March 31, 2016

Denisovan ancestry in Oceanians (and some in South Asians)

Current Biology DOI:

The Combined Landscape of Denisovan and Neanderthal Ancestry in Present-Day Humans

Sriram Sankararaman et al.

Some present-day humans derive up to ∼5% [ 1 ] of their ancestry from archaic Denisovans, an even larger proportion than the ∼2% from Neanderthals [ 2 ]. We developed methods that can disambiguate the locations of segments of Denisovan and Neanderthal ancestry in present-day humans and applied them to 257 high-coverage genomes from 120 diverse populations, among which were 20 individual Oceanians with high Denisovan ancestry [ 3 ]. In Oceanians, the average size of Denisovan fragments is larger than Neanderthal fragments, implying a more recent average date of Denisovan admixture in the history of these populations (p = 0.00004). We document more Denisovan ancestry in South Asia than is expected based on existing models of history, reflecting a previously undocumented mixture related to archaic humans (p = 0.0013). Denisovan ancestry, just like Neanderthal ancestry, has been deleterious on a modern human genetic background, as reflected by its depletion near genes. Finally, the reduction of both archaic ancestries is especially pronounced on chromosome X and near genes more highly expressed in testes than other tissues (p = 1.2 × 10−7 to 3.2 × 10−7 for Denisovan and 2.2 × 10−3 to 2.9 × 10−3 for Neanderthal ancestry even after controlling for differences in level of selective constraint across gene classes). This suggests that reduced male fertility may be a general feature of mixtures of human populations diverged by >500,000 years.


Middle (not Upper) Paleolithic hobbits

Nature (2016) doi:10.1038/nature17179

Revised stratigraphy and chronology for Homo floresiensis at Liang Bua in Indonesia

Thomas Sutikna, Matthew W. Tocheri, Michael J. Morwood, E. Wahyu Saptomo, Jatmiko, Rokus Due Awe, Sri Wasisto, Kira E. Westaway, Maxime Aubert, Bo Li, Jian-xin Zhao, Michael Storey, Brent V. Alloway, Mike W. Morley, Hanneke J. M. Meijer, Gerrit D. van den Bergh, Rainer Grün, Anthony Dosseto, Adam Brumm, William L. Jungers & Richard G. Roberts

Homo floresiensis, a primitive hominin species discovered in Late Pleistocene sediments at Liang Bua (Flores, Indonesia)1, 2, 3, has generated wide interest and scientific debate. A major reason this taxon is controversial is because the H. floresiensis-bearing deposits, which include associated stone artefacts2, 3, 4 and remains of other extinct endemic fauna5, 6, were dated to between about 95 and 12 thousand calendar years (kyr) ago2, 3, 7. These ages suggested that H. floresiensis survived until long after modern humans reached Australia by ~50 kyr ago8, 9, 10. Here we report new stratigraphic and chronological evidence from Liang Bua that does not support the ages inferred previously for the H. floresiensis holotype (LB1), ~18 thousand calibrated radiocarbon years before present (kyr cal. BP), or the time of last appearance of this species (about 17 or 13–11 kyr cal. BP)1, 2, 3, 7, 11. Instead, the skeletal remains of H. floresiensis and the deposits containing them are dated to between about 100 and 60 kyr ago, whereas stone artefacts attributable to this species range from about 190 to 50 kyr in age. Whether H. floresiensis survived after 50 kyr ago—potentially encountering modern humans on Flores or other hominins dispersing through southeast Asia, such as Denisovans12, 13—is an open question.


March 25, 2016

Bronze Age war in northern Germany

Slaughter at the bridge: Uncovering a colossal Bronze Age battle
About 3200 years ago, two armies clashed at a river crossing near the Baltic Sea. The confrontation can’t be found in any history books—the written word didn’t become common in these parts for another 2000 years—but this was no skirmish between local clans. Thousands of warriors came together in a brutal struggle, perhaps fought on a single day, using weapons crafted from wood, flint, and bronze, a metal that was then the height of military technology.


