November 26, 2015

Neolithic farmers from Greece and Anatolia

A couple of new papers appeared this week. First, an article in Nature on natural selection in ancient Europe includes a sample of Anatolian Neolithic farmers and concludes that the European Neolithic farmers were descended from them with a bit of extra European hunter-gatherer admixture. Second, a new preprint on the bioRxiv includes Neolithic samples from northern Greece and finds that they too resemble the Anatolian and European farmers. I think it is time to declare the problem of "Neolithization of Europe" done. It took less than 4 years to solve it with ancient DNA. Here is a (non-exhaustive) list of papers in historical review:

Nature (2015) doi:10.1038/nature16152

Genome-wide patterns of selection in 230 ancient Eurasians

Iain Mathieson et al.

Ancient DNA makes it possible to observe natural selection directly by analysing samples from populations before, during and after adaptation events. Here we report a genome-wide scan for selection using ancient DNA, capitalizing on the largest ancient DNA data set yet assembled: 230 West Eurasians who lived between 6500 and 300 BC, including 163 with newly reported data. The new samples include, to our knowledge, the first genome-wide ancient DNA from Anatolian Neolithic farmers, whose genetic material we obtained by extracting from petrous bones, and who we show were members of the population that was the source of Europe’s first farmers. We also report a transect of the steppe region in Samara between 5600 and 300 BC, which allows us to identify admixture into the steppe from at least two external sources. We detect selection at loci associated with diet, pigmentation and immunity, and two independent episodes of selection on height.



Early farmers from across Europe directly descended from Neolithic Aegeans

Zuzana Hofmanová, Susanne Kreutzer et al.

Farming and sedentism first appear in southwest Asia during the early Holocene and later spread to neighboring regions, including Europe, along multiple dispersal routes. Conspicuous uncertainties remain about the relative roles of migration, cultural diffusion and admixture with local foragers in the early Neolithisation of Europe. Here we present paleogenomic data for five Neolithic individuals from northwestern Turkey and northern Greece, spanning the time and region of the earliest spread of farming into Europe. We observe striking genetic similarity both among Aegean early farmers and with those from across Europe. Our study demonstrates a direct genetic link between Mediterranean and Central European early farmers and those of Greece and Anatolia, extending the European Neolithic migratory chain all the way back to southwestern Asia.


November 18, 2015

Two more Denisovans (Sawyer, Renaud et al. 2015)

PNAS doi: 10.1073/pnas.1519905112

Nuclear and mitochondrial DNA sequences from two Denisovan individuals

Susanna Sawyer, Gabriel Renaud et al.

Denisovans, a sister group of Neandertals, have been described on the basis of a nuclear genome sequence from a finger phalanx (Denisova 3) found in Denisova Cave in the Altai Mountains. The only other Denisovan specimen described to date is a molar (Denisova 4) found at the same site. This tooth carries a mtDNA sequence similar to that of Denisova 3. Here we present nuclear DNA sequences from Denisova 4 and a morphological description, as well as mitochondrial and nuclear DNA sequence data, from another molar (Denisova 8) found in Denisova Cave in 2010. This new molar is similar to Denisova 4 in being very large and lacking traits typical of Neandertals and modern humans. Nuclear DNA sequences from the two molars form a clade with Denisova 3. The mtDNA of Denisova 8 is more diverged and has accumulated fewer substitutions than the mtDNAs of the other two specimens, suggesting Denisovans were present in the region over an extended period. The nuclear DNA sequence diversity among the three Denisovans is comparable to that among six Neandertals, but lower than that among present-day humans.


November 16, 2015

West_Asian in the flesh (hunter-gatherers from Georgia) (Jones et al. 2015)

Years ago, I detected the presence of a West_Asian genetic component (with dual modes in "Caucasus" and "Gedrosia") whose origins I placed in the "highlands of West Asia" and which I proposed spread into Europe post-5kya with Indo-European languages.

