Adaptation in UK pop at genes influencing blood pressure reveal pop structureAnalyzin

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Nick Patterson and some other people at Harvard have previewed a new paper where they compare modern UK autosomal data with the ancient samples which have become available, and reach some interesting conclusions.

See:
http://biorxiv.org/content/biorxiv/early/2016/05/27/055855.full.pdf

Population structure of UK Biobank and ancient Eurasians reveals adaptation at genes influencing blood pressure

"Analyzing genetic differences between closely related populations can be a powerful way to detect recent adaptation. The very large sample size of the UK Biobank is ideal for detecting selection using population differentiation, and enables an analysis of UK population structure at fine resolution. In analyses of 113,851 UK Biobank samples, population structure in the UK is dominated by 5 principal components (PCs) spanning 6 clusters: Northern Ireland, Scotland, northern England, southern England, and two Welsh clusters. Analyses with ancient Eurasians show that populations in the northern UK have higher levels of Steppe ancestry, and that UK population structure cannot be explained as a simple mixture of Celts and Saxons. A scan for unusual population differentiation along top PCs identified a genome-wide significant signal of selection at the coding variant rs601338 in FUT2 (𝑝 = 9.16 × 10−9). In addition, by combining evidence of unusual differentiation within the UK with evidence from ancient Eurasians, we identified new genome-wide significant (𝑝 < 5 × 10−8) signals of recent selection at two additional loci: CYP1A2/CSK and F12. We detected strong associations to diastolic blood pressure in the UK Biobank for the variants with new selection signals at CYP1A2/CSK (𝑝 = 1.10 × 10−19) and for variants with ancient Eurasian selection signals in the ATXN2/SH2B3 locus (𝑝 = 8.00 × 10−33), implicating recent adaptation related to blood pressure."

One interesting thing they did is "To identify the populations underlying the 6 clusters, we projected the PoBI dataset20, comprising 2,039 samples from 30 regions of the UK, onto the UK Biobank PCs (Figure 2, Supplementary Figure 3). The individuals in the PoBI study were from rural areas of the UK and had all four grandparents born within 80 km of each other, allowing a glimpse into the genetics of the UK before the increase in mobility of the 20th century."

Also, "Modern European populations are known to have descended from three ancestral populations: Steppe, Mesolithic Europeans and Neolithic farmers21,22. We projected ancient samples from these three populations as well as ancient Saxon samples24 onto the UK Biobank PCs (Figure 3, Supplementary Figure 4, see Online Methods). These populations were primarily differentiated along PC1 and PC3, indicating higher levels of Steppe ancestry in northern UK populations."

From the body of the paper:

"We consistently obtained significantly positive 𝑓4 statistics, implying that both the modern Celtic samples and the ancient Saxon samples have more Steppe ancestry than the modern Anglo-Saxon samples from southern and eastern England. This indicates that southern and eastern England is not exclusively a genetic mix of Celts and Saxons. There are a variety of possible explanations, but one is that the present genetic structure of Britain, while subtle, is quite old, and that southern England in Roman times already had less Steppe ancestry than Wales and Scotland."

Southern and Eastern England is the largest genetic cluster in the U.K. and has the least steppe ancestry, and they seem to think it's likely that this was already the case in Roman times. That's contrary to the position of the Hellenthal group, which is fine with me, because some of their work makes no sense to me in light of what we know from history.

So, the obvious question is why? Could the Belgae have been a more "southern" leaning group? Could it be the Romans? If it increased later, then the Normans are a possibility, an idea which Dienekes seems to favor.
http://dienekes.blogspot.com/2016/05/british-celts-have-more-steppe-ancestry.html

Btw, they make an interesting point about the Welsh:
"Additionally, the lack of any ancient sample correlation with PC2 suggests that Welsh populations are not differentially admixed with any ancient population in our data set, and likely underwent Welsh-specific genetic drift."

What do you guys think about that? That would mean that the Anglo-Saxon admixture went right through the mountains to the west coast. I don't know that I buy that given the differences in yDna.
 
If the Belgae were the cause the Welsh should also have less Steppe ancestry. Larger Neolithic survival, perhaps? Take for instance this map: Affinity of Rathlin Irish bell Beakers:

Affinities.png
 
If the Belgae were the cause the Welsh should also have less Steppe ancestry. Larger Neolithic survival, perhaps? Take for instance this map: Affinity of Rathlin Irish bell Beakers:

Affinities.png

Only thing is doesn't it look as if the Neolithic people actually survived a little less in England rather than more. Maybe it's my eyes paying tricks on me, but it seems as if Ireland and Scotland are a tiny bit more orange. Southern and Eastern England are definitely less British Bronze Age, though.