In 1996, an amateur archaeologist found a single upper arm bone sticking out of the steep riverbank—the first clue that the Tollense Valley, about 120 kilometers north of Berlin, concealed a gruesome secret. A flint arrowhead was firmly embedded in one end of the bone, prompting archaeologists to dig a small test excavation that yielded more bones, a bashed-in skull, and a 73-centimeter club resembling a baseball bat. The artifacts all were radiocarbon-dated to about 1250 B.C.E., suggesting they stemmed from a single episode during Europe’s Bronze Age.


Northern Europe in the Bronze Age was long dismissed as a backwater, overshadowed by more sophisticated civilizations in the Near East and Greece. Bronze itself, created in the Near East around 3200 B.C.E., took 1000 years to arrive here. But Tollense’s scale suggests more organization—and more violence—than once thought. “We had considered scenarios of raids, with small groups of young men killing and stealing food, but to imagine such a big battle with thousands of people is very surprising,” says Svend Hansen, head of the German Archaeological Institute’s (DAI’s) Eurasia Department in Berlin. The well-preserved bones and artifacts add detail to this picture of Bronze Age sophistication, pointing to the existence of a trained warrior class and suggesting that people from across Europe joined the bloody fray.


There was reason for skepticism. Before Tollense, direct evidence of large-scale violence in the Bronze Age was scanty, especially in this region. Historical accounts from the Near East and Greece described epic battles, but few artifacts remained to corroborate these boastful accounts. “Even in Egypt, despite hearing many tales of war, we never find such substantial archaeological evidence of its participants and victims,” UCD’s Molloy says.


Ancient DNA could potentially reveal much more: When compared to other Bronze Age samples from around Europe at this time, it could point to the homelands of the warriors as well as such traits as eye and hair color. Genetic analysis is just beginning, but so far it supports the notion of far-flung origins. DNA from teeth suggests some warriors are related to modern southern Europeans and others to people living in modern-day Poland and Scandinavia. “This is not a bunch of local idiots,” says University of Mainz geneticist Joachim Burger. “It’s a highly diverse population.”

Long live the 25th March, 1821

March 20, 2016

Neandertal and Denisovan DNA from Melanesians

Admixture models are out of control these days, with 4 inferred archaic introgressions into three groups of Eurasians (Europeans, East Asians, Melanesians). The model on the left has to be a simplification/incomplete/wrong in some way (Melanesians are not an outgroup to Europeans and East Asians; Europeans have "Basal Eurasian" ancestry via Early European Farmers; Denisovans have some kind of weird archaic ancestry that Neandertals don't, and according to a recent study, the Altai Neandertal also has some kind of weird Proto-Modern Human lineage). In any case, this may not matter much for the problem at hand which is excavating archaic DNA from Melanesian genomes.

But, if you combined all the admixtures inferred in the literature, you'd probably need something like 8 admixtures to  model 5 populations. Time and data will show which of them are real, and reveal news ones (e.g., in Africans, who remain blissfully simple in the absence of archaic African genomes).

Science DOI: 10.1126/science.aad9416

Excavating Neandertal and Denisovan DNA from the genomes of Melanesian individuals

Benjamin Vernot et al.

Although Neandertal sequences that persist in the genomes of modern humans have been identified in Eurasians, comparable studies in people whose ancestors hybridized with both Neandertals and Denisovans are lacking. We developed an approach to identify DNA inherited from multiple archaic hominin ancestors and applied it to whole-genome sequences from 1523 geographically diverse individuals, including 35 new Island Melanesian genomes. In aggregate, we recovered 1.34 Gb and 303 Mb of the Neandertal and Denisovan genome, respectively. We leverage these maps of archaic sequence to show that Neandertal admixture occurred multiple times in different non-African populations, characterize genomic regions that are significantly depleted of archaic sequence, and identify signatures of adaptive introgression.


