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Thursday, November 21, 2013

First genome of an Upper Paleolithic human

A new paper at Nature reports on the genome of a 24,000 year-old Siberian known as Mal'ta boy or MA-1. Here's the abstract:

The origins of the First Americans remain contentious. Although Native Americans seem to be genetically most closely related to east Asians1, 2, 3, there is no consensus with regard to which specific Old World populations they are closest to 4, 5, 6, 7, 8. Here we sequence the draft genome of an approximately 24,000-year-old individual (MA-1), from Mal’ta in south-central Siberia9, to an average depth of 1×. To our knowledge this is the oldest anatomically modern human genome reported to date. The MA-1 mitochondrial genome belongs to haplogroup U, which has also been found at high frequency among Upper Palaeolithic and Mesolithic European hunter-gatherers10, 11, 12, and the Y chromosome of MA-1 is basal to modern-day western Eurasians and near the root of most Native American lineages5. Similarly, we find autosomal evidence that MA-1 is basal to modern-day western Eurasians and genetically closely related to modern-day Native Americans, with no close affinity to east Asians. This suggests that populations related to contemporary western Eurasians had a more north-easterly distribution 24,000 years ago than commonly thought. Furthermore, we estimate that 14 to 38% of Native American ancestry may originate through gene flow from this ancient population. This is likely to have occurred after the divergence of Native American ancestors from east Asian ancestors, but before the diversification of Native American populations in the New World. Gene flow from the MA-1 lineage into Native American ancestors could explain why several crania from the First Americans have been reported as bearing morphological characteristics that do not resemble those of east Asians2, 13. Sequencing of another south-central Siberian, Afontova Gora-2 dating to approximately 17,000 years ago14, revealed similar autosomal genetic signatures as MA-1, suggesting that the region was continuously occupied by humans throughout the Last Glacial Maximum. Our findings reveal that western Eurasian genetic signatures in modern-day Native Americans derive not only from post-Columbian admixture, as commonly thought, but also from a mixed ancestry of the First Americans.

Indeed, MA-1 looks like he could be an early ancestor of present-day West Eurasians, including and especially Europeans. Mitochondrial haplogroup U was almost fixed in Upper Paleolithic and Mesolithic Europe, while R1a and R1b are, after all, the most common and widespread Y-chromosome haplogroups in Europe today.

Below is the bar graph from the K=9 ADMIXTURE analysis, which turned out to be the optimal run. Note that the Mal'ta sample appears mostly South Asian (37%), European (34%), and Amerindian (26%), but also with minor Oceanian ancestry (4%). Interestingly, among the Europeans, it's the groups from Northern and Eastern Europe that carry the highest levels of these components. This is probably a reflection, at least in large part, of their elevated indigenous European hunter-gatherer ancestry.

At K = 9, MA-1 is composed of five genetic components of which the two major ones make up ca. 70% of the total. The most prominent component is shown in green and is otherwise prevalent in South Asia but does also appear in the Caucasus, Near East or even Europe. The other major genetic component (dark blue) in MA-1 is the one dominant in contemporary European populations, especially among northern and northeastern Europeans. The co-presence of the European-blue and South Asian green in MA-1 can be interpreted as admixture of the two in MA-1 or, alternatively, MA-1 could represent a proto-western Eurasian prior to the split of Europeans and South Asians. This analysis cannot differentiate between these two scenarios. Most of the remaining nearly one third of the MA-1 genome is comprised of the two genetic components that make up the Native American gene pool (orange and light pink). Importantly, MA-1 completely lacks the genetic components prevalent in extant East Asians and Siberians (shown in dark and light yellow, respectively). Based on this result, it is likely that the current Siberian genetic landscape, dominated by the genetic components depicted in light and dark yellow (Figure SI 6), was formed by secondary wave(s) of immigrants from East Asia.

