The lingering load of archaic admixture in modern human populations

[bicicleur 2]

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]

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).

 

[Greying Wanderer]

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]

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).

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, 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. 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 (Extended Data Table 2)."

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] [PubMed]

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

This is extended Data Table 2:

 

[Miqui Rumba]

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]

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]

@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]

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]

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]

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]

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]

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:

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
Piffer 2014 - http://www.ibc7.org/article/journal_v.php?sid=317
Kirkegaard 2014 - http://openpsych.net/OBG/2014/04/the-genet...nitive-ability/
Rietveld 2013 - http://scholar.harvard.edu/files/laibson/f...ence_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

 

[Tomenable]

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/

[url]https://en.wikipedia.org/wiki/Igbo_people
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