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

Adult Aged Animals Cells, Cultured Child Chondrocytes DNA Methylation DNA, Ancient Evolution, Molecular Face / anatomy & histology Female Gene Regulatory Networks Genetic Speciation Humans Larynx / anatomy & histology Male Middle Aged Neanderthals / genetics Pan troglodytes / genetics Phenotype Phonation / genetics Primary Cell Culture Tongue / anatomy & histology Vocal Cords / anatomy & histology Vocalization, Animal

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
04 03 2020
Historique:
received: 25 02 2019
accepted: 13 02 2020
entrez: 6 3 2020
pubmed: 7 3 2020
medline: 27 6 2020
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.1038/s41467-020-15020-6 PMID: 32132541 PMC: PMC7055320
pubmed: 32132541
doi: 10.1038/s41467-020-15020-6
pii: 10.1038/s41467-020-15020-6
pmc: PMC7055320
doi:

Substances chimiques

DNA, Ancient 0

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1189

Subventions

Organisme : NIH HHS
ID : P51 OD011133
Pays : United States
Organisme : Howard Hughes Medical Institute
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH106874
Pays : United States

Références

Prüfer, K. et al. The complete genome sequence of a Neanderthal from the Altai Mountains. Nature 505, 43–49 (2014).
doi: 10.1038/nature12886 pubmed: 24352235 pmcid: 24352235
King, M. C. & Wilson, A. C. Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975).
doi: 10.1126/science.1090005 pubmed: 1090005 pmcid: 1090005
Hernando-Herraez, I., Garcia-Perez, R., Sharp, A. J. & Marques-Bonet, T. DNA methylation: insights into human evolution. PLoS Genet. 11, (2015).
Gokhman, D. et al. Reconstructing the DNA methylation maps of the Neandertal and the Denisovan. Science 344, 523–527 (2014).
Prüfer, K. et al. A high-coverage Neandertal genome from Vindija Cave in Croatia. Science 358, 655–658 (2017).
doi: 10.1126/science.aao1887 pubmed: 28982794 pmcid: 28982794
Fu, Q. et al. Genome sequence of a 45,000-year-old modern human from western Siberia. Nature 514, 445–449 (2014).
doi: 10.1038/nature13810 pubmed: 25341783 pmcid: 25341783
Lazaridis, I. et al. Ancient human genomes suggest three ancestral populations for present-day Europeans. Nature 513, 409–413 (2014).
doi: 10.1038/nature13673 pubmed: 25230663 pmcid: 25230663
Olalde, I. et al. Derived immune and ancestral pigmentation alleles in a 7,000-year-old Mesolithic European. Nature 507, 225–228 (2014).
doi: 10.1038/nature12960 pubmed: 24463515 pmcid: 24463515
Mathieson, I. et al. Genome-wide patterns of selection in 230 ancient Eurasians. Nature 528, 499–503 (2015).
doi: 10.1038/nature16152 pubmed: 26595274 pmcid: 26595274
Gokhman, D., Malul, A. & Carmel, L. Inferring past environments from ancient epigenomes. Mol. Biol. Evol. 34, 2429–2438 (2017).
doi: 10.1093/molbev/msx211 pubmed: 28957511 pmcid: 28957511
Gokhman, D. et al. Gene ORGANizer: linking genes to the organs they affect. Nucleic Acids Res. 45, W138–W145 (2017).
doi: 10.1093/nar/gkx302 pubmed: 28444223 pmcid: 28444223
Aiello, L. & Dean, C. An Introduction to Human Evolutionary Anatomy (Elsevier, 2002).
