The Selection Landscape and Genetic Legacy of Ancient Eurasians. Preprint.

[real expert]

Abstract

The Eurasian Holocene (beginning c. 12 thousand years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical and mental health of present-day populations. Using an imputed dataset of >1600 complete ancient genome sequences, and new computational methods for locating selection in time and space, we reconstructed the selection landscape of the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify major selection signals related to metabolism, possibly associated with the dietary shift occurring in this period. We show that the selection on loci such as the FADS cluster, associated with fatty acid metabolism, and the lactase persistence locus, began earlier than previously thought. A substantial amount of selection is also found in the HLA region and other loci associated with immunity, possibly due to the increased exposure to pathogens during the Neolithic, which may explain the current high prevalence of auto-immune disease, such as psoriasis, due to genetic trade-offs. By using ancient populations to infer local ancestry tracks in hundreds of thousands of samples from the UK Biobank, we find strong genetic differentiation among ancient Europeans in loci associated with anthropometric traits and susceptibility to several diseases that contribute to present-day disease burden. These were previously thought to be caused by local selection, but in fact can be attributed to differential genetic contributions from various source populations that are ancestral to present-day Europeans. Thus, alleles associated with increased height seem to have increased in frequency following the Yamnaya migration into northwestern Europe around 5,000 years ago. Alleles associated with increased risk of some mood-related phenotypes are overrepresented in the farmer ancestry component entering Europe from Anatolia around 11,000 years ago, while western hunter-gatherers show a strikingly high contribution of alleles conferring risk of traits related to diabetes. Our results paint a picture of the combined contributions of migration and selection in shaping the phenotypic landscape of present-day Europeans that suggests a combination of ancient selection and migration, rather than recent local selection, is the primary driver of present-day phenotypic differences in Europe.

https://www.biorxiv.org/content/10.1101/2022.09.22.509027v1.article-info

 

[Angela]

Sorry, out of juice.

Interesting paper. I'll read it later.

Do they differentiate in the paper between diseases like bi-polar disorder and depression? I ask, because papers on modern populations find a difference in frequency south to north, with bi-polar disorder on a south/north cline, and depression on a north/south cline.

 

[Bergin]

Sorry, out of juice.

Interesting paper. I'll read it later.

Do they differentiate in the paper between diseases like bi-polar disorder and depression? I ask, because papers on modern populations find a difference in frequency south to north, with bi-polar disorder on a south/north cline, and depression on a north/south cline.

There is some data on figure4 / graph C (maybe some also in graph B, but you need eagle genes to read it).
No North-South, but Component based (EHG, WHG ,...)
What i find funny is the Farmer (&Yamnaya) blond hair traits. Also that physical stature is not selected but ancestral.

Farmers have some bad mood traits, but better behave for Alzhaimer and diabetes. Also have a lower Basal metabolic rate, which IMO only might mean longer lifespan.

In the other pictures they also analyze some of the most relevant alleles by component and time.

P.S. pretty happy this graph was not available in 1940.....

 

[Angela]

We already knew that the blonde hair was picked up by the steppe people from the farmers they first encountered as they exited the steppe, so makes sense to me.

As for the north/south clines I discussed, they don't need to frame it in those terms. All you have to know is that Southern Europeans have more EEF than Northerners, and you can draw the conclusions.

I'm not sure what to think about the statement that "mood disorders" are more prevalent on the EEF genetic background. Depression has been shown again and again to be on a north/south cline, with much more in Northern Europe than Southern Europe. Unless that isn't considered a "mood disorder"? I'm surprised that depression isn't on the graph.

Anxiety is different, although again whether you'd call that a mood disorder or not I don't know. I didn't need this graph to know that anxiety, i.e. "worrying" is more prevalent in Southern Europeans than Northern Europeans.

Bi-polar disorder is definitely a mood disorder, so I would have expected to see it on the graph if they're going to make statements like that.

We already knew that WHG (perhaps also EHG?) is correlated with obesity, so that would explain different clines in Europe.

The facial aging characteristic also makes sense to me.

