Ancient DNA has revolutionized our understanding of human population history. However, its potential to examine how rapid cultural evolution to new lifestyles may have driven biological adaptation has not been met, largely due to limited sample sizes. We assembled genome-wide data from 1,291 individuals from Europe over 10,000 years, providing a dataset that is large enough to resolve the timing of selection into the Neolithic, Bronze Age, and Historical periods. We identified 25 genetic loci with rapid changes in frequency during these periods, a majority of which were previously undetected. Signals specific to the Neolithic transition are associated with body weight, diet, and lipid metabolism-related phenotypes. They also include immune phenotypes, most notably a locus that confers immunity to Salmonella infection at a time when ancient Salmonella genomes have been shown to adapt to human hosts, thus providing a possible example of human-pathogen co-evolution. In the Bronze Age, selection signals are enriched near genes involved in pigmentation and immune-related traits, including at a key human protein interactor of SARS-CoV-2. Only in the Historical period do the selection candidates we detect largely mirror previously-reported signals, highlighting how the statistical power of previous studies was limited to the last few millennia. The Historical period also has multiple signals associated with vitamin D binding, providing evidence that lactase persistence may have been part of an oligogenic adaptation for efficient calcium uptake and challenging the theory that its adaptive value lies only in facilitating caloric supplementation during times of scarcity. Finally, we detect selection on complex traits in all three periods, including selection favoring variants that reduce body weight in the Neolithic. In the Historical period, we detect selection favoring variants that increase risk for cardiovascular disease plausibly reflecting selection for a more active inflammatory response that would have been adaptive in the face of increased infectious disease exposure. Our results provide an evolutionary rationale for the high prevalence of these deadly diseases in modern societies today and highlight the unique power of ancient DNA in elucidating biological change that accompanied the profound cultural transformations of recent human history.

Sometimes statistics confirm what you can already intuitively discern. I’m an avid reader of the ancient DNA and pigmentation literature. It was immediately obvious to me that the Bronze Age Northern European samples were darker than modern populations in that region. There are massive sample sizes for modern Europeans, and it jumped out at me that the derived SNP at SLC45A2 was at a lower frequency two to four thousand years ago than it is today. This paper confirms that selection not only occurred during the Bronze Age, but has been happening in the historical period…

Note: The backstory on why I had my suspicions about this goes back to 2009. When the first Reich lab India paper came out I was pretty skeptical that the “Ancestral North Indians” were so similar to Northern Europeans. My rationale was straightforward: we should see way more blonde and blue-eyed people in Northern India and Pakistan. Nick Patterson pointed out the relevance of natural selection. Perhaps the Northern Indians got darker? There is a bit of evidence of this for some loci, but the Narasimhan et al. paper had a bunch of Sintashta, who are probably the best ancestral population proxy for the early Indo-Aryans, and they were clearly just not as lightly pigmented as related people on the Baltic today. The Sintashta were very similar to their relatives in Poland genetically, but they diverged from their Northern European relatives 4,500 years ago as the Fatyanovo population migrated eastward, and were probably in India when selection was changing the allele frequencies around SLC45A2.

Magna Graecia lives!

Posted on June 23, 2022June 23, 2022 by Razib Khan

Assessing temporal and geographic contacts across the Adriatic Sea through the analysis of genome-wide data from Southern Italy:

Southern Italy was characterised by a complex prehistory that started with different Palaeolithic cultures, later followed by the Neolithization and the demic dispersal from the Pontic-Caspian Steppe during the Bronze Age. Archaeological and historical evidences point to a link between Southern Italians and the Balkans still present in modern times. To shed light on these dynamics, we analysed around 700 South Mediterranean genomes combined with informative ancient DNAs. Our findings revealed high affinities of South-Eastern Italians with modern Eastern Peloponnesians, and a closer affinity of ancient Greek genomes with those from specific regions of South Italy than modern Greek genomes. The higher similarity could be associated with a Bronze Age component ultimately originating from the Caucasus with high Iranian and Anatolian Neolithic ancestries. Furthermore, extremely differentiated allele frequencies among Northern and Southern Italy revealed putatively adapted SNPs in genes involved in alcohol metabolism, nevi features and immunological traits.

This paper finally seems to straightout admit that the statistics for using Greeks as a donor population can be messed up by Slavic migration. There’s heterogeneity though. For example, Maniotes are good donors to eastern Sicily. Maniotes are famous for having been pagan until the 800’s, because their godforsaken peninsula was so isolated from the rest of the world. And, in these data they seem to have less Slavic ancestry, which is what you’d expect if they were so isolated.

