Search

Your search keyword '"Pääbo, Svante"' showing total 1,210 results
Start Over Author "Pääbo, Svante"
1,210 results on '"Pääbo, Svante"'

5. The molecular evolution of spermatogenesis across mammals

Author

Murat, Florent, Mbengue, Noe, Winge, Sofia Boeg, Trefzer, Timo, Leushkin, Evgeny, Sepp, Mari, Cardoso-Moreira, Margarida, Schmidt, Julia, Schneider, Celine, Mößinger, Katharina, Brüning, Thoomke, Lamanna, Francesco, Belles, Meritxell Riera, Conrad, Christian, Kondova, Ivanela, Bontrop, Ronald, Behr, Rüdiger, Khaitovich, Philipp, Pääbo, Svante, Marques-Bonet, Tomas, Grützner, Frank, Almstrup, Kristian, Schierup, Mikkel Heide, and Kaessmann, Henrik

Published
2023
Full Text
View/download PDF

6. Genetic insights into the social organization of Neanderthals

Author

Skov, Laurits, Peyrégne, Stéphane, Popli, Divyaratan, Iasi, Leonardo N. M., Devièse, Thibaut, Slon, Viviane, Zavala, Elena I., Hajdinjak, Mateja, Sümer, Arev P., Grote, Steffi, Bossoms Mesa, Alba, López Herráez, David, Nickel, Birgit, Nagel, Sarah, Richter, Julia, Essel, Elena, Gansauge, Marie, Schmidt, Anna, Korlević, Petra, Comeskey, Daniel, Derevianko, Anatoly P., Kharevich, Aliona, Markin, Sergey V., Talamo, Sahra, Douka, Katerina, Krajcarz, Maciej T., Roberts, Richard G., Higham, Thomas, Viola, Bence, Krivoshapkin, Andrey I., Kolobova, Kseniya A., Kelso, Janet, Meyer, Matthias, Pääbo, Svante, and Peter, Benjamin M.

Published
2022
Full Text
View/download PDF

7. Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity.

Author

Gunz, Philipp, Tilot, Amanda, Wittfeld, Katharina, Teumer, Alexander, Shapland, Chin, Dannemann, Michael, Vernot, Benjamin, Neubauer, Simon, Guadalupe, Tulio, Fernández, Guillén, Brunner, Han, Enard, Wolfgang, Fallon, James, Hosten, Norbert, Völker, Uwe, Profico, Antonio, Di Vincenzo, Fabio, Manzi, Giorgio, Kelso, Janet, St Pourcain, Beate, Hublin, Jean-Jacques, Franke, Barbara, Pääbo, Svante, Grabe, Hans, Fisher, Simon, Van Erp, Theodorus, and Macciardi, Fabio

Subjects
Neandertal, basal ganglia, brain shape, cerebellum, evolution, gene expression, genetic association, homo sapiens, magnetic resonance imaging, myelination, Adolescent, Adult, Aged, Aged, 80 and over, Animals, Biological Evolution, Female, Fossils, Humans, Hybridization, Genetic, Male, Middle Aged, Neanderthals, Netherlands, Phenotype, Skull, Young Adult
Abstract

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1-4]. As the endocranium closely mirrors the outer shape of the brain, these differences might reflect altered neural architecture [4, 5]. However, in the absence of fossil brain tissue, the underlying neuroanatomical changes as well as their genetic bases remain elusive. To better understand the biological foundations of modern human endocranial shape, we turn to our closest extinct relatives: the Neandertals. Interbreeding between modern humans and Neandertals has resulted in introgressed fragments of Neandertal DNA in the genomes of present-day non-Africans [6, 7]. Based on shape analyses of fossil skull endocasts, we derive a measure of endocranial globularity from structural MRI scans of thousands of modern humans and study the effects of introgressed fragments of Neandertal DNA on this phenotype. We find that Neandertal alleles on chromosomes 1 and 18 are associated with reduced endocranial globularity. These alleles influence expression of two nearby genes, UBR4 and PHLPP1, which are involved in neurogenesis and myelination, respectively. Our findings show how integration of fossil skull data with archaic genomics and neuroimaging can suggest developmental mechanisms that may contribute to the unique modern human endocranial shape.