I don't understand why you think these results would have been a problem in 1940, for Southern Europeans, presumably. I thought the ubermensch should be the ones who would have a longer life span, yes? If it's height you're considering, the Nazis didn't need charts like these to tell them that generally, northern Europeans are taller than Southern Europeans.

 

[Bergin]

did not know that steppe picked up blonde hair from the farmers, I suppose todays higher frequencies in the north are due to positive enviromental selection (and the opposite in the south).

just for semantics, but I agree that the south is more 'temperamental' and the north more 'contained'. in the extremes you can get bipolar and depression, maybe.

 

[Silesian]

Anyone know if Yamnaya picked up their blonde hair (KlTLG gene)from Eurasian Steppe, East Siberia(ANE)?

 

[Angela]

did not know that steppe picked up blonde hair from the farmers, I suppose todays higher frequencies in the north are due to positive enviromental selection (and the opposite in the south).
just for semantics, but I agree that the south is more 'temperamental' and the north more 'contained'. in the extremes you can get bipolar and depression, maybe.

Also, these steppe and farmer admixed people carried these blonde hair genes to areas in the north which were either uninhabited or had small population numbers, so the impact would be greater. Then environmental selection might kick in.

What I find interesting is that only the farmers in that Central European area seem to have depigmented. It wasn't true of Greek Neolithic, for example, or Spanish or Italian Neolithic.

I've always had this gut instinct that it has something to do with heavy consumption of dairy products from cows in farming cultures in central and central/eastern Europe. Somehow the two are related, I think, although I don't precisely know how.

 

[real expert]

We already knew that the blonde hair was picked up by the steppe people from the farmers they first encountered as they exited the steppe, so makes sense to me.

Well, Reich, Hanel, and Carlberg concluded that Yamnaya/Steppe folks got their genes for blondism from their ANE ancestry.

And, as I understand this current paper the authors suggest 2 sources for the contribution of blond- hair for Europeans - Yamnaya/Steppe folks and Anatolian farmers.

Likewise, European hunter gatherers are genetically predicted to have dark skin pigmentation and dark brown hair 9,10,17,18,115–118, and indeed we see that the WHG, EHG and CHG components contributed to these phenotypes in present-day individuals whereas the Yamnaya and Anatolian farmer ancestry contributed to light brown/blonde hair pigmentation (Supplementary Note 2g).

 

[real expert]

Interestingly to note, this study suggests, unlike the previous ones, that the difference in height between Northern and Southern Europeans is not due to selection but because of differential ancestry.

Taken together, these analyses help to settle the famous discussion of selection in Europe relating to height 8,109,114. The finding that steppe individuals have consistently high genetic values for height (Supplementary Note 2c), is mirrored by the UK Biobank results, which find that the ‘Steppe’ ancestral components (Yamnaya/EHG) contributed to increased height in present-day populations (Supplementary Note 2g). This shows that the height differences in Europe between north and south may not be due to selection in Europe, as claimed in many previous studies, but may be a consequence of differential ancestry.

 

[MOESAN]

Interestingly to note, this study suggests, unlike the previous ones, that the difference in height between Northern and Southern Europeans is not due to selection but because of differential ancestry.

more than a way to select: natural pressure (environment diet...) but also social structure and competition maybe based on warlike trends (few males capting a lot of females...) - so differential ancestry and selection are by no way opposed.

 

[Angela]

more than a way to select: natural pressure (environment diet...) but also social structure and competition maybe based on warlike trends (few males capting a lot of females...) - so differential ancestry and selection are by no way opposed.

Agree, especially given the level of warfare documented on the steppe, and the death of so many y lineages.

If you're selecting for height and brawn and quick reflexes, then when you move to a new area it seems as if it's all about ancestry. The selection came first.

 

[Angela]

Some interesting stuff in here now that I actually took the time to read it.

The timing is interesting here. 1000 years ago is approximately plague times. Perhaps that was a factor?

"In contrast, the signal of selection at C2 (rs9267677; p= 9.82e-14; s= 0.04463), also found within this sweep, and associated with psoriasis risk in UK Biobank (p=4.1e-291; OR=2.2) 45,46, shows a gradual increase in frequency beginning c. 4,000 years ago, before rising more rapidly c. 1,000 years ago. This locus might provide a good example of the hypothesis that the high prevalence of auto-immune diseases in modern populations may, in part, be due to genetic trade-offs by which selection increasing the defence against pathogens also have the pleiotropic effect of increasing susceptibility to auto-immune diseases 47,48.

Differences in obesity levels are not just down to diet. As always, nothing is ever that simple.

"Beyond patterns of genetic change at the Mesolithic-Neolithic transition, much genetic variability observed today reflects high genetic differentiation in the hunter-gatherer groups that eventually contributed to modern European genetic diversity 34. Indeed, a substantial number of loci associated with cardiovascular disease, metabolism and lifestyle diseases trace their genetic variability prior to the Neolithic transition, to ancient differential selection in ancestry groups occupying different parts of the Eurasian continent (Supplementary Note 2d). These may represent selection episodes that preceded the admixture events described above, and led to differentiation between ancient huntergatherer groups in the late Pleistocene and early Holocene. One of these overlaps with the SLC24A3 gene which is a salt sensitivity gene significantly expressed in obese individuals 71,72. Another spans ROPN1 and KALRN, two genes involved in vascular disorders 73–75. A further region contains SLC35F3, which codes for a thiamine transport and has been associated with hypertension in a Han Chinese cohort 76,77. Finally, there is a candidate region containing several genes (CH25H, FAS) associated with obesity and lipid metabolism 78–80 and another peak with several genes (ASXL2, RAB10, HADHA, GPR113) involved in glucose homeostasis and fatty acid metabolism 81–90. These loci predominantly reflect ancient patterns of extreme differentiation between Eastern and Western Eurasian genomes, and may be candidates for selection after the separation of the Pleistocene populations that occupied different environments across the continent (roughly 45,000 years ago 91)."

One of those unexpected surprises in genetics research:
"Additionally, our results provide unprecedentedly detailed information about the duration and geographic spread of these processes (Fig. 2) suggesting that an allele associated with lighter skin was selected for repeatedly, probably as a consequence of similar environmental pressures occurring at different times in different regions. In the ancestry-stratified analysis, all marginal ancestries show broad agreement at the SLC45A2 locus (Fig. 2) but differ in the timing of their frequency shifts. The ANA ancestry background shows the earliest evidence for selection, followed by EHG and WHG around c. 10,000 years ago, and CHG c. 2,000 years later. In all ancestry backgrounds except WHG, the selected haplotypes reach near fixation by c. 3,000 years ago, whilst the WHG haplotype background contains the majority of ancestral alleles still segregating in present-day Europeans. This finding suggests that selection on this allele was much weaker in ancient western hunter-gatherer groups during the Holocene compared to elsewhere. We also detect strong selection at the SLC24A5 locus (rs1426654; p=6.45e-09; s=0.019) which is also associated with skin pigmentation 65,70. At this locus, the selected allele increased in frequency even earlier than SLC45A2 and reached near fixation c. 3,500 years ago (Supplementary Note 2a). Selection on this locus thus seems to have occurred early on in groups that were moving northwards and westwards, and only later in the Western hunter-gatherer background after these groups encountered and admixed with the incoming populations."

Just a note to say that genes from these ancestral groups are in all Europeans, so we're not talking about a wall, but a cline based on differential percentages. I didn't mean to suggest otherwise.

The information on Alzheimer's is a good example. Yes, it's not on the Anatolian farmer background, and yes, the percentages are highest in Northeastern Europe, but my aunt suffered from it. (I was relieved to see that I don't have at least one of the most common markers, and I don't see any signs of it yet at all, whereas we could see it in my aunt already by my age.) Also, my husband's Neapolitan grandmother had it.

So, don't get complacent, and look at recent family history, imo, rather than studies like this, in terms of problems to monitor.

Also, some of these results remind me of ones from psychology papers where they just seem to prove what everyone already knew.

No surprise to me that higher Anatolian farmer might mean more anxiety and more irritability, two of my biggest character flaws. There's a reason you hear so often in Italian conversation, "Con calma, per piacere", or why we're constantly telling each other to have patience. It's because it comes HARD for a lot of us.

