May 28, 2016

British Celts have more steppe ancestry than British English

An interesting tidbit in a preprint about blood pressure genes:
We consistently obtained significantly positive f4 statistics, implying that both the modern Celtic samples and the ancient Saxon samples have more Steppe ancestry than the modern Anglo-Saxon samples from southern and eastern England. This indicates that southern and eastern England is not exclusively a genetic mix of Celts and Saxons.
Southeastern England is genetically very homogeneous. If the people there were a mix of ancient Celts and Saxons you'd expect them to be intermediate between modern Celts (who should have more Celtic ancestry than the modern English) and ancient Saxons (who should have more Saxon ancestry than the modern English).

But, it seems that the English have less steppe ancestry than both modern Celts and ancient Saxons, so they're not really intermediate. My guess is that the English have Norman ancestry that the Celts don't. While the original Normans were Scandinavians with presumably lots of steppe ancestry, I'd be surprised if the post-1066 Normans that settled England were not already heavily admixed with the "French" and so had less steppe ancestry than the modern British Celts from Wales and Scotland.


Population structure of UK Biobank and ancient Eurasians reveals adaptation at genes influencing blood pressure

Kevin Galinsky et al.

Analyzing genetic differences between closely related populations can be a powerful way to detect recent adaptation. The very large sample size of the UK Biobank is ideal for detecting selection using population differentiation, and enables an analysis of UK population structure at fine resolution. In analyses of 113,851 UK Biobank samples, population structure in the UK is dominated by 5 principal components (PCs) spanning 6 clusters: Northern Ireland, Scotland, northern England, southern England, and two Welsh clusters. Analyses with ancient Eurasians show that populations in the northern UK have higher levels of Steppe ancestry, and that UK population structure cannot be explained as a simple mixture of Celts and Saxons. A scan for unusual population differentiation along top PCs identified a genome-wide significant signal of selection at the coding variant rs601338 in FUT2 (p=9.16×10-9). In addition, by combining evidence of unusual differentiation within the UK with evidence from ancient Eurasians, we identified new genome-wide significant (p less than 5×10-8) signals of recent selection at two additional loci: CYP1A2/CSK and F12. We detected strong associations to diastolic blood pressure in the UK Biobank for the variants with new selection signals at CYP1A2/CSK (p=1.10×10-19)) and for variants with ancient Eurasian selection signals in the ATXN2/SH2B3 locus (p=8.00×10-33), implicating recent adaptation related to blood pressure.


May 27, 2016

The great migration of African Americans

PLoS Genet 12(5): e1006059. doi:10.1371/journal.pgen.1006059

The Great Migration and African-American Genomic Diversity
Soheil Baharian et al.

We present a comprehensive assessment of genomic diversity in the African-American population by studying three genotyped cohorts comprising 3,726 African-Americans from across the United States that provide a representative description of the population across all US states and socioeconomic status. An estimated 82.1% of ancestors to African-Americans lived in Africa prior to the advent of transatlantic travel, 16.7% in Europe, and 1.2% in the Americas, with increased African ancestry in the southern United States compared to the North and West. Combining demographic models of ancestry and those of relatedness suggests that admixture occurred predominantly in the South prior to the Civil War and that ancestry-biased migration is responsible for regional differences in ancestry. We find that recent migrations also caused a strong increase in genetic relatedness among geographically distant African-Americans. Long-range relatedness among African-Americans and between African-Americans and European-Americans thus track north- and west-bound migration routes followed during the Great Migration of the twentieth century. By contrast, short-range relatedness patterns suggest comparable mobility of ∼15–16km per generation for African-Americans and European-Americans, as estimated using a novel analytical model of isolation-by-distance.


May 19, 2016

35,000 year old mtDNA haplogroup U6 from Romania

I wouldn't be very surprised if many of the markers supposedly signifying recent gene flow Africa and Eurasia were actually quite old in Eurasia. The trouble is that reports of such gene flow were often based on simply observing that marker "X" occurs at a higher frequency in Africa than in Eurasia, so a common sense explanation is that it reflects limited recent gene flow between the continents. But, it is now known that common sense is not always the best guide, as e.g., ancient Europeans had mtDNA haplogroup M (in the past considered evidence of Asian admixture), Y-chromosome haplogroup C (ditto), and now U6.

