19
The Harris-Nielsen paper discusses it. The surprise for me is how "unfit" they were...massive amounts of inbreeding, apparently, apart from anything else.

From the abstract to their paper:
"We also show that if deleterious mutations are recessive, the Neanderthal admixture fraction would gradually increase over time due to selection for Neanderthal haplotypes that mask human deleterious mutations in the heterozygous state. This effect of dominance heterosis might partially explain why adaptive introgression appears to be widespread in nature."

oriental
03-11-15, 00:08
They were grouping in small numbers and the cold environment kept them in caves. So it was inbreeding that probably did them in as di the pharaohs of Egypt who kept their godly blood and married their sisters. Even the Ptolemies followed that route as the Cleopatras seem to be inbred except for the last one who was involved with Julius Caesar(Liz Taylor, no less) and Marc Antony (Richard Burton or Jenkins).

LeBrok
04-11-15, 03:36
Perhaps we should notice that almost all of modern humans have Neanderthal DNA, and this is supposedly from only few mating encounters. It means that in Neanderthal DNA there was something very important for human health and survival that it was embraced and spread like wildfire through all out of Africa HS. This despite of big part of DNA which is judged by some scientists as genetically more "expensive" or unfit.
Other thing is that first we should get human DNA from pre-mixing with Neanderthal to definitively know what was HS and what came from Nd.

bicicleur
04-11-15, 11:48
who got Neanderthal admixture ?

it looks like haplo C & F got it, 55-60.000 years ago, just before their expansion which finaly caused the extinction of Neanderthals

haplo E didn't have it,we know from 4500 year old the E1b1 male in a cave in Ethiopia on 2000 meter altitude

did haplo D have it ? DE split some 66.000 years ago and D expanded some 49.000 years ago, probably near the Gulf of Bengal, but where was D 55-60.000 years ago?

there were later admixture events, like this one in Romania, who had 6 % admixture as recent as 4 to 6 generations ago, he was probably pré-NO, but it looks like his branch got extinct



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)



so, were ther more post 55-60 ka admixture advents, and if so, were those admixed tribes capable of survival?
and if not, what was special about the 55-60 ka admixture event?

Angela
04-11-15, 17:40
Perhaps we should notice that almost all of modern humans have Neanderthal DNA, and this is supposedly from only few mating encounters. It means that in Neanderthal DNA there was something very important for human health and survival that it was embraced and spread like wildfire through all out of Africa HS. This despite of big part of DNA which is judged by some scientists as genetically more "expensive" or unfit.
Other thing is that first we should get human DNA from pre-mixing with Neanderthal to definitively know what was HS and what came from Nd.

I think there's definitely need for further research. They don't have it all nailed down yet.

There is this in the paper as for the amount of admixture:
"If most mutations have additive dominance effects and multiplicative effects across loci, initial admixture would have to have been as high as 10% to explain the amount of admixture observed today. In contrast, if most mutations are recessive, an initial admixture fraction closer to 1% appears most plausible. We did not model selection for new beneficial mutations here, and it is possible that such selection might also have helped facilitate introgression, particularly in the first generations where selection against hybrids would otherwise have been strong."



"The distribution of dominance effects in humans is not well characterized. But it is likely that introgressed Neanderthal DNA has been subject to a selective tug-of-war, with selection in DNA in regions where humans carry recessive deleterious mutations and selection disfavoring Neanderthal alleles that have additive or dominant effects."

Also, " Introgression of recessive mutations is predicted to affect fitness in a more complex way. Some adaptive benefits will result from Neanderthal and human haplotypes masking one another’s deleterious alleles, but Hill-Robertson interference may also hurt fitness as overdominant selection at recessive sites drags linked dominant Neanderthal alleles to higher frequency. In addition, Neanderthal haplotypes are predicted to have worse recessive burdens than human ones if they become homozygous due to selection or inbreeding."