Earlier this year, the study by Haak et al. showed that steppe invaders after 5kya brought into Europe a 50/50 mix of "Eastern European Hunter-Gatherer" (EHG) ancestry/An unknown population from the Near East/Caucasus. The "unknown population" was most similar to Caucasians/Near Easterners like Armenians but did not correspond to any ancient sample.

A new paper in Nature Communications by Jones et al. finds this "missing link" in the flesh in Upper Paleolithic/Mesolithic hunter-gatherers from Georgia which they call "Caucasus Hunter-Gatherers" (CHG). From the paper:
The separation between CHG and both EF and WHG ended during the Early Bronze Age when a major ancestral component linked to CHG was carried west by migrating herders from the Eurasian Steppe. The foundation group for this seismic change was the Yamnaya, who we estimate to owe half of their ancestry to CHG-linked sources.
The authors also make the connection to South Asia:
In modern populations, the impact of CHG also stretches beyond Europe to the east. Central and South Asian populations received genetic influx from CHG (or a population close to them), as shown by a prominent CHG component in ADMIXTURE (Supplementary Fig. 5; Supplementary Note 9) and admixture f3-statistics, which show many samples as a mix of CHG and another South Asian population (Fig. 4b; Supplementary Table 9).
Also of interest:
Both Georgian hunter-gatherer samples were assigned to haplogroup J with Kotias belonging to the subhaplogroup J2a (see methods).
The paper is open access, so go ahead and read it for other details.

Nature Communications 6, Article number: 8912 doi:10.1038/ncomms9912

Upper Palaeolithic genomes reveal deep roots of modern Eurasians

Eppie R. Jones et al.

We extend the scope of European palaeogenomics by sequencing the genomes of Late Upper Palaeolithic (13,300 years old, 1.4-fold coverage) and Mesolithic (9,700 years old, 15.4-fold) males from western Georgia in the Caucasus and a Late Upper Palaeolithic (13,700 years old, 9.5-fold) male from Switzerland. While we detect Late Palaeolithic–Mesolithic genomic continuity in both regions, we find that Caucasus hunter-gatherers (CHG) belong to a distinct ancient clade that split from western hunter-gatherers ~45 kya, shortly after the expansion of anatomically modern humans into Europe and from the ancestors of Neolithic farmers ~25 kya, around the Last Glacial Maximum. CHG genomes significantly contributed to the Yamnaya steppe herders who migrated into Europe ~3,000 BC, supporting a formative Caucasus influence on this important Early Bronze age culture. CHG left their imprint on modern populations from the Caucasus and also central and south Asia possibly marking the arrival of Indo-Aryan languages.


November 11, 2015

Genetic structure of 1,272 Italians

From the paper:
The distribution of the pairwise Fst distances between all population pairs is shown in Supplementary Table S3. The genetic distance between Southern and Northern Italians (Fst=0.0013) is comparable to that between individuals living in different political units (ie, Iberians-Romanians Fst=0.0011; British-French Fst=0.0007), and, interestingly, in >50% of all the possible pairwise comparisons within Europe (Supplementary Figure S7).
European Journal of Human Genetics advance online publication 11 November 2015; doi: 10.1038/ejhg.2015.233

The Italian genome reflects the history of Europe and the Mediterranean basin

Giovanni Fiorito et al.

Recent scientific literature has highlighted the relevance of population genetic studies both for disease association mapping in admixed populations and for understanding the history of human migrations. Deeper insight into the history of the Italian population is critical for understanding the peopling of Europe. Because of its crucial position at the centre of the Mediterranean basin, the Italian peninsula has experienced a complex history of colonization and migration whose genetic signatures are still present in contemporary Italians. In this study, we investigated genomic variation in the Italian population using 2.5 million single-nucleotide polymorphisms in a sample of more than 300 unrelated Italian subjects with well-defined geographical origins. We combined several analytical approaches to interpret genome-wide data on 1272 individuals from European, Middle Eastern, and North African populations. We detected three major ancestral components contributing different proportions across the Italian peninsula, and signatures of continuous gene flow within Italy, which have produced remarkable genetic variability among contemporary Italians. In addition, we have extracted novel details about the Italian population’s ancestry, identifying the genetic signatures of major historical events in Europe and the Mediterranean basin from the Neolithic (e.g., peopling of Sardinia) to recent times (e.g., ‘barbarian invasion’ of Northern and Central Italy). These results are valuable for further genetic, epidemiological and forensic studies in Italy and in Europe.


