Differential DNA methylation of vocal and facial anatomy genes in modern humans

David Gokhman*, Malka Nissim-Rafinia, Lily Agranat-Tamir, Genevieve Housman, Raquel García-Pérez, Esther Lizano, Olivia Cheronet, Swapan Mallick, Maria A. Nieves-Colón, Heng Li, Songül Alpaslan-Roodenberg, Mario Novak, Hongcang Gu, Jason M. Osinski, Manuel Ferrando-Bernal, Pere Gelabert, Iddi Lipende, Deus Mjungu, Ivanela Kondova, Ronald BontropOttmar Kullmer, Gerhard Weber, Tal Shahar, Mona Dvir-Ginzberg, Marina Faerman, Ellen E. Quillen, Alexander Meissner, Yonatan Lahav, Leonid Kandel, Meir Liebergall, María E. Prada, Julio M. Vidal, Richard M. Gronostajski, Anne C. Stone, Benjamin Yakir, Carles Lalueza-Fox, Ron Pinhasi, David Reich, Tomas Marques-Bonet, Eran Meshorer, Liran Carmel

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


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.

Original languageAmerican English
Article number1189
JournalNature Communications
Issue number1
StatePublished - 1 Dec 2020

Bibliographical note

Funding Information:
We would like to thank Sagiv Shifman, Yoel Rak, Rodrigo Lacruz, Erella Hovers, Anna Belfer-Cohen, Achinoam Blau, Iain Mathieson, Philip Lieberman, Daniel Lieberman, and Terry Capellini for their useful advice, Svante Pääbo, Janet Kelso, Kay Prüfer, Johannes Krause, and Anne Pusey for providing data, Sjaak Kaandorp and Christine Kaandorp-Huber from Safari park Beekse Bergen in Netherlands for their cooperation in animal conservation and use for research, and Maayan Harel for illustrations. D.G. is supported by the Clore Israel Foundation. TMB is supported by BFU2017-86471-P (MINECO/ FEDER, UE), U01 MH106874 grant, Howard Hughes International Early Career, Obra Social “La Caixa” and Secretaria d’Universitats i Recerca and CERCA Program del Departament d’Economia i Coneixement de la Generalitat de Catalunya. D.R. is an Investigator of the Howard Hughes Medical Institute and is also supported by an Allen Discovery Center for the Study of Human Brain Evolution funded the Paul G. Allen Family Foundation. C.L.-F. is supported by FEDER and BFU2015-64699-P grant from the Spanish government. R.P. was supported by ERC starting grant ADNABIOARC (263441). R.M.G. and J.M.O. are supported by NYSTEM contract C030133. Funding for the collection and processing of the 850K chimpanzee data was provided by the Leakey Foundation Research Grant for Doctoral Students, Wenner-Gren Foundation Dissertation Fieldwork Grant (Gr. 9310), James F. Nacey Fellowship from the Nacey Maggion-calda Foundation, International Primatological Society Research Grant, Sigma Xi Grant-in-Aid of Research, Center for Evolution and Medicine Venture Fund (ASU), Graduate Research and Support Program Grant (GPSA, ASU), and Graduate Student Research Grant (SHESC, ASU) to G.H. Collection of the chimpanzee bone from Tanzania was funded by the Jane Goodall Institute, and grants from the US National Institutes of Health (AI 058715) and National Science Foundation (IOS-1052693), and facilitated by Elizabeth Lonsdorf and Beatrice Hahn.

Publisher Copyright:
© 2020, The Author(s).


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