Adaptation in the light of ancient genomes

Nature Communications 7, Article number: 10775 doi:10.1038/ncomms10775

Human adaptation and population differentiation in the light of ancient genomes

Felix M. Key, Qiaomei Fu, Frédéric Romagné, Michael Lachmann and Aida M. Andrés

The influence of positive selection sweeps in human evolution is increasingly debated, although our ability to detect them is hampered by inherent uncertainties in the timing of past events. Ancient genomes provide snapshots of allele frequencies in the past and can help address this question. We combine modern and ancient genomic data in a simple statistic (DAnc) to time allele frequency changes, and investigate the role of drift and adaptation in population differentiation. Only 30% of the most strongly differentiated alleles between Africans and Eurasians changed in frequency during the colonization of Eurasia, but in Europe these alleles are enriched in genic and putatively functional alleles to an extent only compatible with local adaptation. Adaptive alleles—especially those associated with pigmentation—are mostly of hunter-gatherer origin, although lactose persistence arose in a haplotype present in farmers. These results provide evidence for a role of local adaptation in human population differentiation.


March 15, 2016

Preprint revolution in biology

A very nice article by Amy Harmon in the NY Times.

Handful of Biologists Went Rogue and Published Directly to Internet

On Feb. 29, Carol Greider of Johns Hopkins University became the third Nobel Prize laureate biologist in a month to do something long considered taboo among biomedical researchers: She posted a report of her recent discoveries to a publicly accessible website, bioRxiv, before submitting it to a scholarly journal to review for “official’’ publication.


And many #ASAPbio supporters retweeted John Hawks, a paleoanthropologist from the University of Wisconsin, who found himself recently at an African university where a paper on African genomes was unavailable because it could not pay the fee for the journal where it was published, and no preprint was available. He expressed his frustration with a profanity. 
Preprint advocates counter that scientists care too much about their reputations to publish shoddy work, and posts to bioRxiv are clearly marked to indicate that they may contain information that “has not yet been accepted or endorsed in any way by the scientific or medical community.’’ Others note that plenty of peer-reviewed papers in high-profile journals have proved to be wrong, and some argue that carrying out peer review after a paper is published would provide a more rigorous and fair vetting of papers, anyway.  

March 14, 2016

The dysgenic effects of modern civilization

I hope that strong AI and practical gene editing becomes a reality before this bleak future kicks in.

GENETICS March 7, 2016 vol. 202 no. 3 869-875; DOI: 10.1534/genetics.115.180471

Mutation and Human Exceptionalism: Our Future Genetic Load

Michael Lynch

Although the human germline mutation rate is higher than that in any other well-studied species, the rate is not exceptional once the effective genome size and effective population size are taken into consideration. Human somatic mutation rates are substantially elevated above those in the germline, but this is also seen in other species. What is exceptional about humans is the recent detachment from the challenges of the natural environment and the ability to modify phenotypic traits in ways that mitigate the fitness effects of mutations, e.g., precision and personalized medicine. This results in a relaxation of selection against mildly deleterious mutations, including those magnifying the mutation rate itself. The long-term consequence of such effects is an expected genetic deterioration in the baseline human condition, potentially measurable on the timescale of a few generations in westernized societies, and because the brain is a particularly large mutational target, this is of particular concern. Ultimately, the price will have to be covered by further investment in various forms of medical intervention. Resolving the uncertainties of the magnitude and timescale of these effects will require the establishment of stable, standardized, multigenerational measurement procedures for various human traits.


Sima de los Huesos hominins were Proto-Neandertals

Nature (2016) doi:10.1038/nature17405

Nuclear DNA sequences from the Middle Pleistocene Sima de los Huesos hominins

Matthias Meyer, Juan-Luis Arsuaga, Cesare de Filippo, Sarah Nagel, Ayinuer Aximu-Petri, Birgit Nickel, Ignacio Martínez, Ana Gracia, José María Bermúdez de Castro, Eudald Carbonell, Bence Viola, Janet Kelso, Kay Prüfer & Svante Pääbo