Prescott, S. L. et al. Enhancer divergence and cis-regulatory evolution in the human and chimp neural crest. Cell 163, 68–84 (2015).
doi: 10.1016/j.cell.2015.08.036 pubmed: 26365491 pmcid: 26365491
Wilderman, A., VanOudenhove, J., Kron, J., Noonan, J. P. & Cotney, J. High-resolution epigenomic Atlas of human embryonic craniofacial development. Cell Rep. 23, 1581–1597 (2018).
doi: 10.1016/j.celrep.2018.03.129 pubmed: 29719267 pmcid: 29719267
MacArthur, J. et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 45, D896–D901 (2017).
doi: 10.1093/nar/gkw1133 pubmed: 27899670 pmcid: 27899670
Hernando-Herraez, I. et al. The interplay between DNA methylation and sequence divergence in recent human evolution. Nucleic Acids Res. 43, 8204–8214 (2015).
doi: 10.1093/nar/gkv693 pubmed: 26170231 pmcid: 26170231
Schultz, M. D. et al. Human body epigenome maps reveal noncanonical DNA methylation variation. Nature 523, 212–216 (2015).
doi: 10.1038/nature14465 pubmed: 26030523 pmcid: 26030523
Peyrégne, S., Boyle, M. J., Dannemann, M. & Prüfer, K. Detecting ancient positive selection in humans using extended lineage sorting. Genome Res. 27, 1563–1572 (2017).
doi: 10.1101/gr.219493.116 pubmed: 28720580 pmcid: 28720580
Köhler, S. et al. The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data. Nucleic Acids Res. 42, D966–D974 (2014).
Lee, Y. H. & Saint-Jeannet, J. P. Sox9 function in craniofacial development and disease. Genesis 49, 200–208 (2011).
doi: 10.1002/dvg.20717 pubmed: 21309066 pmcid: 21309066
Ng, L. J. et al. Sox9 binds DNA, activates transcription, and coexpresses with type II collagen during chondrogenesis in the mouse. Dev. Biol. 183, 108–121 (1997).
doi: 10.1006/dbio.1996.8487 pubmed: 9119111 pmcid: 9119111
Claes, P. et al. Genome-wide mapping of global-to-local genetic effects on human facial shape. Nat. Genet. 50, 414–423 (2018).
doi: 10.1038/s41588-018-0057-4 pubmed: 29459680 pmcid: 29459680
Yao, B. et al. The SOX9 upstream region prone to chromosomal aberrations causing campomelic dysplasia contains multiple cartilage enhancers. Nucleic Acids Res. 43, 5394–5408 (2015).
doi: 10.1093/nar/gkv426 pubmed: 25940622 pmcid: 25940622
Kim, K. Il, Park, Y. S. & Im, G. Il Changes in the epigenetic status of the SOX-9 promoter in human osteoarthritic cartilage. J. Bone Miner. Res. 28, 1050–1060 (2013).
doi: 10.1002/jbmr.1843 pubmed: 23225119 pmcid: 23225119
Claes, P. et al. Modeling 3D facial shape from DNA. PLoS Genet. 10, e1004224 (2014).
doi: 10.1371/journal.pgen.1004224 pubmed: 24651127 pmcid: 24651127
Cheng, P. F. et al. Methylation-dependent SOX9 expression mediates invasion in human melanoma cells and is a negative prognostic factor in advanced melanoma. Genome Biol. 16, 42 (2015).
doi: 10.1186/s13059-015-0594-4 pubmed: 25885555 pmcid: 25885555
Huang, C.-Z. et al. Sox9 transcriptionally regulates Wnt signaling in intestinal epithelial stem cells in hypomethylated crypts in the diabetic state. Stem Cell Res. Ther. 8, 60 (2017).
doi: 10.1186/s13287-017-0507-4 pubmed: 28279198 pmcid: 28279198