The modern human family tree might be shallower that I’ve been saying

Posted on June 18, 2022June 18, 2022 by Razib Khan

Estimating population split times and migration rates from historical effective population sizes:

The estimation of effective population sizes (Ne) through time is of fundamental interest in population genetics, but the interpretation of Ne as the effective number of breeding individuals in the population is challenged by the effect of population structure. In fact, variation in Ne reported in many studies may be a consequence of changes in migration rates between populations rather than changes in actual population size. We address this long-standing problem here by constructing joint models of population size changes, migration, and divergence that can adjust temporal estimates of Ne and estimate the actual Ne of a local deme connected to another population through migration. We also develop a method for estimating divergence times and migration rates taking into account complex scenarios of changing population sizes. We apply the method to previously published data from humans, and show that, when taking migration and changes in Ne into account, the estimated divergence between the San and Dinka populations is approximately 108 kya, and not 255 kya as reported in a previous study. Using simulations, we demonstrate that the previously reported and surprisingly old estimates of divergence between San and Dinka is in fact caused by a quantifiable estimation bias due to changes in Ne through time.

If you read this blog you know I’ve alluded to really deep structure in Africa for a while. Some work using ancient Khoisan samples from South Africa puts the divergence between this population and other moderns as far back as 300,000 years ago. Privately a lot of geneticists were skeptical of this, but the published record is what it is. But there were many simplifying assumptions in these models. You can see this in N_e calculations on admixed (recently) populations as if they weren’t admixed but ancient groups. If you have an admixed population with higher genetic diversity you’re going to estimate a larger effective population…but really it’s just the pooled population of two distinct ancestral populations (or more than two, depending).

This preprint, along with A weakly structured stem for human origins in Africa, is pushing the divergence times within Africa closer to 100-125,000 years ago, as opposed to 200,000 years ago. They do make an estimate for Eurasians that seems to be corroborated by archaeology and ancient DNA:

For Han-French divergence, the model with the highest composite likelihood was one with a split time of 1505 generations (i.e. 43,645 years ago assuming 29 years per generation) and a mostly unidirectional migration rate of 2.92 from Han to French (Table 1). We also replicate the results from Sj¨odin et al. [2021], in which the TT method infers nonsensical negative split times between Han and French. The unidirectional migration inferred from Han to French is in line with current models of the peopling of Europe through waves of farmers coming from central Eurasia [Haak et al., 2015].

The 43,645 years ago estimate seems broadly correct. Ancient DNA and archaeology I think point to a period definitely before 40,000 years ago, but admixture with Neanderthals and the spread of modern human technologies means it is unlikely to be very much before 50,000 years ago (i.e., not 60,000 years ago). The “Han” to “French” migration is strange, but there is suggestive evidence deep in supplements of East Asian migration into late Pleistocene/early Holocene Europe into Mesolithic foragers. This might be common Ancestral North Eurasian ancestry, or something different. I’m not sure that this model totally checks out and we know what’s going on. Probably one reason it remains in the supplements of these papers.

They’re getting estimates between Sardinians and Africans a bit before 100,000 years ago…though they admit that it’s probably inflated by archaic (Neanderthal admixture). That value seems about right and indicates a long period of incubation of the ancestrally non-African populations within the context of African/perhaps West Asian population structure.

For more complexity/detail, see The genomic origins of the world’s first farmers, which purports to better model N_e variations to get better divergence times within Europe between various forager and farmer lineages. This group has not used “Basal Eurasians” in their human genetics papers the last few times. They don’t believe it’s needed.

Is ancient DNA a biased view?

Posted on May 30, 2022May 30, 2022 by Razib Khan

Over at my Substack Iberia: Ancient Europe’s Edge of the Earth (part 1) – Unpacking prehistoric Spanish and Portuguese genetics elicited a comment from Walter Bodmer questioning the representative of ancient burials (i.e., were they just elites?).

My response:

– I bet forager societies were in HWE. That is, there’s no major stratification due to class since class differences are minimal/attenuated.

– A single genome has been pretty predictive of future and past diversity for a given population (e.g., WHG).

– There are populations, like India’s, that are highly stratified by class for many centuries (thousands of years?). But this is the exception, not the rule.