Published
2019

10. High-throughput muscle fiber typing from RNA sequencing data

Author

Oskolkov, Nikolay, Santel, Malgorzata, Parikh, Hemang M., Ekström, Ola, Camp, Gray J., Miyamoto-Mikami, Eri, Ström, Kristoffer, Mir, Bilal Ahmad, Kryvokhyzha, Dmytro, Lehtovirta, Mikko, Kobayashi, Hiroyuki, Kakigi, Ryo, Naito, Hisashi, Eriksson, Karl-Fredrik, Nystedt, Björn, Fuku, Noriyuki, Treutlein, Barbara, Pääbo, Svante, and Hansson, Ola

Published
2022
Full Text
View/download PDF

13. A high-coverage Neandertal genome from Chagyrskaya Cave

Author

Mafessoni, Fabrizio, Grote, Steffi, de Filippo, Cesare, Slon, Viviane, Kolobova, Kseniya A., Viola, Bence, Markin, Sergey V., Chintalapati, Manjusha, Peyrégne, Stephane, Skov, Laurits, Skoglund, Pontus, Krivoshapkin, Andrey I., Derevianko, Anatoly P., Meyer, Matthias, Kelso, Janet, Peter, Benjamin, Prüfer, Kay, and Pääbo, Svante

Published
2020

15. Initial Upper Palaeolithic humans in Europe had recent Neanderthal ancestry

Author

Hajdinjak, Mateja, Mafessoni, Fabrizio, Skov, Laurits, Vernot, Benjamin, Hübner, Alexander, Fu, Qiaomei, Essel, Elena, Nagel, Sarah, Nickel, Birgit, Richter, Julia, Moldovan, Oana Teodora, Constantin, Silviu, Endarova, Elena, Zahariev, Nikolay, Spasov, Rosen, Welker, Frido, Smith, Geoff M., Sinet-Mathiot, Virginie, Paskulin, Lindsey, Fewlass, Helen, Talamo, Sahra, Rezek, Zeljko, Sirakova, Svoboda, Sirakov, Nikolay, McPherron, Shannon P., Tsanova, Tsenka, Hublin, Jean-Jacques, Peter, Benjamin M., Meyer, Matthias, Skoglund, Pontus, Kelso, Janet, and Pääbo, Svante

Published
2021
Full Text
View/download PDF

16. The Simons Genome Diversity Project: 300 genomes from 142 diverse populations

Author

Mallick, Swapan, Li, Heng, Lipson, Mark, Mathieson, Iain, Gymrek, Melissa, Racimo, Fernando, Zhao, Mengyao, Chennagiri, Niru, Nordenfelt, Susanne, Tandon, Arti, Skoglund, Pontus, Lazaridis, Iosif, Sankararaman, Sriram, Fu, Qiaomei, Rohland, Nadin, Renaud, Gabriel, Erlich, Yaniv, Willems, Thomas, Gallo, Carla, Spence, Jeffrey P, Song, Yun S, Poletti, Giovanni, Balloux, Francois, van Driem, George, de Knijff, Peter, Romero, Irene Gallego, Jha, Aashish R, Behar, Doron M, Bravi, Claudio M, Capelli, Cristian, Hervig, Tor, Moreno-Estrada, Andres, Posukh, Olga L, Balanovska, Elena, Balanovsky, Oleg, Karachanak-Yankova, Sena, Sahakyan, Hovhannes, Toncheva, Draga, Yepiskoposyan, Levon, Tyler-Smith, Chris, Xue, Yali, Abdullah, M Syafiq, Ruiz-Linares, Andres, Beall, Cynthia M, Di Rienzo, Anna, Jeong, Choongwon, Starikovskaya, Elena B, Metspalu, Ene, Parik, Jüri, Villems, Richard, Henn, Brenna M, Hodoglugil, Ugur, Mahley, Robert, Sajantila, Antti, Stamatoyannopoulos, George, Wee, Joseph TS, Khusainova, Rita, Khusnutdinova, Elza, Litvinov, Sergey, Ayodo, George, Comas, David, Hammer, Michael F, Kivisild, Toomas, Klitz, William, Winkler, Cheryl A, Labuda, Damian, Bamshad, Michael, Jorde, Lynn B, Tishkoff, Sarah A, Watkins, W Scott, Metspalu, Mait, Dryomov, Stanislav, Sukernik, Rem, Singh, Lalji, Thangaraj, Kumarasamy, Pääbo, Svante, Kelso, Janet, Patterson, Nick, and Reich, David

Subjects
Human Genome, Genetics, Animals, Australia, Black People, Datasets as Topic, Genetic Variation, Genetics, Population, Genome, Human, Genomics, History, Ancient, Human Migration, Humans, Mutation Rate, Native Hawaiian or Other Pacific Islander, Neanderthals, New Guinea, Phylogeny, Racial Groups, Sequence Analysis, DNA, Species Specificity, Time Factors, General Science & Technology
Abstract

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.

Published
2016

17. Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression

Author

Heyne, Henrike O., Lautenschläger, Susann, Nelson, Ronald, Besnier, François, Rotival, Maxime, Cagan, Alexander, Kozhemyakina, Rimma, Plyusnina, Irina Z., Trut, Lyudmila, Carlborg, Örjan, Petretto, Enrico, Kruglyak, Leonid, Pääbo, Svante, Schöneberg, Torsten, and Albert, Frank W.