Pamnani, M., Sinha, P., Singh, A., Nara, S. & Sachan, M. Methylation of the Sox9 and Oct4 promoters and its correlation with gene expression during testicular development in the laboratory mouse. Genet. Mol. Biol. 39, 452–458 (2016).
doi: 10.1590/1678-4685-GMB-2015-0172 pubmed: 27560488 pmcid: 27560488
Hall, B. D. Lethality in Desbuquois dysplasia: three new cases. Pediatr. Radiol. 31, 43–47 (2001).
doi: 10.1007/s002470000358 pubmed: 11200998 pmcid: 11200998
LaCroix, A. J. et al. GGC repeat expansion and exon 1 methylation of XYLT1 Is a common pathogenic variant in Baratela-Scott syndrome. Am. J. Hum. Genet. 104, 35–44 (2019).
doi: 10.1016/j.ajhg.2018.11.005 pubmed: 30554721 pmcid: 30554721
Ohba, S., He, X., Hojo, H. & McMahon, A. P. Distinct transcriptional programs underlie Sox9 regulation of the mammalian chondrocyte. Cell Rep. 12, 229–243 (2015).
doi: 10.1016/j.celrep.2015.06.013 pubmed: 26146088 pmcid: 26146088
Gokhman, D. et al. Reconstructing Denisovan anatomy using DNA methylation maps. Cell 179, 180–192 (2019).
doi: 10.1016/j.cell.2019.08.035 pubmed: 31539495 pmcid: 31539495
Roadmap Epigenomics Consortium. et al. Integrative analysis of 111 reference human epigenomes. Nature 518, 317–329 (2015).
doi: 10.1038/nature14248
Carrió, E. et al. Deconstruction of DNA methylation patterns during myogenesis reveals specific epigenetic events in the establishment of the skeletal muscle lineage. Stem Cells 33, 2025–2036 (2015).
doi: 10.1002/stem.1998 pubmed: 25801824 pmcid: 25801824
Maunakea, A. K. et al. Conserved role of intragenic DNA methylation in regulating alternative promoters. Nature 466, 253–257 (2010).
doi: 10.1038/nature09165 pubmed: 20613842 pmcid: 20613842
Ford, E. E. et al. Frequent lack of repressive capacity of promoter DNA methylation identified through genome-wide epigenomic manipulation. Preprint at bioRxiv https://doi.org/10.1101/170506 (2018).
Housman, G., Havill, L. M., Quillen, E. E., Comuzzie, A. G. & Stone, A. C. Assessment of DNA methylation patterns in the bone and cartilage of a nonhuman primate model of osteoarthritis. Cartilage 10, 335–345 (2018).
Pjanic, M. et al. Nuclear Factor I genomic binding associates with chromatin boundaries. BMC Genomics 14, 99 (2013).
doi: 10.1186/1471-2164-14-99 pubmed: 23402308 pmcid: 23402308
Tompson, S. W. et al. A recessive skeletal dysplasia, SEMD aggrecan type, results from a missense mutation affecting the C-type lectin domain of aggrecan. Am. J. Hum. Genet. 84, 72–79 (2009).
doi: 10.1016/j.ajhg.2008.12.001 pubmed: 19110214 pmcid: 19110214
Frenzel, K., Amann, G. & Lubec, B. Deficiency of laryngeal collagen type II in an infant with respiratory problems. Arch. Dis. Child. 78, 557–559 (1998).
doi: 10.1136/adc.78.6.557 pubmed: 9713015 pmcid: 9713015
Hoornaert, K. P. et al. Stickler syndrome caused by COL2A1 mutations: genotype–phenotype correlation in a series of 100 patients. Eur. J. Hum. Genet. 18, 872–880 (2010).
doi: 10.1038/ejhg.2010.23 pubmed: 20179744 pmcid: 20179744
Shaw, A. C. et al. Phenotype and natural history in Marshall-Smith syndrome. Am. J. Med. Genet. A 152, 2714–2726 (2010).
doi: 10.1002/ajmg.a.33709
Gokhman, D., Meshorer, E. & Carmel, L. Epigenetics: it’s getting old. past meets future in paleoepigenetics. Trends Ecol. Evol. 31, 290–300 (2016).