Cities are where people go to flourish, and then die

Posted on May 19, 2022May 19, 2022 by Razib Khan

Stable population structure in Europe since the Iron Age, despite high mobility:

Ancient DNA research in the past decade has revealed that European population structure changed dramatically in the prehistoric period (14,000-3,000 years before present, YBP), reflecting the widespread introduction of Neolithic farmer and Bronze Age Steppe ancestries. However, little is known about how population structure changed in the historical period onward (3,000 YBP – present). To address this, we collected whole genomes from 204 individuals from Europe and the Mediterranean, many of which are the first historical period genomes from their region (e.g. Armenia, France). We found that most regions show remarkable inter-individual heterogeneity. Around 8% of historical individuals carry ancestry uncommon in the region where they were sampled, some indicating cross-Mediterranean contacts. Despite this high level of mobility, overall population structure across western Eurasia is relatively stable through the historical period up to the present, mirroring the geographic map. We show that, under standard population genetics models with local panmixia, the observed level of dispersal would lead to a collapse of population structure. Persistent population structure thus suggests a lower effective migration rate than indicated by the observed dispersal. We hypothesize that this phenomenon can be explained by extensive transient dispersal arising from drastically improved transportation networks and the Roman Empire’s mobilization of people for trade, labor, and military. This work highlights the utility of ancient DNA in elucidating finer scale human population dynamics in recent history.

This is the most important: ‘According to a longstanding historical hypothesis, the Urban Graveyard Effect, the influx of migrants in city-centers disproportionately contributed to death rate over birth rate; a process which would contribute to observing individuals as “transient” migrants…’

To me, it confirms that the urban demographics of the ancient world were always transient because of low total fertility.

Ashkenazi Jewish ethnogenesis in light of the Erfurt medieval DNA

Posted on May 18, 2022May 26, 2022 by Razib Khan

Genome-wide data from medieval German Jews show that the Ashkenazi founder event pre-dated the 14th century:

We report genome-wide data for 33 Ashkenazi Jews (AJ), dated to the 14th century, following a salvage excavation at the medieval Jewish cemetery of Erfurt, Germany. The Erfurt individuals are genetically similar to modern AJ and have substantial Southern European ancestry, but they show more variability in Eastern European-related ancestry than modern AJ. A third of the Erfurt individuals carried the same nearly-AJ-specific mitochondrial haplogroup and eight carried pathogenic variants known to affect AJ today. These observations, together with high levels of runs of homozygosity, suggest that the Erfurt community had already experienced the major reduction in size that affected modern AJ. However, the Erfurt bottleneck was more severe, implying substructure in medieval AJ. Together, our results suggest that the AJ founder event and the acquisition of the main sources of ancestry pre-dated the 14th century and highlight late medieval genetic heterogeneity no longer present in modern AJ.

I’ve been asked how this modifies the narrative in my Substack piece. I’d say only on the margins.

The Erfurt community dates to the 1300’s. Interestingly it shows variation in Eastern European ancestry. The authors suggest that genetically there are actually two clusters here, though sociocultural they’re identical. The best guess is that the Eastern European enriched population migrated to Erfurt from the east (there is some difference in the isotope analysis for the teeth). Modern Ashkenazi Jews show less variability and are positioned between the two Erfurt communities in PCA and admixture space. The group without Eastern European ancestry seems to resemble Sephardi and Italian Jews. This isn’t surprising, since they confirm Ashkenazi Jews are some proportional mix of a Middle Eastern population, Italians, and Eastern Europeans, while Sephardi and Italian Jews clearly just lack the last.

The Erfurt community experienced a strong bottleneck, stronger than the one in modern Ashkenazi Jews. This implies that there are other groups out there unsampled, and modern Ashkenazim descend from that. This isn’t surprising, one feedback I got is that there are so many medieval Jews for the inferred population size during this period (going by the texts). I think one issue might be a lot of the medieval Jewish communities simply went extinct. Many of them were undergoing similar dynamics, but not all contributed to future Ashkenazi ancestry.

The homogeneity (relative) of modern Ashkenazim is probably due to late-medieval metapopulation dynamics.

The genetic history of the Serbs (and proto-Serbs)

Posted on August 31, 2021 by Razib Khan

Cosmopolitanism at the Roman Danubian Frontier, Slavic Migrations, and the Genomic Formation of Modern Balkan Peoples:

The Roman Empire expanded through the Mediterranean shores and brought human mobility and cosmopolitanism across this inland sea to an unprecedented scale. However, if this was also common at the Empire frontiers remains undetermined. The Balkans and Danube River were of strategic importance for the Romans acting as an East-West connection and as a defense line against “barbarian” tribes. We generated genome-wide data from 70 ancient individuals from present-day Serbia dated to the first millennium CE; including Viminacium, capital of Moesia Superior province. Our analyses reveal large scale-movements from Anatolia during Imperial rule, similar to the pattern observed in Rome, and cases of individual mobility from as far as East Africa. Between ca 250-500 CE, we detect gene-flow from Central/Northern Europe harboring admixtures of Iron Age steppe groups. Tenth-century CE individuals harbored North-Eastern European-related ancestry likely associated to Slavic-speakers, which contributed >20% of the ancestry of today’s Balkan people.

The humans of Wallacea

Posted on August 26, 2021August 26, 2021 by Razib Khan

A new open-access paper, Genome of a middle Holocene hunter-gatherer from Wallacea:

Much remains unknown about the population history of early modern humans in southeast Asia, where the archaeological record is sparse and the tropical climate is inimical to the preservation of ancient human DNA. So far, only two low-coverage pre-Neolithic human genomes have been sequenced from this region. Both are from mainland Hòabìnhian hunter-gatherer sites: Pha Faen in Laos, dated to 7939–7751 calibrated years before present (yr cal BP; present taken as AD 1950), and Gua Cha in Malaysia (4.4–4.2 kyr cal BP). Here we report, to our knowledge, the first ancient human genome from Wallacea, the oceanic island zone between the Sunda Shelf (comprising mainland southeast Asia and the continental islands of western Indonesia) and Pleistocene Sahul (Australia–New Guinea). We extracted DNA from the petrous bone of a young female hunter-gatherer buried 7.3–7.2 kyr cal BP at the limestone cave of Leang Panninge in South Sulawesi, Indonesia. Genetic analyses show that this pre-Neolithic forager, who is associated with the ‘Toalean’ technocomplex shares most genetic drift and morphological similarities with present-day Papuan and Indigenous Australian groups, yet represents a previously unknown divergent human lineage that branched off around the time of the split between these populations approximately 37,000 years ago. We also describe Denisovan and deep Asian-related ancestries in the Leang Panninge genome, and infer their large-scale displacement from the region today.

The best model seems to be the one to the right: the new Wallacean hunter-gatherer has some ancestry deeply related to Australo-Melanesians, and, another proportion of its ancestry is deeply related to East Asians. In particular, the East Asian-related ancestry seems to be basal or deeply diverged from the paleo-Southern East Asian ancestry. There’s a lot in the structure of ancient East Asian populations that I think we’re pretty unclear about, and need more DNA to really understand what’s going on.

But, I do want to mention that in about 24 hours I’ll be posting a discussion I had with Max Larena about the Denisovan admixture in the Phillippines on my Substack. It’ll be ungated in a few weeks.

Max, and this paper, convince me that Peter Bellwood’s simple model of the spread of farming into Southeast Asia ~4,000 years ago is probably wrong on some level. Too bad, it was a nice simple story. Basically, Northeast Asian populations may have had a presence further south far earlier, and they may have been hunter-gatherers initially.

Turks: Greek or Armenian?

Posted on August 24, 2021August 25, 2021 by Razib Khan

A new paper on Turkey, The genetic structure of the Turkish population reveals high levels of variation and admixture:

We delineated the fine-scale genetic structure of the Turkish population by using sequencing data of 3,362 unrelated Turkish individuals from different geographical origins and demonstrated the position of Turkey in terms of human migration and genetic drift. The results show that the genetic structure of present-day Anatolia was shaped by historical and modern-day migrations, high levels of admixture, and inbreeding. We observed that modern-day Turkey has close genetic relationships with the neighboring Balkan and Caucasus populations. We generated a Turkish Variome which defines the extent of variation observed in Turkey, listed homozygous loss-of-function variants and clinically relevant variants in the cohort, and generated an imputation panel for future genome-wide association studies.

First, I’m surprised how inbred the Turks are in this paper. They need to get more secular quickly and stop marrying their cousins. Second, there’s the classic issue of assuming East Asian ancestry = Turkic ancestry. The reality is that by the time the Turkic tribes arrived in Anatolia they’d already mixed with Iranian peoples in Central Asia, so they may have been 50% non-East Asian by that time. Here’s the relevant section: “Paternal gene flow based on Y chromosome haplogroups C-RPS4Y and O3-M122, which were previously implicated as Central Asian specific, ranged from 8.5 to 15.6%. Maternal gene flow based on mtDNA haplogroups D4c and G2a, which were previously suggested as Central Asian specific, was 8.13%.” For what it’s worth, 4% of the Y’s are R1a of the Slavic variant and 8% are R1a’s of the Indo-Iranian variant. The main issue with the latter is that some of this might be Turkified Kurds.