Subjects
Quantitative Biology - Genomics
Abstract

Inter-individual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior towards humans for more than 64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40 and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.

Published
2014

18. A genetic analysis of the Gibraltar Neanderthals

Author

Bokelmann, Lukas, Hajdinjak, Mateja, Peyrégne, Stéphane, Brace, Selina, Essel, Elena, de Filippo, Cesare, Glocke, Isabelle, Grote, Steffi, Mafessoni, Fabrizio, Nagel, Sarah, Kelso, Janet, Prüfer, Kay, Vernot, Benjamin, Barnes, Ian, Pääbo, Svante, Meyer, Matthias, and Stringer, Chris

Published
2019

20. Ancient human genomes suggest three ancestral populations for present-day Europeans

Author

Lazaridis, Iosif, Patterson, Nick, Mittnik, Alissa, Renaud, Gabriel, Mallick, Swapan, Kirsanow, Karola, Sudmant, Peter H., Schraiber, Joshua G., Castellano, Sergi, Lipson, Mark, Berger, Bonnie, Economou, Christos, Bollongino, Ruth, Fu, Qiaomei, Bos, Kirsten I., Nordenfelt, Susanne, Li, Heng, de Filippo, Cesare, Prüfer, Kay, Sawyer, Susanna, Posth, Cosimo, Haak, Wolfgang, Hallgren, Fredrik, Fornander, Elin, Rohland, Nadin, Delsate, Dominique, Francken, Michael, Guinet, Jean-Michel, Wahl, Joachim, Ayodo, George, Babiker, Hamza A., Bailliet, Graciela, Balanovska, Elena, Balanovsky, Oleg, Barrantes, Ramiro, Bedoya, Gabriel, Ben-Ami, Haim, Bene, Judit, Berrada, Fouad, Bravi, Claudio M., Brisighelli, Francesca, Busby, George, Cali, Francesco, Churnosov, Mikhail, Cole, David E. C., Corach, Daniel, Damba, Larissa, van Driem, George, Dryomov, Stanislav, Dugoujon, Jean-Michel, Fedorova, Sardana A., Romero, Irene Gallego, Gubina, Marina, Hammer, Michael, Henn, Brenna, Hervig, Tor, Hodoglugil, Ugur, Jha, Aashish R., Karachanak-Yankova, Sena, Khusainova, Rita, Khusnutdinova, Elza, Kittles, Rick, Kivisild, Toomas, Klitz, William, Kučinskas, Vaidutis, Kushniarevich, Alena, Laredj, Leila, Litvinov, Sergey, Loukidis, Theologos, Mahley, Robert W., Melegh, Béla, Metspalu, Ene, Molina, Julio, Mountain, Joanna, Näkkäläjärvi, Klemetti, Nesheva, Desislava, Nyambo, Thomas, Osipova, Ludmila, Parik, Jüri, Platonov, Fedor, Posukh, Olga, Romano, Valentino, Rothhammer, Francisco, Rudan, Igor, Ruizbakiev, Ruslan, Sahakyan, Hovhannes, Sajantila, Antti, Salas, Antonio, Starikovskaya, Elena B., Tarekegn, Ayele, Toncheva, Draga, Turdikulova, Shahlo, Uktveryte, Ingrida, Utevska, Olga, Vasquez, René, Villena, Mercedes, Voevoda, Mikhail, Winkler, Cheryl, Yepiskoposyan, Levon, Zalloua, Pierre, Zemunik, Tatijana, Cooper, Alan, Capelli, Cristian, Thomas, Mark G., Ruiz-Linares, Andres, Tishkoff, Sarah A., Singh, Lalji, Thangaraj, Kumarasamy, Villems, Richard, Comas, David, Sukernik, Rem, Metspalu, Mait, Meyer, Matthias, Eichler, Evan E., Burger, Joachim, Slatkin, Montgomery, Pääbo, Svante, Kelso, Janet, Reich, David, and Krause, Johannes

Subjects
Quantitative Biology - Populations and Evolution
Abstract

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.

Published
2013
Full Text
View/download PDF

22. The date of interbreeding between Neandertals and modern humans

Author

Sankararaman, Sriram, Patterson, Nick, Li, Heng, Pääbo, Svante, and Reich, David

Subjects
Quantitative Biology - Populations and Evolution, Statistics - Applications
Abstract

Comparisons of DNA sequences between Neandertals and present-day humans have shown that Neandertals share more genetic variants with non-Africans than with Africans. This could be due to interbreeding between Neandertals and modern humans when the two groups met subsequent to the emergence of modern humans outside Africa. However, it could also be due to population structure that antedates the origin of Neandertal ancestors in Africa. We measure the extent of linkage disequilibrium (LD) in the genomes of present-day Europeans and find that the last gene flow from Neandertals (or their relatives) into Europeans likely occurred 37,000-86,000 years before the present (BP), and most likely 47,000-65,000 years ago. This supports the recent interbreeding hypothesis, and suggests that interbreeding may have occurred when modern humans carrying Upper Paleolithic technologies encountered Neandertals as they expanded out of Africa.

