Abstract

Changes in potential regulatory elements are thought to be key drivers of phenotypic divergence. However, identifying changes to regulatory elements that underlie human-specific traits has proven very challenging. Here, we use 63 reconstructed and experimentally measured DNA methylation maps of ancient and present-day humans, as well as of six chimpanzees, to detect differentially methylated regions that likely emerged in modern humans after the split from Neanderthals and Denisovans. We show that genes associated with face and vocal tract anatomy went through particularly extensive methylation changes. Specifically, we identify widespread hypermethylation in a network of face- and voice-associated genes (SOX9, ACAN, COL2A1, NFIX and XYLT1). We propose that these repression patterns appeared after the split from Neanderthals and Denisovans, and that they might have played a key role in shaping the modern human face and vocal tract.

How traits specific to modern humans have evolved is difficult to study. Here, Gokhman et al. compare measured and reconstructed DNA methylation maps of present-day humans, archaic humans and chimpanzees and find that genes that affect vocal tract and facial anatomy show methylation changes between archaic and modern humans.

Details

Title
Differential DNA methylation of vocal and facial anatomy genes in modern humans
Author
Gokhman, David 1 ; Nissim-Rafinia Malka 1 ; Agranat-Tamir Lily 2 ; Housman Genevieve 3   VIAFID ORCID Logo  ; García-Pérez, Raquel 4 ; Lizano Esther 4   VIAFID ORCID Logo  ; Cheronet Olivia 5   VIAFID ORCID Logo  ; Mallick Swapan 6 ; Nieves-Colón, Maria A 3 ; Li, Heng 7 ; Alpaslan-Roodenberg Songül 8 ; Novak, Mario 9 ; Gu Hongcang 7 ; Osinski, Jason M 10 ; Ferrando-Bernal, Manuel 4 ; Gelabert Pere 4   VIAFID ORCID Logo  ; Iddi, Lipende 11 ; Deus, Mjungu 11 ; Ivanela, Kondova 12   VIAFID ORCID Logo  ; Bontrop Ronald 12   VIAFID ORCID Logo  ; Kullmer Ottmar 13   VIAFID ORCID Logo  ; Weber, Gerhard 5 ; Shahar Tal 14 ; Dvir-Ginzberg Mona 15   VIAFID ORCID Logo  ; Faerman Marina 16 ; Quillen, Ellen E 17 ; Meissner, Alexander 18   VIAFID ORCID Logo  ; Lahav Yonatan 19 ; Kandel Leonid 20 ; Liebergall Meir 20 ; Prada, María E 21 ; Vidal, Julio M 22   VIAFID ORCID Logo  ; Gronostajski, Richard M 23   VIAFID ORCID Logo  ; Stone, Anne C 24   VIAFID ORCID Logo  ; Yakir, Benjamin 25 ; Lalueza-Fox, Carles 4   VIAFID ORCID Logo  ; Pinhasi, Ron 5   VIAFID ORCID Logo  ; Reich, David 6   VIAFID ORCID Logo  ; Marques-Bonet, Tomas 26   VIAFID ORCID Logo  ; Meshorer Eran 27   VIAFID ORCID Logo  ; Carmel Liran 1   VIAFID ORCID Logo 

