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Wednesday, October 22, 2014

Ust-Ishim belongs to K-M526

Not long ago I predicted that Ust-Ishim belonged to a basal clade of Y-chromosome haplogroup P (see here). As it turns out, the 45,000 year-old western Siberian genome belongs to K(xLT) or K-M526, which is actually pretty close to my guess. The paper is behind a paywall here, but the extensive supp info is free. Here's a map to help visualize the information.

The genome was sequenced from the fossil of a femur bone found near the village of Ust-Ishim, on the banks of the Irtysh River. This area is very close to the Urals, and almost in the middle of the former Mammoth steppe that once stretched across North Eurasia from Iberia to Alaska. Interestingly, M526 is an ancestral mutation to the markers that define Y-chromosome haplogroups N, Q and R, which today dominate North Eurasia and the Americas.

In fact, R1a and R1b are the most frequent haplogroups in Europe. It's therefore plausible that most European males derive their paternal ancestry from North Eurasian hunter-gatherers whose ancestors spread out across Eurasia from the Middle East over 45,000 years ago.

I know that a lot of people have been arguing recently that K-M526 and the derived P-M45 originated and diversified in Southeast Asia, and then migrated north well within the last 45,000 years (for instance, see here). However, considering that K-M526 was already in reindeer country 45,000 years ago, as well as the Denisovan (ancient Siberian hominin) admixture among Southeast Asians, that might well turn out to be the equivalent of arguing that up is down and down is up.

By the way, Ust-Ishim also belongs to pan-Eurasian mitochondrial (mtDNA) haplogroup R*, and in terms of genome-wide genetic structure appears roughly intermediate between West and East Eurasians. These outcomes fit very nicely with its Y-haplogroup.

However, it's slightly closer to Mesolithic Iberian La Brana-1, Upper Paleolithic Siberian MA-1 (or Mal'ta boy), and present-day East Asians, than to present-day West Eurasians, including Europeans. That's because it lacks "ancestry from a population that did not participate in the initial dispersals of modern humans into Europe and Asia". This is obviously the so called Basal Eurasian admixture discussed in Lazaridis et al. (see here), which was probably spread across West Eurasia by early Neolithic farmers.

Also worth mentioning is that Ust-Ishim harbors longer stretches of Neanderthal chromosomal segments than present-day Eurasians, which suggests that admixture between modern humans and Neanderthals took place in the Middle East not long before the ancestors of Ust-Ishim moved into Siberia (50-60,000 years ago). But this was already covered months ago, and you'll find lots of links on the topic on Google.


Qiaomei Fu et al., Genome sequence of a 45,000-year-old modern human from western Siberia, Nature 514, 445–449 (23 October 2014) doi:10.1038/nature13810

Tuesday, October 21, 2014

Ancient genomes from the Great Hungarian Plain

This open access paper on the genetic prehistory of the Great Hungarian Plain is full of surprises. Here are a few of my observations:

- Four of the genomes from a Neolithic farming context produced two Y-haplogroups previously identified in Mesolithic European hunter-gatherers (I2a and C6), and one of the samples (KO1) could probably pass for a Mesolithic hunter-gatherer overall, suggesting that males of hunter-gatherer origin played a major role in early European Neolithic societies. But what's happened to the C6 since then?

- The two Bronze Age genomes, BR1 and BR2, look very present-day French, and probably western French at that, in both the Principal Component and Admixture analyses. Indeed, they clearly show a northern influence relative to all of the Neolithic farmers and the Iron Age IR1. And yet, BR2 belongs to Y-haplogroup J2a1, which is generally seen as a Near Eastern marker.

- IR1 is described as a pre-Scythian genome with both East Eurasian and North Caucasian affinities (it's not clear in the paper whether it belongs to Y-haplogroup N and mtDNA G2a1, or vice versa, although either way works in this context). However, it also shows significant Northern European-like ancestry, and is even inferred to have fair hair, which makes me think that its eastern shift might be in large part due to Eastern Hunter-Gatherer (EHG) or Yamnaya-related admixture, which is now pervasive across Northern Europe (see here).

- Many people, including myself nowadays, see the Carpathian Basin as potentially a major staging point for the expansion of Y-chromosome haplogroup R1b into Central and Western Europe during the Bronze Age. And yet, it's again missing from the line-up.

- The T allele at SNP rs4988235, associated with lactase persistence into adulthood in Europeans, is only present among the two most recent genomes: BR2 and IR1. This suggests that selection for this allele, which now reaches frequencies of well over 50% in much of Europe, post dates not only the Neolithic but also the early Indo-European period, and was possibly most intense during the metal ages.

- Some of the Neolithic samples are clearly shifted towards the Bedouins (Bed) in Figure 2, relative to Oetzi the Iceman, a Copper Age genome from the Tyrolean Alps, which is generally considered to be typical of European Neolithic farmers (see below). So perhaps further sampling of Neolithic remains from southern Europe, in particular the southern Balkans, might reveal early farmers who actually cluster with Near Eastern populations, rather than Europeans?

- The authors found a sweetspot for extracting ancient DNA from humans: "the petrous portion of the temporal bone, the densest bone in the mammalian body". The amount of endogenous DNA salvaged from this part of the skull exceeds those from other bones by up to 183-fold. This is obviously great news, and probably means we can expect many more ancient genomes to be published in the near future.


Gamba, C. et al. Genome flux and stasis in a five millennium transect of European prehistory. Nat. Commun. 5:5257 doi:10.1038/ncomms6257 (2014).

See also...

First I1-M253 from prehistoric Europe

Monday, October 20, 2014

PIE homeland update: paleogenomics supports the steppe hypothesis

Several people tweeted from Iosif Lazaridis' talk at the ASHG earlier today, which focused on ancient DNA from 65 Neolithic and Bronze Age Europeans. Here are a couple of the tweets that caught my eye:
There was an influx from north Eurasian steppe into Europe after advent of farming. Consistent w linguistic evidence.Link

Admixture shows multiway admixture among late Neolithic ancient samples. Yamnaya good source as 3rd ancestral reference.Link

So it seems that latest paleogenomics data support the linguists and archeologists who see the Proto-Indo-European (PIE) homeland on the Eastern European steppe. For some background on that, check out the videos here.

Razib also tweeted a few times from the talk, and as far as I can tell, his main point was that the Yamnaya samples showed affinity to the Ancient North Eurasian (ANE) proxy Mal'ta boy, but were also partly of Near Eastern origin, and indeed could be modeled as a 50/50 mixture between present-day Armenians and ancient Karelian hunter-gatherers. He also said that the ancient Karelians were classified as eastern hunter-gatherers (let's call them EHG for now), along with the hunter-gatherers from the Samara Valley, which probably means they carried a lot of ANE admixture.

Moreover, he added that Corded Ware genomes from late Neolithic Germany were estimated at 75% Yamnaya, while another source from the talk revealed to me that they carried a surprisingly "large chunk" of EHG, estimated at a minimum of 36%.

All of this makes sense, considering that during the Neolithic much of present-day Ukraine west of the Dnieper was home to the Cucuteni-Trypillian farmers, probably of Near Eastern origin, while at the same time large groups of indigenous hunter-gatherers still foraged east of the Dnieper. Based on archeological data, it seems these two groups mixed at some point, becoming mobile pastoralists associated with the Yamnaya culture, and then expanded in all directions during the late Neolithic/early Bronze Age, potentially spreading Indo-European culture and languages as they went.

The Cucuteni-Trypillian farmers might well have been very similar to present-day Armenians, although probably without the 10-15% of ANE carried by them, which likely arrived in eastern Anatolia with the early Indo-Europeans from the steppe.

By the way, it's possible that the Karelian hunter-gatherers are the same samples as those featured in Der Sarkissian et al. 2013., where they were reported to carry mitochondrial (mtDNA) haplogroups C1 (3 instances), U2e (x2), U4 (x2), U5a and H.

Here's a spatial map from that study showing genetic distances between the ancient Karelian mtDNA and that of modern populations.

Der Sarkissian C, Balanovsky O, Brandt G, Khartanovich V, Buzhilova A, et al. (2013) Ancient DNA Reveals Prehistoric Gene-Flow from Siberia in the Complex Human Population History of North East Europe. PLoS Genet 9(2): e1003296. doi:10.1371/journal.pgen.1003296

See also...

Corded Ware Culture linked to the spread of ANE across Europe

Guessing game

Coming soon: genome-wide data from more than forty 3-9K year-old humans from the ancient Russian steppe

Analysis of Hinxton4 - ERS389798

Hinxton4, or ERS389798, is one of five ancient English genomes stored at the Sequence Read Archive under accession number ERP003900. However, this analysis is based on the latest genotype file of Hinxton4 available at Genetic Genealogy Tools. For more information and some speculation about these genomes see my earlier blog post here.

I still don't know who these samples represent exactly, but in all likelihood, this is one of the two Iron Age sequences from this collection, and probably belongs to a Briton of Celtic stock. Note, for instance, its high affinity to the present-day Irish, relatively low North Sea score in the Eurogenes K15, and pronounced western shift on the second Principal Component Analysis (PCA) plot below.

Interestingly, Lithuanians top its shared drift list based on the Human Origins dataset and more than 360K SNPs. I'm not entirely sure what this means, but it's probably related in some way to the unusually high level (>45%) of indigenous European hunter-gatherer ancestry carried by Lithuanians.

Shared drift stats in the form f3(Mbuti;Hinxton4,Test) - Eurogenes dataset

Shared drift stats in the form f3(Mbuti;Hinxton4,Test) - Human Origins dataset

Eurogenes K15 4 Ancestors Oracle results

See also...

Analysis of Hinxton2 - ERS389796

Analysis of Hinxton3 - ERS389797

Friday, October 17, 2014

Analysis of Hinxton3 - ERS389797

Hinxton3, or ERS389797, is one of five ancient English genomes stored at the Sequence Read Archive under accession number ERP003900. However, this analysis is based on the latest genotype file of Hinxton3 available at Genetic Genealogy Tools. For more information and some speculation about these genomes see my earlier blog post here.

Despite the exaggerated North Sea score in the Eurogenes K15, Hinxton3 could easily pass for a present-day Briton from the eastern coast of England or Scotland, albeit with a stronger than usual pull towards Scandinavia. Indeed, the f3-statistics show that it shares most genetic drift with the British and Icelanders from Eurogenes and Human Origins, respectively.

Shared drift stats in the form f3(Mbuti;Hinxton3,Test) - Eurogenes dataset

Shared drift stats in the form f3(Mbuti;Hinxton3,Test) - Human Origins dataset

Eurogenes K15 4 Ancestors Oracle results

See also...

Analysis of Hinxton2 - ERS389796

Analysis of Hinxton4 - ERS389798

Analysis of Hinxton2 - ERS389796

Hinxton2, or ERS389796, is one of five ancient English genomes stored at the Sequence Read Archive under accession number ERP003900. However, this analysis is based on the latest genotype file of Hinxton2 available at Genetic Genealogy Tools. For more information and some speculation about these genomes see my earlier blog post here.

Interestingly, f3-statistics in the form f3(Mbuti;Hinxton2,Test) show that Hinxton2 shares most genetic drift with present-day Danes and Norwegians. Please refer to the relevant spreadsheets below.

Shared drift stats in the form f3(Mbuti;Hinxton2,Test) - Eurogenes dataset

Shared drift stats in the form f3(Mbuti;Hinxton2,Test) - Human Origins dataset

Eurogenes K15 4 Ancestors Oracle results

See also...

Analysis of Hinxton3 - ERS389797

Analysis of Hinxton4 - ERS389798

Sunday, October 12, 2014

Ancient genomes and the calculator effect

Several ancient genomes have been posted online as text files and uploaded to GEDmatch over the last couple of weeks, and many more are likely to follow in the future. A lot of people have already taken this opportunity to analyze these files with various online ancestry tools, usually DIY calculators.

That's actually not a bad way of doing things, as long as everyone's aware that almost all of these calculators produce biased results. They produce biased results because they violate a very basic rule of science, which is this:
Do not test more than one variable at a time.
Obviously, the variable we want to test with these calculators is ancestry. However, when the reference samples are tested in a different way to the test samples, which is what usually happens, then this adds another variable to the proceedings. As a result, we simply can't compare the results of the reference samples to those of the test samples.

I know that a lot of people find this difficult to grasp, and many just seem hell bent on not grasping it. However, anyone who isn't completely insane, and takes five minutes out of their day to try and understand the concepts involved, has to agree that this is a real problem. It can be proven empirically, like I did over two years ago (see here).

I suspect that a lot of confusion has been caused by the fact that the people who were used as reference samples in the making of the various DIY calculators saw highly accurate results when running them, and so assumed everything was fine. The accuracy of the DIY calculators for such people is indeed impressive, and I show that at the link above, but unfortunately the story is very different for everyone else.

Here's the good news: the Eurogenes calculators don't suffer from the calculator effect. That's because the reference samples are treated in the same way as the test samples, so there's only one variable: ancestry. What this means is that when you run a modern or ancient genome with a Eurogenes calculator you can confidently compare the result to those of the reference samples (provided enough SNPs are used), and then be able to make sensible inferences about its genetic origins.