The same should also apply to the Middle East where there has been admixture with Africans since the Islamic period at least. The existence of such admixture does not mean that every single lineage that occurs at low frequency in the Middle East and high frequency in Africa is diagnostic of this later period of admixture. Some of them could well be relics of old Middle Eastern populations. Who knows what people inhabited the presently inhospitable landscape of the Saharan-Arabian desert zone? The living populations can certainly make no claim to being the first ones there, but the genetic heritage of those earlier occupants may still persist in them in traces.

Similarly for the New World; in that case, there is a better case that European-looking lineages are indeed due to the colonization of the Americas over the last five centuries. However, that does not mean that all of them are, and we should be mindful of the possibility of pre-Columbian contact between the Old and New worlds.

Scientific Reports 6, Article number: 25501 (2016)

The mitogenome of a 35,000-year-old Homo sapiens from Europe supports a Palaeolithic back-migration to Africa

M. Hervella et al.

After the dispersal of modern humans (Homo sapiens) Out of Africa, hominins with a similar morphology to that of present-day humans initiated the gradual demographic expansion into Eurasia. The mitogenome (33-fold coverage) of the Peştera Muierii 1 individual (PM1) from Romania (35 ky cal BP) we present in this article corresponds fully to Homo sapiens, whilst exhibiting a mosaic of morphological features related to both modern humans and Neandertals. We have identified the PM1 mitogenome as a basal haplogroup U6*, not previously found in any ancient or present-day humans. The derived U6 haplotypes are predominantly found in present-day North-Western African populations. Concomitantly, those found in Europe have been attributed to recent gene-flow from North Africa. The presence of the basal haplogroup U6* in South East Europe (Romania) at 35 ky BP confirms a Eurasian origin of the U6 mitochondrial lineage. Consequently, we propose that the PM1 lineage is an offshoot to South East Europe that can be traced to the Early Upper Paleolithic back migration from Western Asia to North Africa, during which the U6 lineage diversified, until the emergence of the present-day U6 African lineages.


May 11, 2016

74 loci associated with educational attainment

Other than the claim in the abstract that educational attainment is "mostly environmentally determined" (*), this seems like a very useful study, as it identifies 74 loci associated with educational attainment and explores their interesting biology. 

The utility of this type of study does not consist so much in the ability to predict one's educational potential by looking at one's genotype (we're a long way off from that, and a traditional pencil-and-paper test will probably beat genetics for a long time to come). Rather, it helps move the culture forward, away from the polite ultra-egalitarianism of today's dominant worldview and towards a more scientific attitude concerning the limits of education. Such an attitude will necessarily acknowledge -whether it seems fair to us or not- that genes sometimes dictate that the smart but slothful kid should outperform his diligent but dull-witted peer.

It will certainly be very interesting to see what better methods or even larger sample sizes will bring in years to come.

(*) The heritability of educational attainment has been estimated to be 67-74% of Norwegian males of the 1940-1961 period. There is actually no "universal heritability" of a trait. In a third world country it may very well be that one's educational attainment is determined mostly by environmental effects such as whether you have access to a school within reasonable distance or to just enough food during development. In a modern country (like post-war Norway or a technologically advanced future utopia), environmental effects are expected to be minimal (as everyone will get the best of everything), and variation in educational attainment will simply be due to genes (+noise).

Nature (2016) doi:10.1038/nature17671

Genome-wide association study identifies 74 loci associated with educational attainment 

Aysu Okbay et al.

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample1, 2 of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases.


May 08, 2016

Natural selection in Britain during the last 2,000 years

The latest ancient DNA studies from the British Isles (Schiffels et al and Martiniano et al. and Cassidy et al.) support continuity over the last 2,000 years. Sure, there were continued migrations like the arrival of the Anglo-Saxons, but these were very similar groups in the grand scheme of things.

But, while ancestrally the modern Briton is probably a descendant of the Britons of 2,000 years ago with some admixture from similar continental European groups, he is not the same, as (apparently) substantial genetic adaptation has continued to operate in Britain over the same period. A new preprint by Field, Boyle, Telis et al. makes the case for adaptation in a variety of traits in the ancestors of Britons over this period. Mind you, the genetic underpinnings of many important human traits known to have high heritability are currently unknown, but there is little doubt that selection would have affected traits beyond those detected in this study. I am quite curious to see whether the striking efflorescence of cultural achievement in Britain over the last half millennium could have (at least in part) a genetic underpinning.