Lieberman, P. The evolution of human speech: its anatomical and neural bases. Curr. Anthropol. 48, 39–66 (2007).
doi: 10.1086/509092
Fitch, W. T., de Boer, B., Mathur, N. & Ghazanfar, A. Response to Lieberman on “Monkey vocal tracts are speech-ready”. Sci. Adv. 3, e1701859 (2017).
Boë, L.-J. et al. Which way to the dawn of speech?: Reanalyzing half a century of debates and data in light of speech science. Sci. Adv. 5, eaaw3916 (2019).
doi: 10.1126/sciadv.aaw3916 pubmed: 32076631 pmcid: 32076631
Lieberman, P. Comment on “Monkey vocal tracts are speech-ready”. Sci. Adv. 3, e1700442 (2017).
Lieberman, D. E. The Evolution of the Human Head (Harvard Univ. Press, 2011).
Nishimura, T., Mikami, A., Suzuki, J. & Matsuzawa, T. Descent of the hyoid in chimpanzees: evolution of face flattening and speech. J. Hum. Evol. 51, 244–254 (2006).
doi: 10.1016/j.jhevol.2006.03.005 pubmed: 16730049 pmcid: 16730049
Fitch, W. T. The evolution of speech: a comparative review. Trends Cogn. Sci. 4, 258–267 (2000).
doi: 10.1016/S1364-6613(00)01494-7 pubmed: 10859570 pmcid: 10859570
Steele, J., Clegg, M. & Martelli, S. Comparative morphology of the hominin and african ape hyoid bone, a possible marker of the evolution of speech. Hum. Biol. 85, 639–672 (2013).
doi: 10.3378/027.085.0501 pubmed: 25078953 pmcid: 25078953
Malan, V. et al. Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a sotos-like or a Marshall-Smith Syndrome. Am. J. Hum. Genet. 87, 189–198 (2010).
doi: 10.1016/j.ajhg.2010.07.001 pubmed: 20673863 pmcid: 20673863
Van Balkom, I. D. C. et al. Development and behaviour in Marshall-Smith syndrome: an exploratory study of cognition, phenotype and autism. J. Intellect. Disabil. Res. 55, 973–987 (2011).
Qiu, Y. et al. Oligogenic effects of 16p11.2 copy number variation on craniofacial development. Cell Rep. 28, 3320–3328.e4 (2019).
Cullen á, A., Clarke á, T. A. & O’Dwyer, T. P. The Marshall-Smith syndrome: a review of the laryngeal complications. Eur. J. Pediatr. 156, 463–464 (1997).
doi: 10.1007/s004310050640 pubmed: 9208244 pmcid: 9208244
Ziller, M. J. et al. Charting a dynamic DNA methylation landscape of the human genome. Nature 500, 477–481 (2013).
doi: 10.1038/nature12433 pubmed: 23925113 pmcid: 23925113
Håkelien, A. M. et al. The regulatory landscape of osteogenic differentiation. Stem Cells 32, 2780–2793 (2014).
doi: 10.1002/stem.1759 pubmed: 24898411 pmcid: 24898411
Bernstein, B. E. et al. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).
doi: 10.1038/nature11247
Moriarity, B. S. et al. A sleeping beauty forward genetic screen identifies new genes and pathways driving osteosarcoma development and metastasis. Nat. Genet. 47, 615–624 (2015).
doi: 10.1038/ng.3293 pubmed: 25961939 pmcid: 25961939
Lacruz, R. S. et al. Ontogeny of the maxilla in Neanderthals and their ancestors. Nat. Commun. 6, 8996 (2015).
doi: 10.1038/ncomms9996 pubmed: 26639346 pmcid: 26639346
Nishimura, T. Developmental changes in the shape of the supralaryngeal vocal tract in Chimpanzees. Am. J. Phys. Anthropol. 126, 193–204 (2005).
Horvath, S. et al. The cerebellum ages slowly according to the epigenetic clock. Aging 7, 294–306 (2015).
doi: 10.18632/aging.100742 pubmed: 26000617 pmcid: 26000617
Kulis, M. et al. Whole-genome fingerprint of the DNA methylome during human B cell differentiation. Nat. Genet. 47, 746–756 (2015).
doi: 10.1038/ng.3291 pubmed: 26053498 pmcid: 26053498
Marco-Sola, S., Sammeth, M., Guigó, R. & Ribeca, P. The GEM mapper: fast, accurate and versatile alignment by filtration. Nat. Methods 9, 1185–1188 (2012).
doi: 10.1038/nmeth.2221 pubmed: 23103880 pmcid: 23103880
Hansen, K. D., Langmead, B. & Irizarry, R. A. BSmooth: from whole genome bisulfite sequencing reads to differentially methylated regions. Genome Biol. 13, R83 (2012).
Dabney, J. et al. Complete mitochondrial genome sequence of a Middle Pleistocene cave bear reconstructed from ultrashort DNA fragments. Proc. Natl Acad. Sci. USA 110, 15758–15763 (2013).
doi: 10.1073/pnas.1314445110 pubmed: 24019490 pmcid: 24019490
Rohland, N. & Hofreiter, M. Ancient DNA extraction from bones and teeth. Nat. Protoc. 2, 1756–1762 (2007).
doi: 10.1038/nprot.2007.247 pubmed: 17641642 pmcid: 17641642
Boyle, P. et al. Gel-free multiplexed reduced representation bisulfite sequencing for large-scale DNA methylation profiling. Genome Biol. 13, R92 (2012).
doi: 10.1186/gb-2012-13-10-r92 pubmed: 23034176 pmcid: 23034176
Barnett, R. & Larson, G. A phenol-chloroform protocol for extracting DNA from ancient samples. Methods Mol. Biol. 840, 13–19 (2012).
doi: 10.1007/978-1-61779-516-9_2 pubmed: 22237516 pmcid: 22237516
Fortin, J. P., Triche, T. J. & Hansen, K. D. Preprocessing, normalization and integration of the Illumina HumanMethylationEPIC array with minfi. Bioinformatics 33, 558–560 (2017).
Hernando-Herraez, I. et al. Dynamics of DNA methylation in recent human and great ape evolution. PLoS Genet. 9, e1003763 (2013).
doi: 10.1371/journal.pgen.1003763 pubmed: 24039605 pmcid: 24039605
Sirak, K. A. et al. A minimally-invasive method for sampling human petrous bones from the cranial base for ancient DNA analysis. Biotechniques 62, 283–289 (2017).
doi: 10.2144/000114558 pubmed: 28625158 pmcid: 28625158
Hanghøj, K. et al. Fast, accurate and automatic ancient nucleosome and methylation maps with epiPALEOMIX. Mol. Biol. Evol. 33, 3284–3298 (2016).
Blasi, D. E. et al. Human sound systems are shaped by post-Neolithic changes in bite configuration. Science 363, eaav3218 (2019).
Guo, M. et al. Epigenetic profiling of growth plate chondrocytes sheds insight into regulatory genetic variation influencing height. elife 6, e29329 (2017).
Bagheri-Fam, S. et al. Long-range upstream and downstream enhancers control distinct subsets of the complex spatiotemporal Sox9 expression pattern. Dev. Biol. 291, 382–397 (2006).
doi: 10.1016/j.ydbio.2005.11.013 pubmed: 16458883 pmcid: 16458883
Sekido, R. & Lovell-Badge, R. Sex determination involves synergistic action of SRY and SF1 on a specific Sox9 enhancer. Nature 453, 930–934 (2008).
doi: 10.1038/nature06944 pubmed: 18454134 pmcid: 18454134
Varanasi, S. S. et al. Skeletal site-related variation in human trabecular bone transcriptome and signaling. PLoS ONE 5, e10692 (2010).

