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      Population genomics of Mesolithic Scandinavia: Investigating early postglacial migration routes and high-latitude adaptation

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          Abstract

          Scandinavia was one of the last geographic areas in Europe to become habitable for humans after the Last Glacial Maximum (LGM). However, the routes and genetic composition of these postglacial migrants remain unclear. We sequenced the genomes, up to 57× coverage, of seven hunter-gatherers excavated across Scandinavia and dated from 9,500–6,000 years before present (BP). Surprisingly, among the Scandinavian Mesolithic individuals, the genetic data display an east–west genetic gradient that opposes the pattern seen in other parts of Mesolithic Europe. Our results suggest two different early postglacial migrations into Scandinavia: initially from the south, and later, from the northeast. The latter followed the ice-free Norwegian north Atlantic coast, along which novel and advanced pressure-blade stone-tool techniques may have spread. These two groups met and mixed in Scandinavia, creating a genetically diverse population, which shows patterns of genetic adaptation to high latitude environments. These potential adaptations include high frequencies of low pigmentation variants and a gene region associated with physical performance, which shows strong continuity into modern-day northern Europeans.

          Author summary

          The Scandinavian peninsula was the last part of Europe to be colonized after the Last Glacial Maximum. The migration routes, cultural networks, and the genetic makeup of the first Scandinavians remain elusive and several hypotheses exist based on archaeology, climate modeling, and genetics. By analyzing the genomes of early Scandinavian hunter-gatherers, we show that their migrations followed two routes: one from the south and another from the northeast along the ice-free Norwegian Atlantic coast. These groups met and mixed in Scandinavia, creating a population more diverse than contemporaneous central and western European hunter-gatherers. As northern Europe is associated with cold and low light conditions, we investigated genomic patterns of adaptation to these conditions and genes known to be involved in skin pigmentation. We demonstrate that Mesolithic Scandinavians had higher levels of light pigmentation variants compared to the respective source populations of the migrations, suggesting adaptation to low light levels and a surprising signal of genetic continuity in TMEM131, a gene that may be involved in long-term adaptation to the cold.

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          The complete genome sequence of a Neandertal from the Altai Mountains

          We present a high-quality genome sequence of a Neandertal woman from Siberia. We show that her parents were related at the level of half siblings and that mating among close relatives was common among her recent ancestors. We also sequenced the genome of a Neandertal from the Caucasus to low coverage. An analysis of the relationships and population history of available archaic genomes and 25 present-day human genomes shows that several gene flow events occurred among Neandertals, Denisovans and early modern humans, possibly including gene flow into Denisovans from an unknown archaic group. Thus, interbreeding, albeit of low magnitude, occurred among many hominin groups in the Late Pleistocene. In addition, the high quality Neandertal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neandertals and Denisovans.
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            Ancient human genomes suggest three ancestral populations for present-day Europeans

            We sequenced genomes from a $\sim$7,000 year old early farmer from Stuttgart in Germany, an $\sim$8,000 year old hunter-gatherer from Luxembourg, and seven $\sim$8,000 year old hunter-gatherers from southern Sweden. We analyzed these data together with other ancient genomes and 2,345 contemporary humans to show that the great majority of present-day Europeans derive from at least three highly differentiated populations: West European Hunter-Gatherers (WHG), who contributed ancestry to all Europeans but not to Near Easterners; Ancient North Eurasians (ANE), who were most closely related to Upper Paleolithic Siberians and contributed to both Europeans and Near Easterners; and Early European Farmers (EEF), who were mainly of Near Eastern origin but also harbored WHG-related ancestry. We model these populations' deep relationships and show that EEF had $\sim$44% ancestry from a "Basal Eurasian" lineage that split prior to the diversification of all other non-African lineages.
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              Inferring human population size and separation history from multiple genome sequences

              The availability of complete human genome sequences from populations across the world has given rise to new population genetic inference methods that explicitly model their ancestral relationship under recombination and mutation. So far, application of these methods to evolutionary history more recent than 20-30 thousand years ago and to population separations has been limited. Here we present a new method that overcomes these shortcomings. The Multiple Sequentially Markovian Coalescent (MSMC) analyses the observed pattern of mutations in multiple individuals, focusing on the first coalescence between any two individuals. Results from applying MSMC to genome sequences from nine populations across the world suggest that the genetic separation of non-African ancestors from African Yoruban ancestors started long before 50,000 years ago, and give information about human population history as recently as 2,000 years ago, including the bottleneck in the peopling of the Americas, and separations within Africa, East Asia and Europe.
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                Author and article information

                Contributors
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: ValidationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: ValidationRole: VisualizationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: ResourcesRole: VisualizationRole: Writing – review & editing
                Role: InvestigationRole: Resources
                Role: Investigation
                Role: Data curationRole: Formal analysisRole: InvestigationRole: Validation
                Role: Investigation
                Role: Investigation
                Role: InvestigationRole: Writing – review & editing
                Role: Methodology
                Role: Resources
                Role: Resources
                Role: InvestigationRole: MethodologyRole: SoftwareRole: Visualization
                Role: InvestigationRole: MethodologyRole: SoftwareRole: Visualization
                Role: InvestigationRole: Writing – review & editing
                Role: InvestigationRole: MethodologyRole: Writing – review & editing
                Role: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: InvestigationRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: Project administrationRole: SupervisionRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, CA USA )
                1544-9173
                1545-7885
                9 January 2018
                January 2018
                9 January 2018
                : 16
                : 1
                : e2003703
                Affiliations
                [1 ] Department of Organismal Biology, Uppsala University, Uppsala, Sweden
                [2 ] Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden
                [3 ] Middle East Technical University, Department of Biological Sciences, Ankara, Turkey
                [4 ] Department of Archaeology and Ancient History, Uppsala University-Campus Gotland, Visby, Sweden
                [5 ] Norwegian Institute for Cultural Heritage Research, Oslo, Norway
                [6 ] Tromsø University Museum, University of Tromsø-The Arctic University of Norway, Tromsø, Norway
                [7 ] Department of Electrical Engineering, Center for Processing Speech and Images, Katholieke Universiteit Leuven, Leuven, Belgium
                [8 ] Department of Anthropology, Penn State University, State College, Pennsylvania, United States of America
                [9 ] Department of Archaeology and History, La Trobe University, Melbourne, Australia
                [10 ] Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands
                [11 ] Department of Archaeology and Ancient History, Lund University, Lund, Sweden
                [12 ] Department of Archaeology and Cultural History, Norwegian University of Science and Technology University Museum, Trondheim, Norway
                [13 ] SciLifeLab, Uppsala and Stockholm, Sweden
                The Institute of Science and Technology Austria, Austria
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-9460-390X
                Article
                pbio.2003703
                10.1371/journal.pbio.2003703
                5760011
                29315301
                536f6602-bf2f-4f72-a3b5-1f47d5fac07b
                © 2018 Günther et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 July 2017
                : 4 December 2017
                Page count
                Figures: 4, Tables: 1, Pages: 22
                Funding
                Berit Wallenberg foundation (grant number BWS2011.0090) to MF. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. European Research Council starting grant to MJ. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Wenner-Gren Foundations postdoctoral fellowship to TG. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Knut and Alice Wallenberg foundation to MJ, JS, AG. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Riksbankens Jubileumsfond to MJ, JS, AG. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Swedish Research council (grant number 421-2013-730) to JA, JS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Swedish Research council (grant number 2013-1905) to MJ, JS, AG. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Formas (grant number 2011-1138) to EMS. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Earth Sciences
                Geology
                Geologic Time
                Stone Age
                Mesolithic Period
                Biology and Life Sciences
                Paleontology
                Paleogenetics
                Earth Sciences
                Paleontology
                Paleogenetics
                People and Places
                Geographical Locations
                Europe
                Biology and Life Sciences
                Evolutionary Biology
                Population Genetics
                Biology and Life Sciences
                Genetics
                Population Genetics
                Biology and Life Sciences
                Population Biology
                Population Genetics
                Biology and Life Sciences
                Evolutionary Biology
                Population Genetics
                Effective Population Size
                Biology and Life Sciences
                Genetics
                Population Genetics
                Effective Population Size
                Biology and Life Sciences
                Population Biology
                Population Genetics
                Effective Population Size
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Effective Population Size
                Biology and Life Sciences
                Population Biology
                Population Metrics
                Population Size
                Effective Population Size
                Biology and Life Sciences
                Computational Biology
                Genome Analysis
                Genomic Libraries
                Biology and Life Sciences
                Genetics
                Genomics
                Genome Analysis
                Genomic Libraries
                Social Sciences
                Archaeology
                People and Places
                Population Groupings
                Ethnicities
                European People
                Norwegian People
                Custom metadata
                All sequence data generated for this project are available from the European Nucleotide Archive under the study accession number PRJEB21940. All other data are within the paper and its Supporting Information files.

                Life sciences
                Life sciences

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