At any rate, the authors believe that the Neanderthals, as perhaps earlier hominids were doomed to extinction because of their lack of fitness, and the only reason their dna survives is because it became mixed with that of anatomically modern humans.

" It is an open question whether archaic hominins’ deleterious mutation load contributed to their decline and extinction. However, there is clear evidence that Neanderthals escaped total genetic extinction by interbreeding with the anatomically modern humans who left Africa between 50 and 100 thousand years ago [1]"

Tomenable
04-11-15, 18:50
At any rate, the authors believe that the Neanderthals, as perhaps earlier hominids were doomed to extinction because of their lack of fitness, and the only reason their dna survives is because it became mixed with that of anatomically modern humans.


"It is an open question whether archaic hominins’ deleterious mutation load contributed to their decline and extinction. However, there is clear evidence that Neanderthals escaped total genetic extinction by interbreeding with the anatomically modern humans who left Africa between 50 and 100 thousand years ago [1]"
So they are telling us that Neanderthals - who lived in Eurasia for at least 150,000 years - were just about to get extinct exactly when anatomically modern humans met them? They survived for at least 160,000 years - why are we assuming that they would not have been able to survive for the next 40,000 years (i.e. until 2015 AD)? By now, modern humans have lived outside of Africa for a much shorter time than Neanderthals did.

Sorry, I don't buy this story. I don't think that Neanderthals were doomed to be finished off by nature itself, without our "help". When spoken by the ones who caused their extinction, it sounds a bit like claiming that Jews would have jumped into gas chambers even without Nazi "help".

Really, this sounds hilarious - so humans did not cause their extinction, but actually "saved them", or at least some of their genetic material... ? :confused2: :laughing:

bicicleur
04-11-15, 20:20
So they are telling us that Neanderthals - who lived in Eurasia for at least 150,000 years - were just about to get extinct exactly when anatomically modern humans met them? They survived for at least 160,000 years - why are we assuming that they would not have been able to survive for the next 40,000 years (i.e. until 2015 AD)? By now, modern humans have lived outside of Africa for a much shorter time than Neanderthals did.

Sorry, I don't buy this story. I don't think that Neanderthals were doomed to be finished off by nature itself, without our "help". When spoken by the ones who caused their extinction, it sounds a bit like claiming that Jews would have jumped into gas chambers even without Nazi "help".

Really, this sounds hilarious - so humans did not cause their extinction, but actually "saved them", or at least some of their genetic material... ? :confused2: :laughing:

I would even say more.
Homo sapiens was in the Persian Gulf area since 125 ka (Jebel Faya) and expanded further east (teeth discovered in China > 80 ka).
Neanderthals prevented homo sapiens till 50 ka to enter Europe, that is 75000 years.
50 ka homo sapiens invented stone blade tools instead of 300 ka Neanderthal Levalois flake tools. That was their breakthrough.

haplo BT is 125000 years old
between 125 ka and 50 ka the only ofshoot which survived were just 5 branches B ,C, D, E and F, of which D fled east and B and E fled back to Africa
I'd say Neanderthals were about to exterminate homo sapiens as they did with Denisovans

Angela
04-11-15, 23:36
So they are telling us that Neanderthals - who lived in Eurasia for at least 150,000 years - were just about to get extinct exactly when anatomically modern humans met them? They survived for at least 160,000 years - why are we assuming that they would not have been able to survive for the next 40,000 years (i.e. until 2015 AD)? By now, modern humans have lived outside of Africa for a much shorter time than Neanderthals did.

Sorry, I don't buy this story. I don't think that Neanderthals were doomed to be finished off by nature itself, without our "help". When spoken by the ones who caused their extinction, it sounds a bit like claiming that Jews would have jumped into gas chambers even without Nazi "help".

Really, this sounds hilarious - so humans did not cause their extinction, but actually "saved them", or at least some of their genetic material... ? :confused2: :laughing:

Sorry, where did you see that the authors proposed that the Neanderthals were on the verge of extinction. I thought what they were saying was that the Neanderthals were so "genetically unfit" that they could have gone extinct eventually, as did other more archaic hominins.