Auteurs

David Gokhman (D)

Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel. david.gokhman@mail.huji.ac.il.

Malka Nissim-Rafinia (M)

Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel.

Lily Agranat-Tamir (L)

Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel.
Department of Statistics, The Hebrew University of Jerusalem, 91905, Jerusalem, Israel.

Genevieve Housman (G)

School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, 85281, USA.
Center for Evolution and Medicine, Arizona State University, Tempe, AZ, 85287, USA.
ORCID: 0000-0002-3482-7511

Raquel García-Pérez (R)

Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003, Barcelona, Spain.

Esther Lizano (E)

Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003, Barcelona, Spain.
ORCID: 0000-0003-3304-9807

Olivia Cheronet (O)

Department of Evolutionary Anthropology, University of Vienna, 1090, Vienna, Austria.
ORCID: 0000-0001-6760-1204

Swapan Mallick (S)

Broad Institute, Cambridge, MA, 02138, USA.
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, 02115, USA.

Maria A Nieves-Colón (MA)

School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, 85281, USA.
Center for Evolution and Medicine, Arizona State University, Tempe, AZ, 85287, USA.

Heng Li (H)

Broad Institute, Cambridge, MA, 02138, USA.

Songül Alpaslan-Roodenberg (S)

Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.

Mario Novak (M)

Institute for Anthropological Research, 10000, Zagreb, Croatia.
Earth Institute and School of Archaeology, University College Dublin, Dublin 4, Ireland.

Hongcang Gu (H)

Broad Institute, Cambridge, MA, 02138, USA.

Jason M Osinski (JM)

Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14203, USA.

Manuel Ferrando-Bernal (M)

Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003, Barcelona, Spain.

Pere Gelabert (P)

Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003, Barcelona, Spain.
ORCID: 0000-0003-3019-0725

Iddi Lipende (I)

Gombe Stream Research Center, Jane Goodall Institute, Kigoma, Tanzania.

Deus Mjungu (D)

Gombe Stream Research Center, Jane Goodall Institute, Kigoma, Tanzania.

Ivanela Kondova (I)

Biomedical Primate Research Centre (BPRC), Rijswijk, Netherlands.
ORCID: 0000-0003-2745-6094

Ronald Bontrop (R)

Biomedical Primate Research Centre (BPRC), Rijswijk, Netherlands.
ORCID: 0000-0003-0874-6467

Ottmar Kullmer (O)

Department of Palaeoanthropology and Messel Research, Senckenberg Center of Human Evolution and Paleoecology, Frankfurt am Main, Germany.
ORCID: 0000-0002-5929-8070

Gerhard Weber (G)

Department of Evolutionary Anthropology, University of Vienna, 1090, Vienna, Austria.

Tal Shahar (T)

Department of Neurosurgery, Shaare Zedek Medical Center, Jerusalem, Israel.

Mona Dvir-Ginzberg (M)

Laboratory of Cartilage Biology, Institute of Dental Sciences, Faculty of Dental Medicine, Hebrew University of Jerusalem, 91120, Jerusalem, Israel.
ORCID: 0000-0003-3089-6875

Marina Faerman (M)

Laboratory of Bioanthropology and Ancient DNA, Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem, 91120, Jerusalem, Israel.

Ellen E Quillen (EE)

Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, 85287, USA.

Alexander Meissner (A)

Broad Institute, Cambridge, MA, 02138, USA.
Harvard Stem Cell Institute, Cambridge, MA, 02138, USA.
Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA, 02138, USA.
ORCID: 0000-0001-8646-7469

Yonatan Lahav (Y)

Otolaryngology - Head & Neck Surgery Department, Laryngeal Surgery Unit, Kaplan Medical Center, Rehovot, Israel.
The Hebrew University Medical School, Jerusalem, Israel.

Leonid Kandel (L)

Orthopaedic Department, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.

Meir Liebergall (M)

Orthopaedic Department, Hadassah - Hebrew University Medical Center, Jerusalem, Israel.

María E Prada (ME)

I.E.S.O. 'Los Salados'. Junta de Castilla y León, León, Spain.

Julio M Vidal (JM)

Junta de Castilla y León, Servicio de Cultura de León, León, Spain.
ORCID: 0000-0002-5309-0586

Richard M Gronostajski (RM)

Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14203, USA.
Genetics, Genomics and Bioinformatics Program, New York State Center of Excellence in Bioinformatics and Life Sciences, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, 14203, USA.
ORCID: 0000-0003-4264-208X

Anne C Stone (AC)

School of Human Evolution and Social Change, Arizona State University, Tempe, AZ, 85281, USA.
Center for Evolution and Medicine, Arizona State University, Tempe, AZ, 85287, USA.
Institute of Human Origins, Arizona State University, Tempe, AZ, 85287, USA.
ORCID: 0000-0001-8021-8314

Benjamin Yakir (B)

Department of Statistics, The Hebrew University of Jerusalem, 91905, Jerusalem, Israel.