I don't understand it. My knowledge of this period in England is not very detailed. Did the Belgae settle in Wales and Scotland, though? Were there other pre-Roman migrations from Gaul that would explain it? Someone very conversant with the particular tribes that moved into Britain in, say, the first millennium BC might be able to explain it.

The comments about the Welsh seem a little unlikely to me. There is definitely a cline in the yDna, with the west having a great deal less yDna "I", even after the migrations over the centuries from England proper into Wales. Also, there's definitely a difference for Wales in terms of the Hungarian Bronze Age.

http://www.pnas.org/content/113/2/368/F3.large.jpg

F3.large.jpg
 
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I'm seeing commentary that the authors of the paper are putting this down to Roman era admixture. That's not at all the case from what I can see. That was the Hellenthal group.

Again, from the paper:
"There are a variety of possible explanations, but one is that the present genetic structure of Britain, while subtle, is quite old, and that southern England in Roman times ALREADY had less Steppe ancestry than Wales and Scotland."

As I said, it doesn't look Neolithic to me, based on both the map and the fact they would have fled to refuge areas, so it's either pre-Roman era migrations from the continent, or they're wrong about the timing, and it came later, in which case both Romans and Normans are a possibility, and not just Normans, but people from all over France during the medieval era when the ties between the two countries were very strong.
 
Nick Patterson and some other people at Harvard have previewed a new paper where they compare modern UK autosomal data with the ancient samples which have become available, and reach some interesting conclusions.

See:
http://biorxiv.org/content/biorxiv/early/2016/05/27/055855.full.pdf

Population structure of UK Biobank and ancient Eurasians reveals adaptation at genes influencing blood pressure

"Analyzing genetic differences between closely related populations can be a powerful way to detect recent adaptation. The very large sample size of the UK Biobank is ideal for detecting selection using population differentiation, and enables an analysis of UK population structure at fine resolution. In analyses of 113,851 UK Biobank samples, population structure in the UK is dominated by 5 principal components (PCs) spanning 6 clusters: Northern Ireland, Scotland, northern England, southern England, and two Welsh clusters. Analyses with ancient Eurasians show that populations in the northern UK have higher levels of Steppe ancestry, and that UK population structure cannot be explained as a simple mixture of Celts and Saxons. A scan for unusual population differentiation along top PCs identified a genome-wide significant signal of selection at the coding variant rs601338 in FUT2 (������ = 9.16 × 10−9). In addition, by combining evidence of unusual differentiation within the UK with evidence from ancient Eurasians, we identified new genome-wide significant (������ < 5 × 10−8) signals of recent selection at two additional loci: CYP1A2/CSK and F12. We detected strong associations to diastolic blood pressure in the UK Biobank for the variants with new selection signals at CYP1A2/CSK (������ = 1.10 × 10−19) and for variants with ancient Eurasian selection signals in the ATXN2/SH2B3 locus (������ = 8.00 × 10−33), implicating recent adaptation related to blood pressure."

One interesting thing they did is "To identify the populations underlying the 6 clusters, we projected the PoBI dataset20, comprising 2,039 samples from 30 regions of the UK, onto the UK Biobank PCs (Figure 2, Supplementary Figure 3). The individuals in the PoBI study were from rural areas of the UK and had all four grandparents born within 80 km of each other, allowing a glimpse into the genetics of the UK before the increase in mobility of the 20th century."

Also, "Modern European populations are known to have descended from three ancestral populations: Steppe, Mesolithic Europeans and Neolithic farmers21,22. We projected ancient samples from these three populations as well as ancient Saxon samples24 onto the UK Biobank PCs (Figure 3, Supplementary Figure 4, see Online Methods). These populations were primarily differentiated along PC1 and PC3, indicating higher levels of Steppe ancestry in northern UK populations."

From the body of the paper:

"We consistently obtained significantly positive ������4 statistics, implying that both the modern Celtic samples and the ancient Saxon samples have more Steppe ancestry than the modern Anglo-Saxon samples from southern and eastern England. This indicates that southern and eastern England is not exclusively a genetic mix of Celts and Saxons. There are a variety of possible explanations, but one is that the present genetic structure of Britain, while subtle, is quite old, and that southern England in Roman times already had less Steppe ancestry than Wales and Scotland."