1  The Hebrew University of Jerusalem, Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538) 
2  The Hebrew University of Jerusalem, Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538); The Hebrew University of Jerusalem, Department of Statistics, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538) 
3  Arizona State University, School of Human Evolution and Social Change, Tempe, USA (GRID:grid.215654.1) (ISNI:0000 0001 2151 2636); Arizona State University, Center for Evolution and Medicine, Tempe, USA (GRID:grid.215654.1) (ISNI:0000 0001 2151 2636) 
4  Institute of Evolutionary Biology (UPF-CSIC), PRBB, Barcelona, Spain (GRID:grid.418220.d) (ISNI:0000 0004 1756 6019) 
5  University of Vienna, Department of Evolutionary Anthropology, Vienna, Austria (GRID:grid.10420.37) (ISNI:0000 0001 2286 1424) 
6  Broad Institute, Cambridge, USA (GRID:grid.66859.34); Harvard Medical School, Department of Genetics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard Medical School, Howard Hughes Medical Institute, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
7  Broad Institute, Cambridge, USA (GRID:grid.66859.34) 
8  Harvard Medical School, Department of Genetics, Boston, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
9  Institute for Anthropological Research, Zagreb, Croatia (GRID:grid.418612.8); University College Dublin, Earth Institute and School of Archaeology, Dublin 4, Ireland (GRID:grid.7886.1) (ISNI:0000 0001 0768 2743) 
10  University at Buffalo, Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887) 
11  Jane Goodall Institute, Gombe Stream Research Center, Kigoma, Tanzania (GRID:grid.452808.3) 
12  Biomedical Primate Research Centre (BPRC), Rijswijk, Netherlands (GRID:grid.11184.3d) (ISNI:0000 0004 0625 2495) 
13  Senckenberg Center of Human Evolution and Paleoecology, Department of Palaeoanthropology and Messel Research, Frankfurt am Main, Germany (GRID:grid.11184.3d) 
14  Shaare Zedek Medical Center, Department of Neurosurgery, Jerusalem, Israel (GRID:grid.415593.f) (ISNI:0000 0004 0470 7791) 
15  Hebrew University of Jerusalem, Laboratory of Cartilage Biology, Institute of Dental Sciences, Faculty of Dental Medicine, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538) 
16  The Hebrew University of Jerusalem, Laboratory of Bioanthropology and Ancient DNA, Institute of Dental Sciences, Faculty of Dental Medicine, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538) 
17  Texas Biomedical Research Institute, Department of Genetics, San Antonio, USA (GRID:grid.250889.e) (ISNI:0000 0001 2215 0219) 
18  Broad Institute, Cambridge, USA (GRID:grid.66859.34); Harvard Stem Cell Institute, Cambridge, USA (GRID:grid.38142.3c) (ISNI:000000041936754X); Harvard University, Department of Stem Cell and Regenerative Biology, Cambridge, USA (GRID:grid.38142.3c) (ISNI:000000041936754X) 
19  Kaplan Medical Center, Otolaryngology - Head & Neck Surgery Department, Laryngeal Surgery Unit, Rehovot, Israel (GRID:grid.415014.5) (ISNI:0000 0004 0575 3669); The Hebrew University Medical School, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538) 
20  Hadassah – Hebrew University Medical Center, Orthopaedic Department, Jerusalem, Israel (GRID:grid.17788.31) (ISNI:0000 0001 2221 2926) 
21  I.E.S.O. ‘Los Salados’. Junta de Castilla y León, León, Spain (GRID:grid.454835.b) (ISNI:0000 0001 2192 6054) 
22  Junta de Castilla y León, Servicio de Cultura de León, León, Spain (GRID:grid.454835.b) (ISNI:0000 0001 2192 6054) 
23  University at Buffalo, Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887); University at Buffalo, Genetics, Genomics and Bioinformatics Program, New York State Center of Excellence in Bioinformatics and Life Sciences, Jacobs School of Medicine and Biomedical Sciences, Buffalo, USA (GRID:grid.273335.3) (ISNI:0000 0004 1936 9887) 
24  Arizona State University, School of Human Evolution and Social Change, Tempe, USA (GRID:grid.215654.1) (ISNI:0000 0001 2151 2636); Arizona State University, Center for Evolution and Medicine, Tempe, USA (GRID:grid.215654.1) (ISNI:0000 0001 2151 2636); Arizona State University, Institute of Human Origins, Tempe, USA (GRID:grid.215654.1) (ISNI:0000 0001 2151 2636) 
25  The Hebrew University of Jerusalem, Department of Statistics, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538) 
26  Institute of Evolutionary Biology (UPF-CSIC), PRBB, Barcelona, Spain (GRID:grid.418220.d) (ISNI:0000 0004 1756 6019); Catalan Institution of Research and Advanced Studies (ICREA), Barcelona, Spain (GRID:grid.425902.8) (ISNI:0000 0000 9601 989X); Barcelona Institute of Science and Technology (BIST), CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona, Spain (GRID:grid.473715.3); Universitat Autònoma de Barcelona, Edifici ICTA-ICP, c/ Columnes s/n, Institut Català de Paleontologia Miquel Crusafont, Barcelona, Spain (GRID:grid.7080.f) 
27  The Hebrew University of Jerusalem, Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538); The Hebrew University of Jerusalem, The Edmond and Lily Safra Center for Brain Sciences (ELSC), Jerusalem, Israel (GRID:grid.9619.7) (ISNI:0000 0004 1937 0538) 
Publication year
2020
Publication date
2020
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-020-15020-6
ProQuest document ID
2371129129
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.