But what I’m really interested in is which populations modern Turks are genetically close to. In the argument of whether Turks are Greek or Armenian, these pooled Turks seem more Armenian in the heatmap. I pulled the Turk subgroups and created a table of F_st values. Nothing super surprising.

	Balkan	West	Central	North	South	East
Balkan	–	0.001	0.002	0.002	0.002	0.003
West	0.001	–	0.001	0.001	0	0.002
Central	0.002	0.001	–	0	0	0
North	0.002	0.001	0	–	0	0.001
South	0.002	0	0	0	–	0.001
East	0.003	0.002	0	0.001	0.001	–
Albanian	0	0.002	0.003	0.003	0.003	0.005
Armenian	0.004	0.002	0.001	0.001	0.001	0.001
Assyrian	0.007	0.005	0.004	0.004	0.004	0.003
Bulgarian	0	0.002	0.003	0.004	0.003	0.005
Chechen	0.007	0.006	0.006	0.006	0.006	0.006
French	0.003	0.005	0.007	0.007	0.007	0.009
Georgian	0.007	0.005	0.004	0.003	0.004	0.004
Greek	0.001	0.002	0.003	0.003	0.003	0.004
Hungarian	0.002	0.004	0.006	0.007	0.006	0.008
Iranian	0.005	0.003	0.002	0.002	0.002	0.001
Jew_Turkish	0.004	0.004	0.004	0.004	0.003	0.005
Kumyk	0.003	0.002	0.002	0.002	0.002	0.002
Lebanese	0.004	0.003	0.002	0.002	0.002	0.002
Turkmen	0.009	0.007	0.008	0.009	0.008	0.009
Ukrainian	0.003	0.006	0.008	0.009	0.009	0.01

Italian genetics in the Bronze Age

Posted on July 31, 2021July 31, 2021 by Razib Khan

A new paper on Italian Bronze Age and Iron Age genomics, Ancient genomes reveal structural shifts after the arrival of Steppe-related ancestry in the Italian Peninsula. The abstract:

Across Europe, the genetics of the Chalcolithic/Bronze Age transition is increasingly characterized in terms of an influx of Steppe-related ancestry. The effect of this major shift on the genetic structure of populations in the Italian Peninsula remains underexplored. Here, genome-wide shotgun data for 22 individuals from commingled cave and single burials in Northeastern and Central Italy dated between 3200 and 1500 BCE provide the first genomic characterization of Bronze Age individuals (n = 8; 0.001-1.2× coverage) from the central Italian Peninsula, filling a gap in the literature between 1950 and 1500 BCE. Our study confirms a diversity of ancestry components during the Chalcolithic and the arrival of Steppe-related ancestry in the central Italian Peninsula as early as 1600 BCE, with this ancestry component increasing through time. We detect close patrilineal kinship in the burial patterns of Chalcolithic commingled cave burials and a shift away from this in the Bronze Age (2200-900 BCE) along with lowered runs of homozygosity, which may reflect larger changes in population structure. Finally, we find no evidence that the arrival of Steppe-related ancestry in Central Italy directly led to changes in frequency of 115 phenotypes present in the dataset, rather that the post-Roman Imperial period had a stronger influence, particularly on the frequency of variants associated with protection against Hansen’s disease (leprosy). Our study provides a closer look at local dynamics of demography and phenotypic shifts as they occurred as part of a broader phenomenon of widespread admixture during the Chalcolithic/Bronze Age transition.

The samples pick up steppe ancestry around 1600 BC, but that’s due to a lacuna in the transect. We know now that steppe ancestry arrived in Spain and Greece before 2000 BC. It seems to me unlikely that it would be notably tardy in Italy.

Another thing I want to mention is there is clearly something West Asian (CGH-related) that is moving westward ~2000 BC in a straight shot from Anatolia to the Balkans to southern Italy. This migration seems associated with Y chromosomal lineage J2. Trying to estimate how much exogenous post-Imperial eastern ancestry is present in Southern Italians is somewhat difficult for this reason. The differences between the far south and central and northern Italy may date to the Bronze Age because of this minority component of West Asian ancestry that extended itself across the Mediterranean.

Related: my Substack piece from March on the genetic/cultural history of Italy.