Southern and Eastern England is the largest genetic cluster in the U.K. and has the least steppe ancestry, and they seem to think it's likely that this was already the case in Roman times. That's contrary to the position of the Hellenthal group, which is fine with me, because some of their work makes no sense to me in light of what we know from history.

So, the obvious question is why? Could the Belgae have been a more "southern" leaning group? Could it be the Romans? If it increased later, then the Normans are a possibility, an idea which Dienekes seems to favor.
http://dienekes.blogspot.com/2016/05/british-celts-have-more-steppe-ancestry.html

Btw, they make an interesting point about the Welsh:
"Additionally, the lack of any ancient sample correlation with PC2 suggests that Welsh populations are not differentially admixed with any ancient population in our data set, and likely underwent Welsh-specific genetic drift."

What do you guys think about that? That would mean that the Anglo-Saxon admixture went right through the mountains to the west coast. I don't know that I buy that given the differences in yDna.

I tend to agree with Dienekes and had suggested the same when looking at Admixtures scores of various English groups. Both sides of my family are overwhelmingly South England, and on Admixture, our West Mediterranean is considerably higher than Irish, Scottish and northern English groups. I suspect it is due to additional Norman and post-Norman immigration to England via France. A lot of William's men who were granted lands in England must have been local French nobles who were not directly descended from north men, at least not in recent times. The question then becomes, why would the French population of 1000 AD or earlier be shifted towards SW or S Europe? Was there less of a Neolithic collapse in SW Europe than Germany? Perhaps resulting in additional "farmer" like ancestry in France?
 
Aaron1981: The question then becomes, why would the French population of 1000 AD or earlier be shifted towards SW or S Europe? Was there less of a Neolithic collapse in SW Europe than Germany? Perhaps resulting in additional "farmer" like ancestry in France?

That's what I've always thought given the data. Look at the difference between the southwest French percentages and the English percentages as visualized here in the Haak chart, which remember is not an admixture analysis. If they broke out southeast France it would be the same. There's even a difference between the "French" numbers, which are really the northern half of the country, extending a little bit into the Lyon area, and the English numbers. Then look at the proportions for Orcadians, who are the most "steppic" of the Celtic "fringe" group, I think.

https://f.hypotheses.org/wp-content...h-Linguistic-and-Historical-Origins-Added.png

Haak-et-al-2015-Figure-3-Admixture-Proportions-in-Modern-DNA-With-Linguistic-and-Historical-Origins-Added.png


Ralph and Coop came to the same conclusion about later migrations by using IBD analysis:

http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1001555

"On the other hand, we find that France and the Italian and Iberian peninsulas have the lowest rates of genetic common ancestry in the last 1,500 years (other than Turkey and Cyprus), and are the regions of continental Europe thought to have been least affected by the Slavic and Hunnic migrations. These regions were, however, moved into by Germanic tribes (e.g., the Goths, Ostrogoths, and Vandals), which suggests that perhaps the Germanic migrations/invasions of these regions entailed a smaller degree of population replacement than the Slavic and/or Hunnic, or perhaps that the Germanic groups were less genealogically cohesive. This is consistent with the argument that the Slavs moved into relatively depopulated areas, while Gothic “migrations” may have been takeovers by small groups of extant populations [54],[55]."

I find them more persuasive than the Hellenthal group.

Also, I don't know that I'd put the limit at 1000 AD. English kings married French queens, and there was mixing of the aristocracies as well all through the Middle Ages and later.* Retinues came with them, including soldiers. Aquitaine in particular was held for a very long time. It might have had some impact.

I'm not saying I'm sold on all of this. There[s a lot of possibilities, as the authors acknowledge. Who knows, maybe the Broad Institute has some ancient sample from southern England which is slightly different from the more northern Bronze Age samples, and just doesn't want to reveal it yet. Even if that were true, it wouldn't negate that some small changes occurred later on, of course.

