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Sunday, March 15, 2015

Eight thousand years of natural selection in Europe


Update 11/10/2015: Eight thousand years of natural selection in Europe - take 2

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A new preprint at bioRxiv reports on the first genome-wide scan for selection using ancient DNA, with a couple of unexpected outcomes:

The SNP (rs4988235) responsible for lactase persistence in Europe gives the strongest signal in our analysis. We estimated the selection coefficient on the derived allele to be 0.015 (95% confidence interval; CI=0.010-0.034) using a method that fits a hidden Markov model to the population allele frequencies as they change over time. Our data strengthens previous reports of the late appearance of lactase persistence in Europe, with the earliest appearance of the allele in a central European Bell Beaker sample (individual I0112) who lived approximately 4,300 years ago. We detect no evidence of lactase persistence in Early Neolithic farming populations like the Linearbandkeramik (LBK), or in the steppe pastoralist Yamnaya, despite their use of domesticated cattle (Figure 2).
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We find a surprise in seven Scandinavian hunter-gatherers from the Motala site in southern Sweden who lived around 7,700 years before present. While the western hunter-gatherers of central and southern Europe largely have the ancestral allele at the two major European skin pigmentation loci, the closely related Scandinavian hunter-gatherers have both the derived alleles contributing to light skin pigmentation at high frequency (Figure 2B). Thus, the derived allele of SLC24A5 was common in both the Scandinavian hunter-gatherers and Early European farmers, but not in the geographically intermediate western hunter-gatherers. Further, in four out of seven Motala samples, we observe the derived allele of rs3827760 in the EDAR gene, which has effects on tooth morphology and hair thickness. This allele has been the subject of a selective sweep in East Asia, and today it is at high frequency in East Asians and Native Americans.

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The derived allele in the Motala samples lies on the same haplotype as in modern East Asians (Extended Data Figure 4) implying a shared origin. The statistic f4(Yoruba, Scandinavian hunter-gatherers, Han, Onge Andaman Islanders) is significantly negative (Z=-3.9) implying gene flow between the ancestors of Scandinavian hunter-gatherers and Han so this shared haplotype is likely the result of ancient gene flow between groups ancestral to these two populations.

The high frequency of the East Asian-specific EDAR allele among the Motala foragers is even more surprising for me than their inferred light skin. But it does at least gel with the earlier finding that Scandinavian hunter-gatherers did not contribute significant ancestry to modern Europeans (see here).

Citation...

Mathieson et al., Eight thousand years of natural selection in Europe, bioRxiv preprint first posted online March 14, 2015; doi: http://dx.doi.org/10.1101/016477

27 comments:

postneo said...

@Alberto

By "Central Asia" I mostly refer to the region east of the Caspian, though it probably includes neighbouring areas. There seems to be a difference between Turkmenistan/North East Iran (with clear Near Eastern Neolithic influence) and regions further north and east (Uzbekistan, Tajikistan...) where there probably weren't much crops"

http://www.grida.no/graphicslib/detail/population-density-central-asia_30dd

turkmenistan has always been an arid place and has never supported huge populations. As for Uzbekistan, its the south east areas bordering Afghanistan, Tajiks where populations are high. Kazakhstan has low population density as well.


The introduction of livestock and farming here is from the south. David has thrown away some interesting signals from his component. One of the few clearly intrusive signals in Yamnaya and europe is the south asian one. The south asian is diluted by Iranian demographics, which would probably have a little less ASI, ANE and a bit more west asian.

Alberto said...

@postneo

I answered in the previous thread. Here I see that you included a link to population density, but this is from the present, not 6.000 year ago.

Krefter said...

Just because some Motala-HGs had a derived allele in rs3827760 doesn't mean their relatives could not have contributed a significant amount of ancestry to modern Europeans.

There certainly is SHG-like ancestry in Europe, especially in Balts.

Kristiina said...

Before anyone proposes that Swedish Mesolithic EDAR should be assigned to yDNA N, I propose another theory. :-) In the new paper ”Bottleneck in human Y-chromosomes in the last 10,000 years”, there are interesting yDNA trees and Figure S35 gives the phylogeny of yDNA Q. We all know that Native Americans carry EDAR and have yDNA Q, so I would think that EDAR could well have been brought to Scandinavia by yDNA Q. There is for example Q1d L527 which seems to found in Scandinavia and sporadically also elsewhere in Europe. Irrespective of the origin of P, Q1d was probably never in Southeast Asia, so it would be only logical that Swedish Mesolithic hunter gatherers did not have any ENA, e.g. Motala12 K15 averages show that he had 0 Siberian and 0 Southeast Asian but 0.97 Amerindian and 0.25 Oceanian. Then, we also know that one of Motala hunter gatherers was close to be assigned to yDNA Q.

Davidski said...

"There certainly is SHG-like ancestry in Europe, especially in Balts."

And you base this statement on?

Krefter said...

"And you base this statement on?"

On tests you and academics run. Balts aren't Yamna+MNE. They have more WHG than any non-forager ancient genomes do. CWC disputes an argument that says the western Steppe was high in WHG. A very easy answer to this is SHG-like ancestry.

Have you tried SHG+CWC or SHG+BBC for Balts?

jeanlohizun said...

@ Krefter

I checked the ANE/Yamnaya_related ancestry ratio for Lithuanians, Norwegians and Scotts and is about ~0.34 to 0.35 not that different from French or Polish 0.35 each.

Shaikorth said...

@David

Maybe try qpAdm for Lithuanians with the references used for Icelandic to measure the Krefter idea of Motala ancestry?

Motala_HG
Germany_MN
Yamnaya

Icelandic got 0% Motala (I assume the fit you posted was the best), it would be interesting to see how Lithuanians will do.

Alberto said...

Yes, while Motala population might have been short lived in Sweden, they came from somewhere (likely the east Baltic).

Besides, there is no natural border to separate WHG and EHG, so in some area around Belarus there could be a gradient between both extremes. It would be more strange to have a line separating 100% WHG from the 60/40 WHG/ANE EHG.

It would also be interesting to know if EHG from around the Dnieper were like Samara/Karelia ones or had more WHG.

Davidski said...

OK, I ran that test. Just a quick glance at the stats suggests to me that the model was a total failure, so I'm not sure if this means anything, but here you go...

Motala_HG -0.000
Germany_MN 0.422
Yamnaya 0.578

I'll try other models and outgroups to see if I can find something that works in this context.

Shaikorth said...

What are the outgroups? Resorting to chimp, Ju'hoan and Papuan should remove relatedness issue if nothing else works.

postneo said...

@alberto

I read your comment.

Turkmenistan does not have extensive river systems or reservoirs unless I am mistaken.

There seems to be windows of time where kazakh, uzbek and turkmen lands were not arid. These would be opportunities for people from more populated areas to expand.

Early farmers learnt how to tap ground water in the Iranian plateau. Moisture was not an issue in mountainous areas of the south and of course the river systems further south.

Grey said...

"Thus, the derived allele of SLC24A5 was common in both the Scandinavian hunter-gatherers and Early European farmers, but not in the geographically intermediate western hunter-gatherers."

http://www.freeworldmaps.net/asia/asia.jpg

There's a natural geographical "bowl" all the way from the north European plain to Siberia skirting the edge of the more mountainous terrain.

If the bio-regions within that bowl were mostly latitudinal then it's not surprising if adaptations within that bowl stretched over a very wide range.

It does seem to imply though that the SLC24A5 gene wasn't a farmer adaptation but a latitude or other environmental adaptation instead and that the first herders came from a region adjacent to that bowl and picked it up before they expanded with it.

gerschwint T said...

The paper notes a special relationship between Scandinavian HGs (it doesn't specify whether just Motala or all SHGs) and the Han. AFAIK, this has not been noted by anyone else, nor does an 'East Asian' component appear in ADMXITURE runs, except at low K's, which is something it has in common with all West Eurasian HGs. Basically, I'm wondering what the implications of this? If you compare all HG relationships to Han side by side, do the Motala uniquely stand out, and, if so, was this in some way previously thought to be solely ANE?

The article wasn't completely thorough, sadly, so while we can infer no other instances of EDAR were found in any of the other samples (including other Scandinavian samples), it doesn't state this explicitly (only that it was markedly high in Motala).

If Motala genuinely have nothing to distinguish themselves from other European HGs except ANE, then could EDAR originally have been something shared by both early ANE and East Asians, but lost by the time ANE revisited Europe in admixed form via Yamnaya? (For that matter, have MA1 and AG1 and 2 been checked for EDAR?)

German Dziebel said...

@gerschwint T

MA-1 is EDAR-ancestral.

"Motala12 K15 averages show that he had 0 Siberian and 0 Southeast Asian but 0.97 Amerindian and 0.25 Oceanian."

Good point.

Gene diversity at SLC24A5 is highest in Amerindians and lowest in Europeans. East Asians are intermediate. http://anthropogenesis.kinshipstudies.org/2014/10/ancient-ust-ishim-dna-as-seen-from-the-americas/.

So, ANE, light skin, Y-DNA hgs C (Kostenki, la Brana) and Q, EDAR all seem to be products of a population movement originating in the Americas.

Mike Thomas said...

German

How did these ANE rich, HG C peolle get
to North America in the first place ?