A unique assemblage of 28 hominin individuals, found in Sima de los Huesos in the Sierra de Atapuerca in Spain, has recently been dated to approximately 430,000 years ago1. An interesting question is how these Middle Pleistocene hominins were related to those who lived in the Late Pleistocene epoch, in particular to Neanderthals in western Eurasia and to Denisovans, a sister group of Neanderthals so far known only from southern Siberia. While the Sima de los Huesos hominins share some derived morphological features with Neanderthals, the mitochondrial genome retrieved from one individual from Sima de los Huesos is more closely related to the mitochondrial DNA of Denisovans than to that of Neanderthals2. However, since the mitochondrial DNA does not reveal the full picture of relationships among populations, we have investigated DNA preservation in several individuals found at Sima de los Huesos. Here we recover nuclear DNA sequences from two specimens, which show that the Sima de los Huesos hominins were related to Neanderthals rather than to Denisovans, indicating that the population divergence between Neanderthals and Denisovans predates 430,000 years ago. A mitochondrial DNA recovered from one of the specimens shares the previously described relationship to Denisovan mitochondrial DNAs, suggesting, among other possibilities, that the mitochondrial DNA gene pool of Neanderthals turned over later in their history.


March 09, 2016

Stature/body mass index and socioeconomic status

BMJ 2016; 352 doi: (Published 08 March 2016)

Height, body mass index, and socioeconomic status: mendelian randomisation study in UK Biobank 

Jessica Tyrrell, research fellow1 2, Samuel E Jones, associate research fellow1, Robin Beaumont, associate research fellow1, Christina M Astley, research fellow3 4, Rebecca Lovell, research fellow2, Hanieh Yaghootkar, research fellow1, Marcus Tuke, associate research fellow1, Katherine S Ruth, associate research fellow1, Rachel M Freathy, senior research fellow1, Joel N Hirschhorn, professor2 3 5, Andrew R Wood, research fellow1, Anna Murray, senior lecturer1, Michael N Weedon, associate professor1, Timothy M Frayling, professor1


Objective To determine whether height and body mass index (BMI) have a causal role in five measures of socioeconomic status.

Design Mendelian randomisation study to test for causal effects of differences in stature and BMI on five measures of socioeconomic status. Mendelian randomisation exploits the fact that genotypes are randomly assigned at conception and thus not confounded by non-genetic factors.

Setting UK Biobank.

Participants 119 669 men and women of British ancestry, aged between 37 and 73 years.

Main outcome measures Age completed full time education, degree level education, job class, annual household income, and Townsend deprivation index.

Results In the UK Biobank study, shorter stature and higher BMI were observationally associated with several measures of lower socioeconomic status. The associations between shorter stature and lower socioeconomic status tended to be stronger in men, and the associations between higher BMI and lower socioeconomic status tended to be stronger in women. For example, a 1 standard deviation (SD) higher BMI was associated with a £210 (€276; $300; 95% confidence interval £84 to £420; P=6×10−3) lower annual household income in men and a £1890 (£1680 to £2100; P=6×10−15) lower annual household income in women. Genetic analysis provided evidence that these associations were partly causal. A genetically determined 1 SD (6.3 cm) taller stature caused a 0.06 (0.02 to 0.09) year older age of completing full time education (P=0.01), a 1.12 (1.07 to 1.18) times higher odds of working in a skilled profession (P=6×10−7), and a £1130 (£680 to £1580) higher annual household income (P=4×10−8). Associations were stronger in men. A genetically determined 1 SD higher BMI (4.6 kg/m2) caused a £2940 (£1680 to £4200; P=1×10−5) lower annual household income and a 0.10 (0.04 to 0.16) SD (P=0.001) higher level of deprivation in women only.

Conclusions These data support evidence that height and BMI play an important partial role in determining several aspects of a person’s socioeconomic status, especially women’s BMI for income and deprivation and men’s height for education, income, and job class. These findings have important social and health implications, supporting evidence that overweight people, especially women, are at a disadvantage and that taller people, especially men, are at an advantage.