Depigmentation is a trait whose genetic architecture is as well as understood as any. The results of this study might surprise writers of decades and centuries past who supposed that the spectrum of pigmentation of modern Europeans was the result  of admixture-in varying measure- between Xanthochrooi and Melanchrooi races of primordial antiquity. All indications seem to be that depigmentation of hair, skin, and eyes did not co-occur in such a hypothetical race, but rather in different parts of the Caucasoid range, only reaching a high combined frequency in northern Europe to form the distinctive physical type that is distinctive of the natives of that region. It would be quite interesting to see how these traits evolved in Fennoscandia and the Baltic, regions that sport an even higher depigmentation than the British Isles. Traditionally, these areas were viewed as refuges of the Xanthochrooi but it may very well turn out to be that for whatever reason selection has acted in that area as well, as it did in the Eastern European plain where rather dark Bronze Age steppe groups gave way to rather light pigmented living eastern Slavs.

bioRxiv doi:

Detection of human adaptation during the past 2,000 years

Yair Field, Evan A Boyle, Natalie Telis, Ziyue Gao, Kyle J Gaulton, David Golan, Loic Yengo, Ghislain Rocheleau, Philippe Froguel, Mark I McCarthy, Jonathan K Pritchard

Detection of recent natural selection is a challenging problem in population genetics, as standard methods generally integrate over long timescales. Here we introduce the Singleton Density Score (SDS), a powerful measure to infer very recent changes in allele frequencies from contemporary genome sequences. When applied to data from the UK10K Project, SDS reflects allele frequency changes in the ancestors of modern Britons during the past 2,000 years. We see strong signals of selection at lactase and HLA, and in favor of blond hair and blue eyes. Turning to signals of polygenic adaptation we find, remarkably, that recent selection for increased height has driven allele frequency shifts across most of the genome. Moreover, we report suggestive new evidence for polygenic shifts affecting many other complex traits. Our results suggest that polygenic adaptation has played a pervasive role in shaping genotypic and phenotypic variation in modern humans.


May 02, 2016

Neandertal ancestry, going, going, ..., gone (?)

A deluge of new data from Upper Paleolithic Europe will give us all a lot to think about. It is incredible that Neandertal ancestry seems to have decreased over time in Europe (Oase1 is off-cline with lots of extra Neandertal ancestry from a recent genealogical Neandertal in the family tree). The functional form of the decrease seems pretty well approximated as linear.

The authors write:
Using one statistic, we estimate a decline from 4.3–5.7% from a time shortly after introgression to 1.1–2.2% in Eurasians today (Fig. 2).
This is remarkable because it shows  that most of the Neandertal ancestry of the earliest AMH in Europe was gone by the Mesolithic. It really seems that Neandertal genes were bred out of the gene pool over time. Will this trend continue into the future? Perhaps only minute traces of Neandertal DNA will remain in humans in 10,000 more years. Some of Neandertal DNA may yet prove to be neutral or beneficial, so at the limit the percentage may be more than zero. Nonetheless, the historical trend does suggest that modern humans inherited mostly genetic garbage from Neandertals and evolution is more than halfway through the process of getting rid of it.

As a corollary, there may have been other episodes of archaic admixture that are no longer detectable. Perhaps our modern human lineage has repeatedly admixed with other species, but traces of those admixtures are long gone by the action of natural selection. The reason for our relative homogeneity as a species may not be that we avoided intermixing with others, but that, sadly, most others had not much that was beneficial to offer to our ancestors.

Nature (2016) doi:10.1038/nature17993

The genetic history of Ice Age Europe

Qiaomei Fu et al.

Modern humans arrived in Europe ~45,000 years ago, but little is known about their genetic composition before the start of farming ~8,500 years ago. Here we analyse genome-wide data from 51 Eurasians from ~45,000–7,000 years ago. Over this time, the proportion of Neanderthal DNA decreased from 3–6% to around 2%, consistent with natural selection against Neanderthal variants in modern humans. Whereas there is no evidence of the earliest modern humans in Europe contributing to the genetic composition of present-day Europeans, all individuals between ~37,000 and ~14,000 years ago descended from a single founder population which forms part of the ancestry of present-day Europeans. An ~35,000-year-old individual from northwest Europe represents an early branch of this founder population which was then displaced across a broad region, before reappearing in southwest Europe at the height of the last Ice Age ~19,000 years ago. During the major warming period after ~14,000 years ago, a genetic component related to present-day Near Easterners became widespread in Europe. These results document how population turnover and migration have been recurring themes of European prehistory.