German Dziebel said...

@Mike Thomas

The usual way: via the Bering Strait. Only not 12,000 years ago, but much earlier. And then they migrated back to the Old World via the same land bridge. The same happened with woolly mammoths.

postneo said...

@german @mike

Aren't the berring straits more nutrient rich than western siberia during the LGM and onwards.

This could account for greater mutations to have occurred in these regions as compared to central and eastern europe.

Tobus said...

@German:Gene diversity at SLC24A5 is highest in Amerindians

Not before Columbus it isn't - compare the Karitiana, Surui, Pima etc. samples. It's only in Amerindian samples with post-1491 admixture that there's any diversity at this locus. (http://alfred.med.yale.edu/alfred/hetgraph.asp?siteuid=SI007419V&cutoff=0.25)

Alberto said...

@postneo

I'm not proposing a very specific location other than Central Asia, basically because of the lack of data. That area in Turkmenistan seems to show an early and quite developed Neolithic civilization, and it's one of the few sites excavated. But I'm open to better suggestions.

However, the further you go south, the less likely the contact between these ANE populations and EHG becomes. And I always thought that Kazakhstan could be a zone of contact between them (and that's why EHG and Siberian population have high ANE).

What would be your preferred area to place this population?

German Dziebel said...

@Tobus

"Not before Columbus it isn't"

I gave a link to a published source.

Tobus said...

@German:I gave a link to a published source.

That "link to a published source" is simply a link to your own blog!

The ultimate source of the figure you reference in your blog is HGDP which includes Columbians and Mayans in their "America" group - populations with significant recent European admixture.

German Dziebel said...

@Tobus

"That "link to a published source" is simply a link to your own blog!

Of course, I'm going to link it to my blog.

"The ultimate source of the figure you reference in your blog is HGDP which includes Columbians and Mayans in their "America" group - populations with significant recent European admixture."

Bullshit! Show me the data breakdown. BTW, we discussed it elsewhere apropos (http://www.g3journal.org/content/3/11/2059.full) and the paper talked about unadmixed Amerindian haplotypes.

Chad Rohlfsen said...

This one worked for Loschbour. I am going to ask Nick about it.

Samara_HG 12.4
LaBrana1 77.4
BedouinB 10.1


best coefficients: 0.124 0.774 0.101
ssres:
-0.000251376 0.000262097 0.000073354 0.000050382 0.000115783 -0.000113889 0.000164405 -0.000141080
-1.540153729 1.605838849 0.449431381 0.308685189 0.709389903 -0.697784398 1.007293557 -0.864381605

Jackknife mean: 0.130267277 0.760702819 0.109029903
std. errors: 0.087 0.159 0.089

Tobus said...

@German:
Bullshit! Show me the data breakdown.

Calm down. The HGDP populations are publicly available here: http://hgdp.uchicago.edu/Phased_data/H938_Clumps.clst.txt_check.Continent.format.order.NR.gz
I already posted the ALFRED link showing heterozygosity for the SL24A5 rs1426654 alleles in these and other various populations. You can confirm for yourself that unadmixed Native Americans are almost fixed ancestral for this SNP.

we discussed it elsewhere apropos (http://www.g3journal.org/content/3/11/2059.full)

You must be getting me confused with someone else, I've never discussed that paper with you.

and the paper talked about unadmixed Amerindian haplotypes.

On the contrary the paper confirms what I'm saying: eg "we noted a trend toward greater counts in the admixed New World populations". See the frequency lists in Table S1 as well - the non-admixed American pops have little to no variation at this locus. I can't see any mention of "unadmixed Amerindian haplotypes" anywhere in this paper.

Your original point seems to be confusing variation across the entire SLC24A5 gene (some 21,420 base pairs) with increased depigmentation. In fact only one of the SLC24A5 base pairs is associated with depigmentation (ie rs1426654) and it's actually the *loss* of variation across the whole gene that is associated with a depigmented phenotype. See in the original figure how Europeans have the *least* variation? It's selection for a single haplotype (C11 in the above paper) that has caused this lack of variation in Europeans, and it's only that particular haplotype that is associated with depigmentation.

windy said...

"The high frequency of the East Asian-specific EDAR allele among the Motala foragers is even more surprising for me than their inferred light skin. But it does at least gel with the earlier finding that Scandinavian hunter-gatherers did not contribute significant ancestry to modern Europeans"

What about modern North Europeans? Shovel-shaped incisors (controlled by EDAR) are common among Finns, at least. But that could also be due to later Asian influence.

Davidski said...

Northern Scandinavia, Finland and northern Russia experienced more recent Siberian gene flow than the rest of Europe. These migrations might have brought Uralic languages to Northeastern Europe.