Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity

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

doi:10.1016/j.cub.2018.10.065

Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity

Curr Biol. 2019 Jan 7;29(1):120-127.e5. doi: 10.1016/j.cub.2018.10.065. Epub 2018 Dec 13.

Authors

Philipp Gunz¹, Amanda K Tilot², Katharina Wittfeld³, Alexander Teumer⁴, Chin Yang Shapland², Theo G M van Erp⁵, Michael Dannemann⁶, Benjamin Vernot⁶, Simon Neubauer⁷, Tulio Guadalupe², Guillén Fernández⁸, Han G Brunner⁹, Wolfgang Enard¹⁰, James Fallon¹¹, Norbert Hosten¹², Uwe Völker¹³, Antonio Profico¹⁴, Fabio Di Vincenzo¹⁵, Giorgio Manzi¹⁴, Janet Kelso⁶, Beate St Pourcain¹⁶, Jean-Jacques Hublin⁷, Barbara Franke¹⁷, Svante Pääbo⁶, Fabio Macciardi¹⁸, Hans J Grabe¹⁹, Simon E Fisher²⁰

Affiliations

¹ Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany. Electronic address: gunz@eva.mpg.de.
² Language and Genetics Department, Max Planck Institute for Psycholinguistics, P.O. Box 310, 6500 AH, Nijmegen, the Netherlands.
³ Department of Psychiatry and Psychotherapy, University of Greifswald, Ellernholzstr. 1-2, 17489 Greifswald, Germany; German Center for Neurodegenerative Diseases (DZNE), Partner Site Rostock/Greifswald, Ellernholzstr. 1-2, 17489 Greifswald, Germany.
⁴ Institute for Community Medicine, University Medicine Greifswald, Walter-Rathenau Str. 48, 17475 Greifswald, Germany.
⁵ Clinical and Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California, Irvine, 5251 California Ave, Irvine, CA 92617, USA.
⁶ Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany.
⁷ Department of Human Evolution, Max Planck Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany.
⁸ Department of Cognitive Neuroscience, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, 6500 GA, Nijmegen, the Netherlands.
⁹ Department of Human Genetics, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, 6500 GA, Nijmegen, the Netherlands; Department of Clinical Genetics and School for Oncology & Developmental Biology (GROW), Maastricht University Medical Center, 6202 AZ, Maastricht, the Netherlands.
¹⁰ Anthropology and Human Genomics, Department Biology II, Ludwig Maximilians University Munich, Grosshaderner Str. 2, D-82152 Martinsried, Germany.
¹¹ Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA.
¹² Institute of Diagnostic Radiology and Neuroradiology, University Medicine, Ernst-Moritz-Arndt-University Greifswald, Ferdinand-Sauerbruch-Str. 1, 17475 Greifswald, Germany.
¹³ Interfaculty Institute of Genetics and Functional Genomics, Ernst-Moritz-Arndt-University Greifswald, Felix-Hausdorff-Str. 8, 17475 Greifswald, Germany.
¹⁴ Università degli Studi di Roma La Sapienza, Department of Environmental Biology, Piazzale Aldo Moro, 5, 00185, Roma, Italy.
¹⁵ Università degli Studi di Roma La Sapienza, Department of Environmental Biology, Piazzale Aldo Moro, 5, 00185, Roma, Italy; Istituto Italiano di Paleontologia Umana, Via Ulisse Aldrovandi, 18, 00197, Roma, Italy.
¹⁶ Language and Genetics Department, Max Planck Institute for Psycholinguistics, P.O. Box 310, 6500 AH, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands.
¹⁷ Donders Institute for Brain, Cognition and Behaviour, Radboud University, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands; Departments of Human Genetics and Psychiatry, Radboud University Medical Center, Nijmegen, the Netherlands.
¹⁸ Department of Psychiatry and Human Behavior, University of California, Irvine, Sprague Hall - Room 312, Gillespie Neuroscience - Laboratory, Mail Code: 3960, Irvine, CA 92697, USA.
¹⁹ Department of Psychiatry and Psychotherapy, University of Greifswald, Ellernholzstr. 1-2, 17489 Greifswald, Germany.
²⁰ Language and Genetics Department, Max Planck Institute for Psycholinguistics, P.O. Box 310, 6500 AH, Nijmegen, the Netherlands; Donders Institute for Brain, Cognition and Behaviour, Radboud University, P.O. Box 9101, 6500 HB, Nijmegen, the Netherlands. Electronic address: simon.fisher@mpi.nl.

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.

Keywords: Neandertal; basal ganglia; brain shape; cerebellum; evolution; gene expression; genetic association; homo sapiens; magnetic resonance imaging; myelination.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Aged
Aged, 80 and over
Animals
Biological Evolution*
Female
Fossils
Humans
Hybridization, Genetic*
Male
Middle Aged
Neanderthals / anatomy & histology*
Netherlands
Phenotype
Skull / anatomy & histology*
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding