By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization’s decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages.

SummaryWe report genome-wide ancient DNA from 49 individuals forming four parallel time transects in Belize, Brazil, the Central Andes, and the Southern Cone, each dating to at least ∼9,000 years ago. The common ancestral population radiated rapidly from just one of the two early branches that contributed to Native Americans today. We document two previously unappreciated streams of gene flow between North and South America. One affected the Central Andes by ∼4,200 years ago, while the other explains an affinity between the oldest North American genome associated with the Clovis culture and the oldest Central and South Americans from Chile, Brazil, and Belize. However, this was not the primary source for later South Americans, as the other ancient individuals derive from lineages without specific affinity to the Clovis-associated genome, suggesting a population replacement that began at least 9,000 years ago and was followed by substantial population continuity in multiple regions.

Bell Beaker pottery spread across western and central Europe beginning around 2750 BCE before disappearing between 2200–1800 BCE. The forces propelling its expansion are a matter of long-standing debate, with support for both cultural diffusion and migration. We present new genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 Beaker-associated individuals. We detected limited genetic affinity between Iberian and central European Beaker-associated individuals, and thus exclude migration as a significant mechanism of spread between these two regions. However, migration played a key role in the further dissemination of the Beaker Complex, a phenomenon we document most clearly in Britain, where the spread of the Beaker Complex introduced high levels of Steppe-related ancestry and was associated with a replacement of ~90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought Steppe-related ancestry into central and northern Europe 400 years earlier.

Summary Embryonic development relies on the capacity of progenitor cells to appropriately respond to inductive cues; a cellular property known as developmental competence. Here we report that epigenetic priming of enhancers signifies developmental competence during endodermal lineage diversification. Chromatin mapping during pancreatic and hepatic differentiation of human embryonic stem cells revealed the en masse acquisition of a poised chromatin state at enhancers specific to endoderm-derived cell lineages in gut tube intermediates. Experimentally, the acquisition of this poised enhancer state predicts the ability of endodermal intermediates to respond to inductive signals. Furthermore, these enhancers are first recognized by the pioneer transcription factors FOXA1 and FOXA2 when competence is acquired, while subsequent recruitment of lineage-inductive transcription factors, such as PDX1, leads to enhancer and target gene activation. Together, our results identify the acquisition of a poised chromatin state at enhancers as a mechanism by which progenitor cells acquire developmental competence.

Paleo-Eskimos were the first people to settle vast regions of the American Arctic around 5,000 years ago, and were subsequently joined and largely displaced around 1,000 years ago by ancestors of present-day Inuit and Yup’ik1–3. The genetic relationship between Paleo-Eskimos and Native American, Inuit, Yup’ik and Aleut populations remains uncertain4–7. Here we present new genomic data for 48 ancient individuals from Chukotka, East Siberia, the Aleutian Islands, Alaska, and the Canadian Arctic. We co-analyze these data with new data from present-day Alaskan Iñupiat and West Siberian populations and published genomes. Employing new methods based on rare allele and haplotype sharing as well as established methods4,8–10, we show that Paleo-Eskimo-related ancestry is ubiquitous among populations speaking Na-Dene and Eskimo-Aleut languages. We develop a comprehensive model for the Holocene peopling events of Chukotka and North America, and show that several key migrations connected to the origin of the Na-Dene peoples, the peopling of the Aleutian Islands, and the spread of Yup’ik and Inuit across the Arctic region are genetically linked to a single Siberian source related to Paleo-Eskimos.