Published
2012

23. Genetic Influences on Brain Gene Expression in Rats Selected for Tameness and Aggression

Author

Heyne, Henrike O, Lautenschläger, Susann, Nelson, Ronald, Besnier, François, Rotival, Maxime, Cagan, Alexander, Kozhemyakina, Rimma, Plyusnina, Irina Z, Trut, Lyudmila, Carlborg, Örjan, Petretto, Enrico, Kruglyak, Leonid, Pääbo, Svante, Schöneberg, Torsten, and Albert, Frank W

Subjects
Genetics, Behavioral and Social Science, Mental Health, Biotechnology, Neurosciences, Basic Behavioral and Social Science, Human Genome, Aggression, Alleles, Animals, Behavior, Animal, Brain, Crosses, Genetic, Female, Gene Expression Profiling, Gene Expression Regulation, Genome, Humans, Male, Quantitative Trait Loci, RNA, Messenger, Rats, Sequence Analysis, RNA, RNA sequencing, brain gene expression, genetics of tame and aggressive behavior, natural variation, quantitative trait locus (QTL) mapping in outbred rats, q-bio.GN, Developmental Biology
Abstract

Interindividual differences in many behaviors are partly due to genetic differences, but the identification of the genes and variants that influence behavior remains challenging. Here, we studied an F2 intercross of two outbred lines of rats selected for tame and aggressive behavior toward humans for >64 generations. By using a mapping approach that is able to identify genetic loci segregating within the lines, we identified four times more loci influencing tameness and aggression than by an approach that assumes fixation of causative alleles, suggesting that many causative loci were not driven to fixation by the selection. We used RNA sequencing in 150 F2 animals to identify hundreds of loci that influence brain gene expression. Several of these loci colocalize with tameness loci and may reflect the same genetic variants. Through analyses of correlations between allele effects on behavior and gene expression, differential expression between the tame and aggressive rat selection lines, and correlations between gene expression and tameness in F2 animals, we identify the genes Gltscr2, Lgi4, Zfp40, and Slc17a7 as candidate contributors to the strikingly different behavior of the tame and aggressive animals.

Published
2014

24. Genome sequence of a 45,000-year-old modern human from western Siberia

Author

Fu, Qiaomei, Li, Heng, Moorjani, Priya, Jay, Flora, Slepchenko, Sergey M, Bondarev, Aleksei A, Johnson, Philip LF, Aximu-Petri, Ayinuer, Prüfer, Kay, de Filippo, Cesare, Meyer, Matthias, Zwyns, Nicolas, Salazar-García, Domingo C, Kuzmin, Yaroslav V, Keates, Susan G, Kosintsev, Pavel A, Razhev, Dmitry I, Richards, Michael P, Peristov, Nikolai V, Lachmann, Michael, Douka, Katerina, Higham, Thomas FG, Slatkin, Montgomery, Hublin, Jean-Jacques, Reich, David, Kelso, Janet, Viola, T Bence, and Pääbo, Svante

Subjects
Genetics, Biotechnology, Human Genome, Alleles, Animals, Chromosomes, Human, Pair 12, Diet, Evolution, Molecular, Fossils, Genome, Human, Humans, Hybridization, Genetic, Male, Molecular Sequence Data, Mutation Rate, Neanderthals, Phylogeny, Population Density, Population Dynamics, Principal Component Analysis, Sequence Analysis, DNA, Siberia, General Science & Technology
Abstract

We present the high-quality genome sequence of a ∼45,000-year-old modern human male from Siberia. This individual derives from a population that lived before-or simultaneously with-the separation of the populations in western and eastern Eurasia and carries a similar amount of Neanderthal ancestry as present-day Eurasians. However, the genomic segments of Neanderthal ancestry are substantially longer than those observed in present-day individuals, indicating that Neanderthal gene flow into the ancestors of this individual occurred 7,000-13,000 years before he lived. We estimate an autosomal mutation rate of 0.4 × 10(-9) to 0.6 × 10(-9) per site per year, a Y chromosomal mutation rate of 0.7 × 10(-9) to 0.9 × 10(-9) per site per year based on the additional substitutions that have occurred in present-day non-Africans compared to this genome, and a mitochondrial mutation rate of 1.8 × 10(-8) to 3.2 × 10(-8) per site per year based on the age of the bone.