The estimates and probabilities are based on the calculation of an "effective population size" of 1000 for Neanderthals. They're also based on the actual deleterious genes found in the Neanderthal genome.

This is the fourth or fifth paper, from labs all around the world, to come to a similar conclusion. You think it's some sort of conspiracy? To what end?

If you think their models are incorrect, or you think the Neanderthal genes were not as deleterious as the authors claimed, I'd be interested to hear the particulars where you think they went wrong.

Angela
04-11-15, 23:53
Sorry, where did you see that the authors proposed that the Neanderthals were on the verge of extinction. I thought what they were saying was that the Neanderthals were so "genetically unfit" that they could have gone extinct eventually, as did other more archaic hominins.

The estimates and probabilities are based on the calculation of an "effective population size" of 1000 for Neanderthals. They're also based on the actual deleterious genes found in the Neanderthal genome.

This is the fourth or fifth paper, from labs all around the world, to come to a similar conclusion. You think it's some sort of conspiracy? To what end?

If you think their models are incorrect, or you think the Neanderthal genes were not as deleterious as the authors claimed, I'd be interested to hear the particulars where you think they went wrong.


A discussion of the two papers can be found on this blog:
https://evolution-institute.org/blog/how-admixture-with-neanderthals-may-have-affected-human-populations/


One of the papers is more cautious about any claims of possible Neanderthal extinction based on their "unfitness", but agrees on the other points.

"However, Juric et al. caution that a direct cause and effect relationship will be difficult to identify, in no small part because of genetic adaptations, soft selection and epistatic effects, but also because of Neanderthal cultural adaptations (which will not appear in the genome) that might have offset such disadvantages."

Greying Wanderer
05-11-15, 04:36
Thing is, Neanderthals survived a huge amount of time in a very harsh climate so it's hard to believe they were that fragile. I'd suggest the problem was more likely the opposite.

https://en.wikipedia.org/wiki/Neanderthal#Climate_change


Studies on Neanderthal body structures have shown that they needed more energy to survive than any other species of hominid. Their energy needs were up to 100 to 350 kcal (420 to 1,460 kJ) more per day comparing to projected anatomically modern human males weighing 68.5 kg (151 lb) and females 59.2 kg (131 lb)

Maybe Megahominids needed Megafauna to eat and when the Megafauna went they had to shrink back down to human size...I mean disappear :)

https://en.wikipedia.org/wiki/Pleistocene_megafauna

epoch
05-11-15, 11:55
A discussion of the two papers can be found on this blog:
https://evolution-institute.org/blog/how-admixture-with-neanderthals-may-have-affected-human-populations/


One of the papers is more cautious about any claims of possible Neanderthal extinction based on their "unfitness", but agrees on the other points.

"However, Juric et al. caution that a direct cause and effect relationship will be difficult to identify, in no small part because of genetic adaptations, soft selection and epistatic effects, but also because of Neanderthal cultural adaptations (which will not appear in the genome) that might have offset such disadvantages."

I have a private little theory (i.e. wild speculation) on this. We know that at the beginning of the Aurignacian (Pre-Aurignacian and Proto-Aurignacian) a lot of AMH-ish human remains are found that have Neanderthal traits. Oase 1 had them and indeed he was proven to be far more interbred with Neanderthals than modern humans, or Ust'Ishim and K14. But there are mandibles with AMH traits (Mezzena jaw) found in Northern Italy from about the same time that have Neanderthal mtdna.

We also know that Neanderthal DNA avoids the X chromosome, which is considered evidence for reduced fertility in hybrids.

What if the Oase 1 people and Neanderthals did interbreed extensively and it was the interbreeding that actually reduced Neanderthal fertility, as well as the reduction of fertility of the AMH population that they interbred with? Oase 1 is clearly unancestral to Europeans. I suspect the downfall of the Neanderthals may also be the downfall of the AMH's that were closely related to them. Also, we constantly discuss Neanderthal admixture in humans but the other way around, AMH admixture in Neanderthals may be just as interesting.