Here's a figure showing the levels of shared genetic drift between MA-1 and 147 present-day non-African populations. Among the Europeans it's the Lithuanians, Northwestern Russians and Baltic and Volga Finns who are most similar to the ancient sample. It's also interesting to note the relatively high position on the list of the Kalash from South Central Asia and Lezgins from the North Caucasus. At the bottom are Bedouins and Palestinians, mainly because of their non-trivial Sub-Saharan admixture, followed by Oceanians, East Asians, and South Indians, probably due to deep differentiation between their main ancestral clades and that of MA-1.

I've heard that the same team of scientists is now trying to sequence genomes from Upper Paleolithic sites west of Mal'ta. I wonder how far west? I see that the authors mention the Sungir site from near Moscow a couple of times in the paper, in relation to its similarity to the Mal'ta site. Perhaps they're working on a Sungir genome right now? If so, what's the bet that the Y-DNA turns out to be another basal R?


Raghavan et al., Upper Palaeolithic Siberian genome reveals dual ancestry of Native Americans, Nature, (2013), Published online 20 November 2013, doi:10.1038/nature12736

Saturday, November 16, 2013

mtDNA haplogroup U5a link between Eastern Europe and Iran

I'm reading a new paper at PLoS ONE on the mitochondrial DNA of Iranians. It's the first study to tackle the topic of Iranian maternal ancestry using complete mtDNA sequences. Here are a couple of quotes that caught my eye:

Between the third and second millennia BCE the Iranian Plateau became exposed to incursions of pastoral nomads from the Central Asian steppes, who brought the Indo-Iranian language of the Indo-European family, which eventually replaced Dravidian languages, perhaps by an elite-dominance model [13,17,20].


The U5a1a’g cluster itself (based on HVS1 sequence data) is concentrated in populations of the Pontic-Caspian steppe, extending from Romania, Ukraine, southern Russia and northwestern Kazakhstan to the Ural Mountains. The highest frequencies of the U5a1a’g were reported in the Volga-Ural region (5.3%), in particular in Bashkirs (4.3%) and Tatars (3.9%) [75], although the frequency varies from ,2.7% in Russians to ,1.5% in populations of the northern Caucasus [64,76–81]. It is worth mentioning that despite the low frequency of U5a1a’g haplotypes in Central Asian populations of Turkmens, Karakalpaks, Kazakhs and Uzbeks (,1.5% according to the data of [82], some haplotypes were common between Karakalpaks (haplotype marked by mutation at np 16293), Turkmens (by mutation at np 64) and Iranians. So, it seems likely that the sub-cluster U5a1g or its founder has arrived to Iran from Eastern Europe/southern Ural via the Caspian Sea coastal route.

Derenko M, Malyarchuk B, Bahmanimehr A, Denisova G, Perkova M, et al. (2013) Complete Mitochondrial DNA Diversity in Iranians. PLoS ONE 8(11): e80673. doi:10.1371/journal.pone.0080673

Thursday, November 14, 2013

The story of R1b: it's complicated

Ancient DNA is painting a remarkable picture of the period of European prehistory known as the Late Neolithic/Early Bronze Age. It's showing that after the collapse of genetically Near Eastern-like farming populations of middle Neolithic Central Europe - probably as a result of climate fluctuations, disease, famine and increasing violence - the vacuum was filled by genetically much more European-like groups from the eastern and western peripheries of Neolithic Europe.

First came the settlers from the east, belonging to the vast archeological horizon known as the Corded Ware Culture (CWC). About three hundred years later they were joined in Central Europe by migrants from the Atlantic Fringe, belonging to the Bell Beaker Culture (BBC). During the early Bronze Age, the CWC disappeared, and was replaced by the Unetice Culture (UC), which briefly overlapped with the late BBC.

Ancient DNA recovered to date suggests that the Bell Beakers were genetically the archetypal Western Europeans, characterized by Western European-specific mtDNA H subclades and Y-chromosome haplogroup R1b. Interestingly, R1b has also been found among remains of aboriginals from the Canary Islands, just off the coast of northwest Africa. It might be a stretch to attribute this directly to the Bell Beakers, but they were certainly capable sailors, so perhaps not?