Published
2014

25. The genomic landscape of Neanderthal ancestry in present-day humans

Author

Sankararaman, Sriram, Mallick, Swapan, Dannemann, Michael, Prüfer, Kay, Kelso, Janet, Pääbo, Svante, Patterson, Nick, and Reich, David

Subjects
Contraception/Reproduction, Clinical Research, Biotechnology, Genetics, Human Genome, Alleles, Animals, Female, Gene Flow, Genetic Predisposition to Disease, Genome, Human, Genomics, Haplotypes, Humans, Hybridization, Genetic, Infertility, Male, Keratins, Male, Neanderthals, Organ Specificity, Phylogeny, Selection, Genetic, Testis, X Chromosome, General Science & Technology
Abstract

Genomic studies have shown that Neanderthals interbred with modern humans, and that non-Africans today are the products of this mixture. The antiquity of Neanderthal gene flow into modern humans means that genomic regions that derive from Neanderthals in any one human today are usually less than a hundred kilobases in size. However, Neanderthal haplotypes are also distinctive enough that several studies have been able to detect Neanderthal ancestry at specific loci. We systematically infer Neanderthal haplotypes in the genomes of 1,004 present-day humans. Regions that harbour a high frequency of Neanderthal alleles are enriched for genes affecting keratin filaments, suggesting that Neanderthal alleles may have helped modern humans to adapt to non-African environments. We identify multiple Neanderthal-derived alleles that confer risk for disease, suggesting that Neanderthal alleles continue to shape human biology. An unexpected finding is that regions with reduced Neanderthal ancestry are enriched in genes, implying selection to remove genetic material derived from Neanderthals. Genes that are more highly expressed in testes than in any other tissue are especially reduced in Neanderthal ancestry, and there is an approximately fivefold reduction of Neanderthal ancestry on the X chromosome, which is known from studies of diverse species to be especially dense in male hybrid sterility genes. These results suggest that part of the explanation for genomic regions of reduced Neanderthal ancestry is Neanderthal alleles that caused decreased fertility in males when moved to a modern human genetic background.

Published
2014

26. Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico

Author

Williams, Amy L, Jacobs, Suzanne BR, Moreno-Macías, Hortensia, Huerta-Chagoya, Alicia, Churchhouse, Claire, Márquez-Luna, Carla, García-Ortíz, Humberto, José Gómez-Vázquez, María, Burtt, Noël P, Aguilar-Salinas, Carlos A, González-Villalpando, Clicerio, Florez, Jose C, Orozco, Lorena, Haiman, Christopher A, Tusié-Luna, Teresa, Altshuler, David, Ripke, Stephan, Manning, Alisa K, Neale, Benjamin, Reich, David, Stram, Daniel O, Fernández-López, Juan Carlos, Romero-Hidalgo, Sandra, Patterson, Nick, Aguilar-Delfín, Irma, Martínez-Hernández, Angélica, Centeno-Cruz, Federico, Mendoza-Caamal, Elvia, Revilla-Monsalve, Cristina, Islas-Andrade, Sergio, Córdova, Emilio, Rodríguez-Arellano, Eunice, Soberón, Xavier, González-Villalpando, María Elena, Henderson, Brian E, Monroe, Kristine, Wilkens, Lynne, Kolonel, Laurence N, Le Marchand, Loic, Riba, Laura, Ordóñez-Sánchez, María Luisa, Rodríguez-Guillén, Rosario, Cruz-Bautista, Ivette, Rodríguez-Torres, Maribel, Muñoz-Hernández, Linda Liliana, Sáenz, Tamara, Gómez, Donají, Alvirde, Ulices, Onofrio, Robert C, Brodeur, Wendy M, Gage, Diane, Murphy, Jacquelyn, Franklin, Jennifer, Mahan, Scott, Ardlie, Kristin, Crenshaw, Andrew T, Winckler, Wendy, Prüfer, Kay, Shunkov, Michael V, Sawyer, Susanna, Stenzel, Udo, Kelso, Janet, Lek, Monkol, Sankararaman, Sriram, MacArthur, Daniel G, Derevianko, Anatoli P, Pääbo, Svante, Gopal, Shuba, Grammatikos, James A, Smith, Ian C, Bullock, Kevin H, Deik, Amy A, Souza, Amanda L, Pierce, Kerry A, Clish, Clary B, Fennell, Timothy, and Farjoun, Yossi

Subjects
Nutrition, Diabetes, Prevention, Genetics, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Alleles, Animals, Asian People, Black People, Cohort Studies, Diabetes Mellitus, Type 2, Endoplasmic Reticulum, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Haplotypes, HeLa Cells, Humans, Indians, North American, Lipid Metabolism, Liver, Male, Mexico, Monocarboxylic Acid Transporters, Neanderthals, Polymorphism, Single Nucleotide, RNA, Messenger, Triglycerides, White People, SIGMA Type 2 Diabetes Consortium, Hela Cells, General Science & Technology
Abstract

Performing genetic studies in multiple human populations can identify disease risk alleles that are common in one population but rare in others, with the potential to illuminate pathophysiology, health disparities, and the population genetic origins of disease alleles. Here we analysed 9.2 million single nucleotide polymorphisms (SNPs) in each of 8,214 Mexicans and other Latin Americans: 3,848 with type 2 diabetes and 4,366 non-diabetic controls. In addition to replicating previous findings, we identified a novel locus associated with type 2 diabetes at genome-wide significance spanning the solute carriers SLC16A11 and SLC16A13 (P = 3.9 × 10(-13); odds ratio (OR) = 1.29). The association was stronger in younger, leaner people with type 2 diabetes, and replicated in independent samples (P = 1.1 × 10(-4); OR = 1.20). The risk haplotype carries four amino acid substitutions, all in SLC16A11; it is present at ~50% frequency in Native American samples and ~10% in east Asian, but is rare in European and African samples. Analysis of an archaic genome sequence indicated that the risk haplotype introgressed into modern humans via admixture with Neanderthals. The SLC16A11 messenger RNA is expressed in liver, and V5-tagged SLC16A11 protein localizes to the endoplasmic reticulum. Expression of SLC16A11 in heterologous cells alters lipid metabolism, most notably causing an increase in intracellular triacylglycerol levels. Despite type 2 diabetes having been well studied by genome-wide association studies in other populations, analysis in Mexican and Latin American individuals identified SLC16A11 as a novel candidate gene for type 2 diabetes with a possible role in triacylglycerol metabolism.

Published
2014

27. The complete genome sequence of a Neanderthal from the Altai Mountains

Author

Prüfer, Kay, Racimo, Fernando, Patterson, Nick, Jay, Flora, Sankararaman, Sriram, Sawyer, Susanna, Heinze, Anja, Renaud, Gabriel, Sudmant, Peter H, de Filippo, Cesare, Li, Heng, Mallick, Swapan, Dannemann, Michael, Fu, Qiaomei, Kircher, Martin, Kuhlwilm, Martin, Lachmann, Michael, Meyer, Matthias, Ongyerth, Matthias, Siebauer, Michael, Theunert, Christoph, Tandon, Arti, Moorjani, Priya, Pickrell, Joseph, Mullikin, James C, Vohr, Samuel H, Green, Richard E, Hellmann, Ines, Johnson, Philip LF, Blanche, Hélène, Cann, Howard, Kitzman, Jacob O, Shendure, Jay, Eichler, Evan E, Lein, Ed S, Bakken, Trygve E, Golovanova, Liubov V, Doronichev, Vladimir B, Shunkov, Michael V, Derevianko, Anatoli P, Viola, Bence, Slatkin, Montgomery, Reich, David, Kelso, Janet, and Pääbo, Svante

Subjects
Human Genome, Genetics, Africa, Animals, Caves, DNA Copy Number Variations, Female, Fossils, Gene Flow, Gene Frequency, Genome, Heterozygote, Humans, Inbreeding, Models, Genetic, Neanderthals, Phylogeny, Population Density, Siberia, Toe Phalanges, General Science & Technology
Abstract

We present a high-quality genome sequence of a Neanderthal 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 Neanderthal 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 Neanderthals, 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 Neanderthal genome allows us to establish a definitive list of substitutions that became fixed in modern humans after their separation from the ancestors of Neanderthals and Denisovans.

Published
2014

28. Functional synergy of a human-specific and an ape-specific metabolic regulator in human neocortex development.

Author

Lei Xing, Vasiliki Gkini, Nieminen, Anni I., Hui-Chao Zhou, Aquilino, Matilde, Naumann, Ronald, Reppe, Katrin, Kohichi Tanaka, Carmeliet, Peter, Oskari Heikinheimo, Pääbo, Svante, Huttner, Wieland B., and Takashi Namba

Abstract

Metabolism has recently emerged as a major target of genes implicated in the evolutionary expansion of human neocortex. One such gene is the humanspecific gene ARHGAP11B. During human neocortex development, ARHGAP11B increases the abundance of basal radial glia, key progenitors for neocortex expansion, by stimulating glutaminolysis (glutamine-to-glutamate-to-alphaketoglutarate) in mitochondria. Here we show that the ape-specific protein GLUD2 (glutamate dehydrogenase 2), which also operates in mitochondria and converts glutamate-to-αKG, enhances ARHGAP11B’s ability to increase basal radial glia abundance. ARHGAP11B + GLUD2 double-transgenic bRG show increased production of aspartate, a metabolite essential for cell pro-liferation, from glutamate via alpha-ketoglutarate and the TCA cycle. Hence, during human evolution, a human-specific gene exploited the existence of another gene that emerged during ape evolution, to increase, via concerted changes in metabolism, progenitor abundance and neocortex size. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

31. Age estimates for hominin fossils and the onset of the Upper Palaeolithic at Denisova Cave

Author

Douka, Katerina, Slon, Viviane, Jacobs, Zenobia, Ramsey, Christopher Bronk, Shunkov, Michael V., Derevianko, Anatoly P., Mafessoni, Fabrizio, Kozlikin, Maxim B., Li, Bo, Grün, Rainer, Comeskey, Daniel, Devièse, Thibaut, Brown, Samantha, Viola, Bence, Kinsley, Leslie, Buckley, Michael, Meyer, Matthias, Roberts, Richard G., Pääbo, Svante, Kelso, Janet, and Higham, Tom

Published
2019
Full Text
View/download PDF

32. Analysis of human accelerated DNA regions using archaic hominin genomes.

Author

Burbano, Hernán A, Green, Richard E, Maricic, Tomislav, Lalueza-Fox, Carles, de la Rasilla, Marco, Rosas, Antonio, Kelso, Janet, Pollard, Katherine S, Lachmann, Michael, and Pääbo, Svante

Subjects
Animals, Hominidae, Humans, DNA, Cluster Analysis, Adaptation, Biological, Evolution, Molecular, Mutation, Genome, Genome, Human, Male, Neanderthals, Adaptation, Biological, Evolution, Molecular, Human, General Science & Technology
Abstract

Several previous comparisons of the human genome with other primate and vertebrate genomes identified genomic regions that are highly conserved in vertebrate evolution but fast-evolving on the human lineage. These human accelerated regions (HARs) may be regions of past adaptive evolution in humans. Alternatively, they may be the result of non-adaptive processes, such as biased gene conversion. We captured and sequenced DNA from a collection of previously published HARs using DNA from an Iberian Neandertal. Combining these new data with shotgun sequence from the Neandertal and Denisova draft genomes, we determine at least one archaic hominin allele for 84% of all positions within HARs. We find that 8% of HAR substitutions are not observed in the archaic hominins and are thus recent in the sense that the derived allele had not come to fixation in the common ancestor of modern humans and archaic hominins. Further, we find that recent substitutions in HARs tend to have come to fixation faster than substitutions elsewhere in the genome and that substitutions in HARs tend to cluster in time, consistent with an episodic rather than a clock-like process underlying HAR evolution. Our catalog of sequence changes in HARs will help prioritize them for functional studies of genomic elements potentially responsible for modern human adaptations.

Published
2012

34. Genomic Sequencing of Pleistocene Cave Bears

Author

Noonan, James P., Hofreiter, Michael, Smith, Doug, Priest, James R., Rohland, Nadin, Rabeder, Gernot, Krause, Johannes, Detter, J. Chris, Pääbo, Svante, and Rubin, Edward M.

Published
2005

36. A Late Neandertal Femur from Les Rochers-de-Villeneuve, France

Author

Beauval, Cédric, Maureille, Bruno, Lacrampe-Cuyaubère, François, Serre, David, Peressinotto, David, Bordes, Jean-Guillaume, Cochard, David, Couchoud, Isabelle, Dubrasquet, David, Laroulandie, Véronique, Lenoble, Arnaud, Mallye, Jean-Baptiste, Pasty, Sylvain, Primault, Jérôme, Rohland, Nadin, Pääbo, Svante, and Trinkaus, Erik

Published
2005

38. A high-coverage Neandertal genome from Vindija Cave in Croatia

Author

Prüfer, Kay, de Filippo, Cesare, Grote, Steffi, Mafessoni, Fabrizio, Korlević, Petra, Hajdinjak, Mateja, Vernot, Benjamin, Skov, Laurits, Hsieh, Pinghsun, Peyrégne, Stéphane, Reher, David, Hopfe, Charlotte, Nagel, Sarah, Maricic, Tomislav, Fu, Qiaomei, Theunert, Christoph, Rogers, Rebekah, Skoglund, Pontus, Chintalapati, Manjusha, Dannemann, Michael, Nelson, Bradley J., Key, Felix M., Rudan, Pavao, Kućan, Željko, Gušić, Ivan, Golovanova, Liubov V., Doronichev, Vladimir B., Patterson, Nick, Reich, David, Eichler, Evan E., Slatkin, Montgomery, Schierup, Mikkel H., Andrés, Aida M., Kelso, Janet, Meyer, Matthias, and Pääbo, Svante