*There's a very interesting history by Barbara Tuchman mainly about a nobleman of the Middle Ages, Enguerrand de Coucy, which makes the point that he wouldn't have understood the distinction of French versus English in relation to himself.
https://en.wikipedia.org/wiki/A_Distant_Mirror
 
South English have much of Mediterranean ancestry that is neither Celtic nor Germanic

Study linked below says that both Pre-Roman Celts and Early Anglo-Saxon immigrants had less of Southern European ancestry than modern English, which means that modern English are not just a Celtic-Germanic mix but that some other admixture is pulling them genetically towards the South:

http://biorxiv.org/content/biorxiv/early/2016/05/27/055855.full.pdf

Excerpt:

We analyzed a variety of samples from Celtic (Scotland and Wales) and Anglo-Saxon (southern and eastern England) populations from modern Britain in conjunction with the PoBI samples and ancient Saxon samples from eastern England24 in order to assess the relative amounts of Steppe ancestry. We computed statistics27 of the form, where Steppe and Neolithic Farmer populations are from ref. 21,22 , Pop1 is either a modern Celtic or ancient Saxon population and Pop2 is a modern Anglo-Saxon population (Table 2, Supplementary Table 2). This statistic is sensitive to Steppe ancestry with positive values indicating more Steppe ancestry in Pop1 than Pop2. We consistently obtained significantly positive statistics, implying that both the modern Celtic samples and the ancient Saxon samples have more Steppe ancestry than the modern Anglo-Saxon [they mean: English] samples from southern and eastern England. This indicates that southern and eastern England is not exclusively a genetic mix of Celts and Saxons. There are a variety of possible explanations, but one is that the present genetic structure of Britain, while subtle, is quite old, and that southern England in Roman times already had less Steppe ancestry than Wales and Scotland.

In other words, both Iron Age Celts and Anglo-Saxon immigrants were more Northern genetically than are modern English.

This is also obvious if you compare them in any of Gedmatch calculators, for example Eurogenes K15:

http://eurogenes.blogspot.com/2014/10/hinxton-ancient-genomes-roundup.html

1) Hinxton Iron Age Celtic Briton - 38% North Sea / 30% Atlantic / 6.5% Mediterranean

2) Hinxton Early Anglo-Saxon - 41.5% North Sea / 28.5% Atlantic / 6.5% Mediterranean

3) Modern Englishman from Kent - 35.5% North Sea / 30% Atlantic / 11.5% Mediterranean

Modern Englishman scores almost two times more of Mediterranean than both Pre-Roman Celt and Anglo-Saxon immigrant.

Also North Sea admixture is lower in modern English from southern England than in both Celts and original Anglo-Saxons.

======================

This Southern admixture must be either from Roman times or from Post-Anglo-Saxon (e.g. Norman and later) times.
 
This may be too simple an explanation, but wouldn't it make sense for Neolithic immigrants to mainly populate southeastern Englang, because it's more suited to farming? Later waves (i.e. IE) would have had more 'exclusivity' in less suited regions (like Wales) and show up bigger there.
 
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couldn't there be biass, taking only Hinxton as a reference for both Iron Age Celtic Briton and Early Anglo-Saxon ?
 
The paper is already discussed here:
http://www.eupedia.com/forum/thread...e-reveal-pop-structureAnalyzin?highlight=POBI

In fact, I should probably merge the threads.

The paper specifically says that the change occurred prior to the Roman era.
"There are a variety of possible explanations, but one is that the present genetic structure of Britain, while subtle, is quite old, and that southern England in Roman times already had less Steppe ancestry than Wales and Scotland."
 
Southern and Eastern England is the largest genetic cluster in the U.K. and has the least steppe ancestry, and they seem to think it's likely that this was already the case in Roman times. That's contrary to the position of the Hellenthal group, which is fine with me, because some of their work makes no sense to me in light of what we know from history.

So, the obvious question is why? Could the Belgae have been a more "southern" leaning group? Could it be the Romans? If it increased later, then the Normans are a possibility, an idea which Dienekes seems to favor.
South/East England is top farming land in GB. Population of EEF farmers were always highest there. As such, IE newcomers mixed with EEF in bigger proportions, shedding more Steppe admixture than anywhere in GB. Also for the same agrarian reason, which denotes wealth, Romans and other South Europeans settled here during Roman period.
 
Only thing is doesn't it look as if the Neolithic people actually survived a little less in England rather than more. Maybe it's my eyes paying tricks on me, but it seems as if Ireland and Scotland are a tiny bit more orange. Southern and Eastern England are definitely less British Bronze Age, though.
I see your point. Let's change EEF in my last post to Late Neolithic population, who was already lower on EEF. And how about a local genetic selection to increase survival in Scotland and Ireland people with higher Steppe admixture, and likewise increases survival with bigger farmer adaptation in S-E England?
 
I see your point. Let's change EEF in my last post to Late Neolithic population, who was already lower on EEF. And how about a local genetic selection to increase survival in Scotland and Ireland people with higher Steppe admixture, and likewise increases survival with bigger farmer adaptation in S-E England?