At this stage of my life my reserves of it are completely gone; I used it all up on my children and husband. I have none left for anyone else, and I had precious little at any time for "slow" people; slow thinking, slow talking, slow moving. I would practically bite through my lip or tongue to stop myself from lashing out, and still do. I can still move and work faster than people half my age or more. We went out to lunch today and it was just maddening to watch the waiters and waitresses strolling around to set and prep the tables as if they had all the time in the world. My restaurateur uncles would have blistered their ears with the shouting and cursing, and they were normally quiet, reserved men. I've always thought that this tendency toward anxiety and irritability plays a factor in how few children Italians have these days; when I would see those Irish families at church with 7 or 8 children I would think, Thank God for birth control; I'd shoot myself if I had to deal with that.

 

[Jovialis]

Sorry, out of juice.

Interesting paper. I'll read it later.

Do they differentiate in the paper between diseases like bi-polar disorder and depression? I ask, because papers on modern populations find a difference in frequency south to north, with bi-polar disorder on a south/north cline, and depression on a north/south cline.

I think that makes a lot of sense simply based on my own anecdotal observations. There's certainly shades of those psychological traits regarding northern vs southern Europeans.

 

[Jovialis]

The 1940s comment doesn't make sense to me either. How would Hitler, an Austrian and the south Germans of whom were the most committed Nazis feel about being more intermediate between Nordics and southern Europeans, and higher in farmer ancestry to northern Germans and Scandinavians?

 

[Angela]

The 1940s comment doesn't make sense to me either. How would Hitler, an Austrian and the south Germans of whom were the most committed Nazis feel about being more intermediate between Nordics and southern Europeans, and higher in farmer ancestry to northern Germans and Scandinavians?

Yeah, maybe he can explain what he means.

OK, northerners on average are taller than southerners, but that means exactly what it says: on average. My husband is 6 feet tall, my son 6 feet 2 inches. What was Hitler? 5'9" on a good day? Most southern Germans aren't very tall; neither are British people. Montenegrins are VERY tall. Big whoops.

Southerners are prone to certain diseases or traits more than northerners, but northerners have their own set of disadvantageous traits and disease risks.

I don't think ubermenschen should be prone to diabetes, or Alzheimers, or clinical depression.

The whole thing was a joke anyway. Hitler made Italians honorary Aryans because he loved Mussolini and the fascism he invented. At the same time, it was far easier to hide Jews in Italy than in Poland, because Jews look Southern European. As is the case with political discourse today, much of it makes absolutely no logical sense.

What should concern people, or at least Jews, is that any commercial dna test can tell you whether you have Ashkenazi ancestry and how much. If some of these Neo Nazi lunatics in eastern European countries take over, the few Jews remaining should leave before they force people to test. In fact. if I were Jewish I would leave Europe altogether right now. I don't think leopards change their spots. In economic hard times people always need a scapegoat. I'd go sit in Israel and contribute to its remarkable accomplishments. Let the Arab League rant and rave. Having a nuclear weapon is a complete deterrent. You won't drive us into the sea. We'll nuke you first.

 

[Archetype0ne]

Very interesting paper. A breath of fresh air from the unipaternal marker discussions.

As for what Berger meant, I think it has something to do with the claim that certain traits are inherited rather than selected? (Not entirely sure how that works, and where is the fine line, since the two are interconnected). I personally doubt this paper would even be noticed in the 1930s, given eugenics was at its peak, and claims such as the above were considered axioms. <- This is in no way meant to take anything from this paper.

Anyways, for me such papers touch deeper topics, at the heart of nature vs nurture. Sure height and other traits are the first thing one sees and important, but depression and mood disorders directly remove a degree of freedom from free will, limiting it to a narrower scope. As the Bavarians say: we are who we are. But maybe advances in science and technology will restitute the layers of freedom back to the individual. Needless to say, I welcome more papers like this.

 

[Bergin]

the 1940 comment: maybe it was just a wrong one.
anyway, I was not talking about the intrinsic information, which is relatively balanced.
I was talking about the presentation of the data: specifically it looks as if they are ranked following the trend of the farmers. Lower in the first half and higher in the second. it highlights the differencr from the UberM.
anyway, maybe it was a stupid comment

 

[Silesian]

So many interesting mutations that make us individually unique. Science is just beginning to understand the differences in health. Hopefully the pseudoscience of applying identical therapies (or mix and matching different vaccines at the same time without knowing risk assessment)across the board in pandemics will be addressed, as certain genes and mutations confer immunity (CCR5-Delta32 -one example/another example/some react to COVID-19//and or vaccines differently)to different diseases.

 

[MOESAN]

marginally
- I don't see how oppose selection to genetic heritage: selection acts upon heritage, and heritage seems and really is rather stable when selection forces don't change. Or I miss something?
- It seems longevity is a bit longer among southern Europeans, spite a poorer lifestyle at first sight. Diet is at play, but when we consider the higher heritage of steppic DNA among northerners, may we not imagine their ancient warlike habits could have selected genes for strength, combativity, agressivity at the depends of longevity? The most often you have to fight to survive, the less sure your theorical longevity potential is the most important thing? Just a lod voice reflexion? I am not going to put too much on it.

 

[Angela]

So many interesting mutations that make us individually unique. Science is just beginning to understand the differences in health. Hopefully the pseudoscience of applying identical therapies (or mix and matching different vaccines at the same time without knowing risk assessment)across the board in pandemics will be addressed, as certain genes and mutations confer immunity (CCR5-Delta32 -one example/another example/some react to COVID-19//and or vaccines differently)to different diseases.

The sad thing is that we're accumulating all this knowledge and yet the Woke mentality so prevalent in academia and even medicine ensures that it won't be used to target therapies of any kind.

In fact I worry that there won't even be the funding for the papers themselves.

I was already reading papers about differences in psychiatric traits from individual to individual but also from group to group based on heredity years ago. It supported all the wisdom of my elders that I would hear as I sat at their feet. Stories like why my great-aunt was forbidden to marry into family X, because alone in the town they turned out a drunkard in every generation, for example.

It's not culture, or rather it's culture stemming from genetic differences that creates a situation where apparently the Finns have a loved word describing how great it is to go home and get drunk in your underwear. They used it for a tourist campaign, which begs the question of why you'd want to go to Finland if all you wanted to do was sit in a hotel room in your underwear and get drunk! Surely you could do that at home, and save the airfare and hotel fees! During the pandemic it came out that a huge percentage of people in countries in far northern Europe are people living alone.

Saying such a thing would be inconceivable in Italy. Likewise, I've seen the reactions of people from the extreme north when they visit Italy. Some of them are very uncomfortable with the way we sort of "clump together", if you know what I mean. I always brought boyfriends to family gatherings when I was dating. If they didn't like all the aunts and uncles and cousins and their children hugging and kissing and chattering away, I didn't date them any more. Hence my southern Italian husband, even though his family were on another level still, and required some getting used to!

Unfortunately, what I also started reading were the multiple papers showing how large a percentage of the prison population, and thus probably of the people I was trying to put there, had serious psychiatric illnesses. One psychiatrist, not long after WWII, when such breaches of standard practices went on, put a bit of lithium into the prison water supply. There was a drastic cut in prison violence, rapes, riots, etc.

So, what did that say about personal responsibility, about free will generally? Certainly, some people cannot be allowed to move freely in society, because it's just too dangerous for the rest of us. Take child molesters, for example. They have the highest known level of recidivism. They CANNOT be let out. Yet, does anyone doubt this is a serious illness. However, I've been exposed to them; these are REALLY sick people.

Shouldn't we as a society be trying to figure out what is wrong in some people's "wiring", and how to fix it, rather than just incarcerating people and letting them brutalize each other in prison?

Anyway, that's one of the reasons I went from criminal law to real estate and contract law. It didn't sit right ethically. Nor did being a defense lawyer and trying to get these people off. Not to mention that dealing with such people day in day out sucks the soul right out of you if you are at all a feeling and emotional person.