Published
2017

40. Neandertal and Denisovan DNA from Pleistocene sediments

Author

Slon, Viviane, Hopfe, Charlotte, Weiß, Clemens L., Mafessoni, Fabrizio, de la Rasilla, Marco, Lalueza-Fox, Carles, Rosas, Antonio, Soressi, Marie, Knul, Monika V., Miller, Rebecca, Stewart, John R., Derevianko, Anatoly P., Jacobs, Zenobia, Li, Bo, Roberts, Richard G., Shunkov, Michael V., de Lumley, Henry, Perrenoud, Christian, Gušić, Ivan, Kućan, Željko, Rudan, Pavao, Aximu-Petri, Ayinuer, Essel, Elena, Nagel, Sarah, Nickel, Birgit, Schmidt, Anna, Prüfer, Kay, Kelso, Janet, Burbano, Hernán A., Pääbo, Svante, and Meyer, Matthias

Published
2017

45. Major genetic risk factors for Dupuytren's disease are inherited from Neandertals

Author

Ågren, Richard, Patil, Snehal, Zhou, Xiang, Sahlholm, Kristoffer, Pääbo, Svante, and Zeberg, Hugo

Subjects
EPDR1, genome-wide association studies, Neandertals, splicing quantitative trait loci, risk variant, Dupuytren's disease, Medical Genetics, Medicinsk genetik
Abstract

Dupuytren's disease is characterized by fingers becoming permanently bent in a flexed position. Whereas people of African ancestry are rarely afflicted by Dupuytren's disease, up to ∼30\% of men over 60 years suffer from this condition in northern Europe. Here, we meta-analyze 3 biobanks comprising 7,871 cases and 645,880 controls and find 61 genome-wide significant variants associated with Dupuytren's disease. We show that 3 of the 61 loci harbor alleles of Neandertal origin, including the second and third most strongly associated ones (P = 6.4 × 10−132 and P = 9.2 × 10−69, respectively). For the most strongly associated Neandertal variant, we identify EPDR1 as the causal gene. Dupuytren's disease is an example of how admixture with Neandertals has shaped regional differences in disease prevalence.

Published
2023

47. Lineage-Specific Expansions of Retroviral Insertions within the Genomes of African Great Apes but Not Humans and Orangutans

Author

Yohn, Chris T, Jiang, Zhaoshi, McGrath, Sean D, Hayden, Karen E, Khaitovich, Philipp, Johnson, Matthew E, Eichler, Marla Y, McPherson, John D, Zhao, Shaying, Pääbo, Svante, and Eichler, Evan E

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Rare Diseases, Biotechnology, Human Genome, Infection, Animals, Chromosome Mapping, Endogenous Retroviruses, Gorilla gorilla, Hominidae, Humans, Introns, Molecular Sequence Data, Pan troglodytes, Pongo pygmaeus, Protein Biosynthesis, Retroelements, Species Specificity, Transcription, Genetic, Agricultural and Veterinary Sciences, Medical and Health Sciences, Developmental Biology, Agricultural, veterinary and food sciences, Biological sciences, Biomedical and clinical sciences
Abstract

Retroviral infections of the germline have the potential to episodically alter gene function and genome structure during the course of evolution. Horizontal transmissions between species have been proposed, but little evidence exists for such events in the human/great ape lineage of evolution. Based on analysis of finished BAC chimpanzee genome sequence, we characterize a retroviral element (Pan troglodytes endogenous retrovirus 1 [PTERV1]) that has become integrated in the germline of African great ape and Old World monkey species but is absent from humans and Asian ape genomes. We unambiguously map 287 retroviral integration sites and determine that approximately 95.8% of the insertions occur at non-orthologous regions between closely related species. Phylogenetic analysis of the endogenous retrovirus reveals that the gorilla and chimpanzee elements share a monophyletic origin with a subset of the Old World monkey retroviral elements, but that the average sequence divergence exceeds neutral expectation for a strictly nuclear inherited DNA molecule. Within the chimpanzee, there is a significant integration bias against genes, with only 14 of these insertions mapping within intronic regions. Six out of ten of these genes, for which there are expression data, show significant differences in transcript expression between human and chimpanzee. Our data are consistent with a retroviral infection that bombarded the genomes of chimpanzees and gorillas independently and concurrently, 3-4 million years ago. We speculate on the potential impact of such recent events on the evolution of humans and great apes.

Published
2005

50. The genome of the offspring of a Neanderthal mother and a Denisovan father

Author

Slon, Viviane, Mafessoni, Fabrizio, Vernot, Benjamin, de Filippo, Cesare, Grote, Steffi, Viola, Bence, Hajdinjak, Mateja, Peyrégne, Stéphane, Nagel, Sarah, Brown, Samantha, Douka, Katerina, Higham, Tom, Kozlikin, Maxim B., Shunkov, Michael V., Derevianko, Anatoly P., Kelso, Janet, Meyer, Matthias, Prüfer, Kay, and Pääbo, Svante

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results