It's possible, but isn't it more parsimonious to posit that perhaps the Belgae and other first millennium BC migrations from the continent had more "southern" admixture by that time? Of course we won't know until we have more samples from them.

Or, as I mentioned above, maybe the timing is off, and it actually is Roman era and later. We're certainly finding quite a few non-local burials in England, and from the time of the Conqueror on you have lots of people from the continent emigrating to Britain, and most of those people might not have made it to Scotland or Ireland.

It needn't be a mass migration in any case. If we use the calculator results posted by Tomenable, we're talking about a change from 6% to 9% in "Mediterranean".
 
Interesting paper. I am not surprised by the higher Steppe ancestry among Celtic populations for three reasons:

1) They have higher R1b levels, which we know came in one major migration event (R1b-L21) in the Early Bronze Age, straight from Central Europe (only a few centuries after R1b appears in Germany c. 2500 BCE) to Ireland (c. 2000 BCE) via Britain (c. 2200 BCE).

2) Scotland already scored highest for Gedrosian ancestry at the Dodecad K12b, which I have long argued represents Steppe ancestry linked to R1b tribes.

3) England was settled by a variety of peoples who all had slightly (Anglo-Saxons, Danes, Normans) or considerably lower (Romans) levels of Steppe admixture than the Celts. I don't think that the Belgae were very different from the Insular Celts in that regard though.


Btw, they make an interesting point about the Welsh:
"Additionally, the lack of any ancient sample correlation with PC2 suggests that Welsh populations are not differentially admixed with any ancient population in our data set, and likely underwent Welsh-specific genetic drift."

What do you guys think about that? That would mean that the Anglo-Saxon admixture went right through the mountains to the west coast. I don't know that I buy that given the differences in yDna.

I think what they meant is that:

1) The Welsh did not inherit much DNA from the Romano-British population that fled from the Anglo-Saxons. In other words, they are not the descendants of Roman-era Englanders, but the mostly the direct descendants of Roman-era Wales.

2) The difference between northern and southern Welsh was caused by a genetic drift due to the lack of regular intermarriages between the two populations.
 
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The selection for polymorphisms of rs601338 in FUT2 is related to Noro-virus resistance (the one tested by 23andMe). It's not very interesting in terms of historical population movements, but it does tell us that this virus was probably more common in some regions, or at least that the locals needed a genetic immunity to it because it frequently caused infantile deaths in some (poorer, less well nourished?) populations.

The variations within the CYP1A2 (synthesis of cholesterol, steroids and other lipids; blood pressure, inflammation responses, tumour cell growth), CSK (cell growth, immune response) and F12 (blood clotting) genes sound more interesting, but I will have to read the paper in detail. At first sight they don't seem to mention the correlation of any of these with specific populations.
 
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We've discussed this paper before, but now it's officially out, and it might indicate how a slight southern shift might have occurred in the people of southern/souteastern England during the Roman era.

See:
[h=1]Going south of the river: A multidisciplinary analysis of ancestry, mobility and diet in a population from Roman Southwark, London[/h]http://www.sciencedirect.com/science/article/pii/S0305440316301030

"First application of macromorphoscopics to determine ancestry in Roman Britain.
•Isotopic and morphological evidence point to connections with the southern Mediterranean.
•This is the first identification of people with African and Asian ancestry in Roman London.


[h=2]Abstract[/h]This study investigated the ancestry, childhood residency and diet of 22 individuals buried at an A.D. 2nd and 4th century cemetery at Lant Street, in the southern burial area of Roman London. The possible presence of migrants was investigated using macromorphoscopics to assess ancestry, carbon and nitrogen isotopes to study diet, and oxygen isotopes to examine migration. Diets were found to be primarily C[SUB]3[/SUB]-based with limited input of aquatic resources, in contrast to some other populations in Roman Britain and proximity to the River Thames. The skeletal morphology showed the likely African ancestry of four individuals, and Asian ancestry of two individuals, with oxygen isotopes indicating a circum-Mediterranean origin for five individuals. Our data suggests that the population of the southern suburb had an ongoing connection with immigrants, especially those from the southern Mediterranean."
 
couldn't there be biass, taking only Hinxton as a reference for both Iron Age Celtic Briton and Early Anglo-Saxon ?

Oakington samples also had less of Mediterranean admixture in Eurogenes K15 than modern English.

I would like to see the results of those samples from Roman-era Eburacum. How much did they score?
 

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