I have some links at home, maybe I'll find the time to look them up.


EDIT: Links that may be interesting

http://bioculturalevolution.net/2015/06/12/the-protoaurignacian-didnt-trigger-anything/
http://bioculturalevolution.net/2015/06/27/read-all-about-it-oase-i-neandertal-admixture-article-published/

epoch
05-11-15, 12:56
Perhaps we should notice that almost all of modern humans have Neanderthal DNA, and this is supposedly from only few mating encounters. It means that in Neanderthal DNA there was something very important for human health and survival that it was embraced and spread like wildfire through all out of Africa HS. This despite of big part of DNA which is judged by some scientists as genetically more "expensive" or unfit.
Other thing is that first we should get human DNA from pre-mixing with Neanderthal to definitively know what was HS and what came from Nd.

While only very few mating encounters are visible in present day humans and K14 and Ust'Ishim, Oase 1 shows a completely different picture:


When we remove the seven longest segments, the estimate of Neanderthal ancestry in Oase 1 drops from 7.3% to 4.8%, which is still around twice the 2.0–2.9% estimated for the French, Han, Kostenki and Ust’-Ishim individuals in this remaining part of the genome. This additional Neanderthal ancestry could reflect an older Neanderthal admixture into the ancestors of Oase 1, or that we failed to find all segments of recent Neanderthal ancestry.

http://bioculturalevolution.net/2015/06/27/read-all-about-it-oase-i-neandertal-admixture-article-published/
(http://bioculturalevolution.net/2015/06/27/read-all-about-it-oase-i-neandertal-admixture-article-published/)
Oase 1 has been given far too little attention. It is almost contemporary to K14 but shows hardly any affinity with WHGs. K14 OTOH seems very ancestral to Loschbour and clearly related to MA1.

http://www.nature.com/nature/journal/v524/n7564/fig_tab/nature14558_ST1.html

Angela
09-11-15, 20:51
This paragraph is on point for our discussion about the relationship between effective population size and genetic load. It's from Razib Khan's latest blog post.

"The basic issue is that in small populations genetic drift has the potential to overwhelm the power of selection in purging deleterious alleles. How deleterious an allele is varies. Some alleles have very strong negative selection coefficients. For example, those with dominant lethal effects are going to be purged immediately for obvious reasons (if it’s dominant, it’s always expressed, and if it’s lethal, it isn’t passed on). The situation differs for those with recessive expression patterns. Even if it is lethal in homozygous form, an allele can persist at low frequency if the population is random mating, as the vast majority of copies will be in heterozygotes whose fitness is not impinged. But if the selection coefficient is low enough than even dominantly expressed alleles may not be purged. The variance in allele frequencies due to sampling is inversely proportional to the population size, so as that converges upon the selection coefficient in terms of magnitude, the efficacy of natural selection diminishes. This is at the heart of the nearly neutral theory (https://en.wikipedia.org/wiki/Nearly_neutral_theory_of_molecular_evolution), which suggests that a lot of variation is due to the input of very weakly deleterious alleles which can’t be purged in population sizes where drift is above a particular threshold."

This is the paper to which he is referring:
http://onlinelibrary.wiley.com/doi/10.1111/evo.12802/abstract

This is the blog entry:
http://www.unz.com/gnxp/size-population-matters-for-inbreeding/

Greying Wanderer
24-11-15, 06:10
I think they're ignoring relative selection pressure.

A small population stuck on a small but otherwise okay island has a small population and average selection pressure.

Neanderthals had a small population and extreme selection pressure so seems to me the model might have been like more lions i.e. small populations of predator mammals where one flaw = dead.

I don't see how a population could survive the harsh conditions otherwise.

So more likely too specialized imo - big cold adapted mega hominids for mega fauna - and when the mega fauna died out either the mega hominids died out too (or shrunk into the human population).