November 04, 2015

Selection against Neandertal deleterious alleles

Sampled Neandertals (from Europe, the Caucasus, and Siberia) certainly had lower effective population size than living humans, but I wonder what the comparison would be between ancient tribes of modern humans and Neandertals in the Near East where admixture presumably took place.


The Genetic Cost of Neanderthal Introgression

Kelley Harris, Rasmus Nielsen

Approximately 2-4% of the human genome is in non-Africans comprised of DNA intro- gressed from Neanderthals. Recent studies have shown that there is a paucity of introgressed DNA around functional regions, presumably caused by selection after introgression. This observation has been suggested to be a possible consequence of the accumulation of a large amount of Dobzhansky-Muller incompatibilities, i.e. epistatic effects between human and Neanderthal specific mutations, since the divergence of humans and Neanderthals approx. 400-600 kya. However, using previously published estimates of inbreeding in Neanderthals, and of the distribution of fitness effects from human protein coding genes, we show that the average Neanderthal would have had at least 40% lower fitness than the average human due to higher levels of inbreeding and an increased mutational load, regardless of the dominance coefficients of new mutations. Using simulations, we show that under the assumption of additive dominance effects, early Neanderthal/human hybrids would have experienced strong negative selection, though not so strong that it would prevent Neanderthal DNA from entering the human population. In fact, the increased mutational load in Neanderthals predicts the observed reduction in Neanderthal introgressed segments around protein coding genes, without any need to invoke epistasis. The simulations also predict that there is a residual Neanderthal derived mutational load in non-African humans, leading to an average fitness reduction of at least 0.5%. Although there has been much previous debate about the effects of the out-of-Africa bottleneck on mutational loads in non-Africans, the significant deleterious effects of Neanderthal introgression have hitherto been left out of this discussion, but might be just as important for understanding fitness differences among human populations. We also show that if deleterious mutations are recessive, the Neanderthal admixture fraction would gradually increase over time due to selection for Neanderthal haplotypes that mask human deleterious mutations in the heterozygous state. This effect of dominance heterosis might partially explain why adaptive introgression appears to be widespread in nature.



The Strength of Selection Against Neanderthal Introgression

Ivan Juric, Simon Aeschbacher, Graham Coop

Hybridization between humans and Neanderthals has resulted in a low level of Neanderthal ancestry scattered across the genomes of many modern-day humans. After hybridization, on average, selection appears to have removed Neanderthal alleles from the human population. Quantifying the strength and causes of this selection against Neanderthal ancestry is key to understanding our relationship to Neanderthals and, more broadly, how populations remain distinct after secondary contact. Here, we develop a novel method for estimating the genome-wide average strength of selection and the density of selected sites using estimates of Neanderthal allele frequency along the genomes of modern-day humans. We confirm that East Asians had somewhat higher initial levels of Neanderthal ancestry than Europeans even after accounting for selection. We find that there are systematically lower levels of initial introgression on the X chromosome, a finding consistent with a strong sex bias in the initial matings between the populations. We find that the bulk of purifying selection against Neanderthal ancestry is best understood as acting on many weakly deleterious alleles. We propose that the majority of these alleles were effectively neutral-and segregating at high frequency-in Neanderthals, but became selected against after entering human populations of much larger effective size. While individually of small effect, these alleles potentially imposed a heavy genetic load on the early-generation human-Neanderthal hybrids. This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought.