Publications by authors named "Stephen J Oppenheimer"

7 Publications

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Conservation, Extensive Heterozygosity, and Convergence of Signaling Potential All Indicate a Critical Role for KIR3DL3 in Higher Primates.

Front Immunol 2019 28;10:24. Epub 2019 Jan 28.

Division of Biomedical Informatics and Personalized Medicine, University of Colorado, Aurora, CO, United States.

Natural killer (NK) cell functions are modulated by polymorphic killer cell immunoglobulin-like receptors (KIR). Among 13 human genes, which vary by presence and copy number, is ubiquitously present in every individual across diverse populations. No ligand or function is known for KIR3DL3, but limited knowledge of expression suggests involvement in reproduction, likely during placentation. With 157 human alleles, KIR3DL3 is also highly polymorphic and we show heterozygosity exceeds that of HLA-B in many populations. The external domains of catarrhine primate KIR3DL3 evolved as a conserved lineage distinct from other KIR. Accordingly, and in contrast to other KIR, we show the focus of natural selection does not correspond exclusively to known ligand binding sites. Instead, a strong signal for diversifying selection occurs in the D1 Ig domain at a site involved in receptor aggregation, which we show is polymorphic in humans worldwide, suggesting differential ability for receptor aggregation. Meanwhile in the cytoplasmic tail, the first of two inhibitory tyrosine motifs (ITIM) is conserved, whereas independent genomic events have mutated the second ITIM of KIR3DL3 alleles in all great apes. Together, these findings suggest that KIR3DL3 binds a conserved ligand, and a function requiring both receptor aggregation and inhibitory signal attenuation. In this model KIR3DL3 resembles other NK cell inhibitory receptors having only one ITIM, which interact with bivalent downstream signaling proteins through dimerization. Due to the extensive conservation across species, selection, and other unusual properties, we consider elucidating the ligand and function of to be a pressing question.
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http://dx.doi.org/10.3389/fimmu.2019.00024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360152PMC
December 2019

Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop.

Hum Immunol 2018 Dec 12;79(12):825-833. Epub 2018 Oct 12.

Histocompatibility, Centro de Transfusión de la Comunidad de Madrid, Madrid, Spain.

The goals of the KIR component of the 17th International HLA and Immunogenetics Workshop (IHIW) were to encourage and educate researchers to begin analyzing KIR at allelic resolution, and to survey the nature and extent of KIR allelic diversity across human populations. To represent worldwide diversity, we analyzed 1269 individuals from ten populations, focusing on the most polymorphic KIR genes, which express receptors having three immunoglobulin (Ig)-like domains (KIR3DL1/S1, KIR3DL2 and KIR3DL3). We identified 13 novel alleles of KIR3DL1/S1, 13 of KIR3DL2 and 18 of KIR3DL3. Previously identified alleles, corresponding to 33 alleles of KIR3DL1/S1, 38 of KIR3DL2, and 43 of KIR3DL3, represented over 90% of the observed allele frequencies for these genes. In total we observed 37 KIR3DL1/S1 allotypes, 40 for KIR3DL2 and 44 for KIR3DL3. As KIR allotype diversity can affect NK cell function, this demonstrates potential for high functional diversity worldwide. Allelic variation further diversifies KIR haplotypes. We determined KIR3DL3 ∼ KIR3DL1/S1 ∼ KIR3DL2 haplotypes from five of the studied populations, and observed multiple population-specific haplotypes in each. This included 234 distinct haplotypes in European Americans, 191 in Ugandans, 35 in Papuans, 95 in Egyptians and 86 in Spanish populations. For another 35 populations, encompassing 642,105 individuals we focused on KIR3DL2 and identified another 375 novel alleles, with approximately half of them observed in more than one individual. The KIR allelic level data gathered from this project represents the most comprehensive summary of global KIR allelic diversity to date, and continued analysis will improve understanding of KIR allelic polymorphism in global populations. Further, the wealth of new data gathered in the course of this workshop component highlights the value of collaborative, community-based efforts in immunogenetics research, exemplified by the IHIW.
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http://dx.doi.org/10.1016/j.humimm.2018.10.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6322681PMC
December 2018

Population Turnover in Remote Oceania Shortly after Initial Settlement.

Curr Biol 2018 04 28;28(7):1157-1165.e7. Epub 2018 Feb 28.

Department of Genetics, Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Boston, MA 02115, USA; Medical and Population Genetics Program, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Max Planck-Harvard Research Center for the Archaeoscience of the Ancient Mediterranean, Cambridge, MA 02138, USA. Electronic address:

Ancient DNA from Vanuatu and Tonga dating to about 2,900-2,600 years ago (before present, BP) has revealed that the "First Remote Oceanians" associated with the Lapita archaeological culture were directly descended from the population that, beginning around 5000 BP, spread Austronesian languages from Taiwan to the Philippines, western Melanesia, and eventually Remote Oceania. Thus, ancestors of the First Remote Oceanians must have passed by the Papuan-ancestry populations they encountered in New Guinea, the Bismarck Archipelago, and the Solomon Islands with minimal admixture [1]. However, all present-day populations in Near and Remote Oceania harbor >25% Papuan ancestry, implying that additional eastward migration must have occurred. We generated genome-wide data for 14 ancient individuals from Efate and Epi Islands in Vanuatu from 2900-150 BP, as well as 185 present-day individuals from 18 islands. We find that people of almost entirely Papuan ancestry arrived in Vanuatu by around 2300 BP, most likely reflecting migrations a few hundred years earlier at the end of the Lapita period, when there is also evidence of changes in skeletal morphology and cessation of long-distance trade between Near and Remote Oceania [2, 3]. Papuan ancestry was subsequently diluted through admixture but remains at least 80%-90% in most islands. Through a fine-grained analysis of ancestry profiles, we show that the Papuan ancestry in Vanuatu derives from the Bismarck Archipelago rather than the geographically closer Solomon Islands. However, the Papuan ancestry in Polynesia-the most remote Pacific islands-derives from different sources, documenting a third stream of migration from Near to Remote Oceania.
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http://dx.doi.org/10.1016/j.cub.2018.02.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882562PMC
April 2018

Language continuity despite population replacement in Remote Oceania.

Nat Ecol Evol 2018 04 27;2(4):731-740. Epub 2018 Feb 27.

Department of Archaeogenetics, Max Planck Institute for the Science of Human History, Jena, Germany.

Recent genomic analyses show that the earliest peoples reaching Remote Oceania-associated with Austronesian-speaking Lapita culture-were almost completely East Asian, without detectable Papuan ancestry. However, Papuan-related genetic ancestry is found across present-day Pacific populations, indicating that peoples from Near Oceania have played a significant, but largely unknown, ancestral role. Here, new genome-wide data from 19 ancient South Pacific individuals provide direct evidence of a so-far undescribed Papuan expansion into Remote Oceania starting ~2,500 yr BP, far earlier than previously estimated and supporting a model from historical linguistics. New genome-wide data from 27 contemporary ni-Vanuatu demonstrate a subsequent and almost complete replacement of Lapita-Austronesian by Near Oceanian ancestry. Despite this massive demographic change, incoming Papuan languages did not replace Austronesian languages. Population replacement with language continuity is extremely rare-if not unprecedented-in human history. Our analyses show that rather than one large-scale event, the process was incremental and complex, with repeated migrations and sex-biased admixture with peoples from the Bismarck Archipelago.
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http://dx.doi.org/10.1038/s41559-018-0498-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868730PMC
April 2018

A Neolithic expansion, but strong genetic structure, in the independent history of New Guinea.

Science 2017 09;357(6356):1160-1163

Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge CB10 1SA, UK.

New Guinea shows human occupation since ~50 thousand years ago (ka), independent adoption of plant cultivation ~10 ka, and great cultural and linguistic diversity today. We performed genome-wide single-nucleotide polymorphism genotyping on 381 individuals from 85 language groups in Papua New Guinea and find a sharp divide originating 10 to 20 ka between lowland and highland groups and a lack of non-New Guinean admixture in the latter. All highlanders share ancestry within the last 10 thousand years, with major population growth in the same period, suggesting population structure was reshaped following the Neolithic lifestyle transition. However, genetic differentiation between groups in Papua New Guinea is much stronger than in comparable regions in Eurasia, demonstrating that such a transition does not necessarily limit the genetic and linguistic diversity of human societies.
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http://dx.doi.org/10.1126/science.aan3842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5802383PMC
September 2017

A genomic history of Aboriginal Australia.

Nature 2016 Oct 21;538(7624):207-214. Epub 2016 Sep 21.

Centre for GeoGenetics, Natural History Museum of Denmark, University of Copenhagen, Øster Voldgade 5-7, 1350 Copenhagen, Denmark.

The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated ~10-32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama-Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51-72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.
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http://dx.doi.org/10.1038/nature18299DOI Listing
October 2016

Do patterns of covariation between human pelvis shape, stature, and head size alleviate the obstetric dilemma?

Proc Natl Acad Sci U S A 2016 Jan 11;113(3):E258. Epub 2016 Jan 11.

School of Anthropology and Museum Ethnography, University of Oxford, Oxford OX2 6PE, United Kingdom.

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http://dx.doi.org/10.1073/pnas.1517524113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4725493PMC
January 2016
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