Carles Lalueza-Fox (C)

Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003, Barcelona, Spain.
ORCID: 0000-0002-1730-5914

Ron Pinhasi (R)

Department of Evolutionary Anthropology, University of Vienna, 1090, Vienna, Austria.
ORCID: 0000-0003-1629-8131

David Reich (D)

Broad Institute, Cambridge, MA, 02138, USA.
Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA.
Howard Hughes Medical Institute, Harvard Medical School, Boston, MA, 02115, USA.
ORCID: 0000-0002-7037-5292

Tomas Marques-Bonet (T)

Institute of Evolutionary Biology (UPF-CSIC), PRBB, 08003, Barcelona, Spain.
Catalan Institution of Research and Advanced Studies (ICREA), 08010, Barcelona, Spain.
CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), 08028, Barcelona, Spain.
Institut Català de Paleontologia Miquel Crusafont, Universitat Autònoma de Barcelona, Edifici ICTA-ICP, c/ Columnes s/n, Barcelona, Spain.
ORCID: 0000-0002-5597-3075

Eran Meshorer (E)

Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel. eran.meshorer@mail.huji.ac.il.
The Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University of Jerusalem, 91904, Jerusalem, Israel. eran.meshorer@mail.huji.ac.il.
ORCID: 0000-0003-4777-986X

Liran Carmel (L)

Department of Genetics, The Alexander Silberman Institute of Life Sciences, Faculty of Science, The Hebrew University of Jerusalem, 91904, Jerusalem, Israel. liran.carmel@huji.ac.il.
ORCID: 0000-0003-0225-8550

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1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Differential DNA methylation of vocal and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Differential DNA methylation of vocal and...
questionsmedicales.fr › Eucaryotes › Animaux › Differential DNA methylation of vocal and...
questionsmedicales.fr › Cellules › Cellules cultivées › Differential DNA methylation of vocal and...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › Differential DNA methylation of vocal and...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Chondrocytes › Differential DNA methylation of vocal and...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › Differential DNA methylation of vocal and...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › ADN ancien › Differential DNA methylation of vocal and...
questionsmedicales.fr › Phénomènes biologiques › Évolution biologique › Évolution moléculaire › Differential DNA methylation of vocal and...
questionsmedicales.fr › Régions du corps › Tête › Face › Differential DNA methylation of vocal and...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Séquences d'acides nucléiques régulatrices › Réseaux de régulation génique › Differential DNA methylation of vocal and...
questionsmedicales.fr › Phénomènes biologiques › Évolution biologique › Spéciation génétique › Differential DNA methylation of vocal and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Differential DNA methylation of vocal and...
questionsmedicales.fr › Appareil respiratoire › Larynx › Differential DNA methylation of vocal and...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Differential DNA methylation of vocal and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Néandertaliens › Differential DNA methylation of vocal and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Pan troglodytes › Differential DNA methylation of vocal and...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Differential DNA methylation of vocal and...
questionsmedicales.fr › Phénomènes physiologiques respiratoires et circulatoires › Phénomènes physiologiques respiratoires › Phonation › Differential DNA methylation of vocal and...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › Differential DNA methylation of vocal and...
questionsmedicales.fr › Système stomatognathique › Bouche › Langue › Differential DNA methylation of vocal and...
questionsmedicales.fr › Appareil respiratoire › Larynx › Glotte › Plis vocaux › Differential DNA methylation of vocal and...
questionsmedicales.fr › Comportement et mécanismes comportementaux › Comportement › Comportement animal › Communication animale › Vocalisation animale › Differential DNA methylation of vocal and...