On the other hand, the CWC and UC populations appear to have been Eastern Europeans to the core, carrying relatively low levels of mtDNA H, and showing strong mtDNA affinity to Bronze Age Kurgan groups of Kazakhstan and South Siberia.

Here are a couple of figures from recent studies, Brandt et al. and Brotherton et al., respectively, illustrating much of what I just said.

So it seems everything is falling into place, with ancient DNA, archeology, and modern European genetic substructures all showing basically the same phenomenon.

However, for a while now the ever more precise present-day phylogeography of R1b has been hinting that this haplogroup might not have expanded across Europe from the west. That's because the most basal clades of R1b are found in West Asia, and its SNP diversity decreases sharply from east to west in Europe. Below is a schematic of the latest phylogeography of R1b. It was presented at the recently held 9th Annual International Conference on Genetic Genealogy by Arizona University population geneticist Dr. Michael Hammer.

And here is another map shown by Hammer at the same conference, illustrating the frequencies of various R1b subclades across Europe.

I didn't see the presentation, so I don't know what Hammer actually said. But it appears as if his theory is that R1b spread across Europe from the Balkans during the late Neolithic or later, and then exploded in-situ from certain areas of Central and Western Europe during the metal ages. If true, this scenario obviously doesn't match the presumed west to east expansion of the Bell Beakers.

But here's yet another slide from Hammer's talk, which shows the frequency peaks of the most common European subclades of R1b: U106, L21 and U152. Curiously, these peaks are all located in and around former Bell Beaker territory (second image below, from Wikipedia).

Admittedly, we only have two Y-chromosome results from Bell Beaker remains, both from the same site in Germany dated to around 4500 YBP, but both belonging to R1b. Based on that, plus all of the indirect evidence outlined above, it's already very difficult to shake the association between Bell Beakers and R1b. So I'm thinking there are three possible explanations why the latest R1b phylogeography doesn't support a Bell Beaker-driven expansion of this haplogroup in Europe.

1) The current mainstream theory positing the origin of the Bell Beaker Culture in Portugal is wrong, and the earliest Bell Beakers expanded from East Central Europe, as was once thought.

2) The latest R1b phylogeography is based on limited sampling, and many more individuals need to be tested from former Bell Beaker areas in Iberia and France to catch the basal R1b subclades in these regions.

3) The people who were to become the Bell Beakers in Iberia originally came from the southern Balkans, via maritime routes across the Mediterranean, and then dominated Western and Central Europe via a series of migrations and back migrations. The latest R1b phylogeography is simply not intricate enough to properly describe this complicated process.

The first option basically ignores ancient mtDNA data which shows that the Bell Beakers of Central Europe were of Iberian origin, at least in terms of maternal ancestry. So for now, I'm going with the third option, and looking forward to more ancient DNA results.

A lot can be said about what might have pushed the Balkan proto-Bell Beakers to Western Europe during the late Neolithic, if they actually existed. At the time Bulgaria was being invaded by steppe nomads from just north of the Black Sea, and its agricultural communities were disappearing rapidly. I suppose the ancestors of the Bell Beakers might have been refugees trying to escape these nomads. Then again, perhaps they were the descendants of the nomads who learned to sail after reaching the Mediterranean? I might revisit the issue when I have more data to work with.


Michael Hammer, Origins of R-M269 Diversity in Europe, University of Arizona, FamilyTreeDNA, 9th Annual Conference

Guido Brandt, Wolfgang Haak et al., Ancient DNA Reveals Key Stages in the Formation of Central European Mitochondrial Genetic Diversity, Science 11 October 2013: Vol. 342 no. 6155 pp. 257-261 DOI: 10.1126/science.1241844

Brotherton et al., Neolithic mitochondrial haplogroup H genomes and the genetic origins of Europeans, Nature Communications 4, Article number: 1764, Published 23 April 2013, doi:10.1038/ncomms2656