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

Philipp Gunz (Corresponding author)
, 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 (Corresponding author)

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1, 2, 3, 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.

Original language	English
Pages (from-to)	120-127.e5
Number of pages	13
Journal	Current Biology
Volume	29
Issue number	1
DOIs	https://doi.org/10.1016/j.cub.2018.10.065
Publication status	Published - 7 Jan 2019
Externally published	Yes

Funding

BIG is part of Cognomics, supported by the Donders-Centre for Cognitive Neuroimaging, Departments of Human-Genetics and Cognitive Neuroscience (Radboud University Medical Centre), MPI for Psycholinguistics. Additional funding: BBMRI-NL , Hersenstichting-Nederland , Netherlands Organisation for Scientific Research (NWO), FP7/2007–2013 : 602450 (IMAGEMEND) and 602805 (Aggressotype), NIH-U54-EB020403 . SHIP funded by BMBF Germany ( 01ZZ9603 , 01ZZ0103 , 01ZZ0403 , 03IS2061A , 03ZIK012 ), Federal State, Ministry of Cultural Affairs & Social Ministry of Mecklenburg-West Pomerania, Siemens Healthineers. Thanks to InterSystems (Caché-Campus), German Research Foundation ( GR-1912/5-1 ), Max Planck Society , Nomis Foundation (to S.P.), and NIH 1-U24-RR021992 and 1-U24-RR025736-01 . Funding sources had no role in study design, data collection, analysis, and interpretation. We thank the anonymous referees for detailed and constructive feedback that helped improve the manuscript.

Austrian Fields of Science 2012

106056 Biological anthropology

Keywords

basal ganglia
brain shape
cerebellum
evolution
gene expression
genetic association
homo sapiens
magnetic resonance imaging
myelination
Neandertal
MYELINATION
BASAL GANGLIA
HOMO
SCHIZOPHRENIA
AKT
GENOME
EVOLUTION
SEQUENCE
ASSOCIATION
PHLPP

Access to Document

10.1016/j.cub.2018.10.065Licence: CC BY-NC-ND 4.0

Cite this

Gunz, P., Tilot, A. K., Wittfeld, K., Teumer, A., Shapland, C. Y., van Erp, T. G. M., Dannemann, M., Vernot, B., Neubauer, S., Guadalupe, T., Fernández, G., Brunner, H. G., Enard, W., Fallon, J., Hosten, N., Völker, U., Profico, A., Di Vincenzo, F., Manzi, G., ... Fisher, S. E. (2019). Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity. Current Biology, 29(1), 120-127.e5. https://doi.org/10.1016/j.cub.2018.10.065

@article{bf12b99b801c479690e41e04322b21ac,

title = "Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity",

abstract = "One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1, 2, 3, 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 = "basal ganglia, brain shape, cerebellum, evolution, gene expression, genetic association, homo sapiens, magnetic resonance imaging, myelination, Neandertal, MYELINATION, BASAL GANGLIA, HOMO, SCHIZOPHRENIA, AKT, GENOME, EVOLUTION, SEQUENCE, ASSOCIATION, PHLPP",

author = "Philipp Gunz and Tilot, \{Amanda K.\} and Katharina Wittfeld and Alexander Teumer and Shapland, \{Chin Yang\} and \{van Erp\}, \{Theo G.M.\} and Michael Dannemann and Benjamin Vernot and Simon Neubauer and Tulio Guadalupe and Guill{\'e}n Fern{\'a}ndez and Brunner, \{Han G.\} and Wolfgang Enard and James Fallon and Norbert Hosten and Uwe V{\"o}lker and Antonio Profico and \{Di Vincenzo\}, Fabio and Giorgio Manzi and Janet Kelso and \{St. Pourcain\}, Beate and Hublin, \{Jean Jacques\} and Barbara Franke and Svante P{\"a}{\"a}bo and Fabio Macciardi and Grabe, \{Hans J.\} and Fisher, \{Simon E.\}",

note = "Publisher Copyright: {\textcopyright} 2018 The Authors",

year = "2019",

month = jan,

day = "7",

doi = "10.1016/j.cub.2018.10.065",

language = "English",

volume = "29",

pages = "120--127.e5",

journal = "Current Biology",

issn = "0960-9822",

publisher = "CELL PRESS",

number = "1",

}

Gunz, P, Tilot, AK, Wittfeld, K, Teumer, A, Shapland, CY, van Erp, TGM, Dannemann, M, Vernot, B, Neubauer, S, Guadalupe, T, Fernández, G, Brunner, HG, Enard, W, Fallon, J, Hosten, N, Völker, U, Profico, A, Di Vincenzo, F, Manzi, G, Kelso, J, St. Pourcain, B, Hublin, JJ, Franke, B, Pääbo, S, Macciardi, F, Grabe, HJ & Fisher, SE 2019, 'Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity', Current Biology, vol. 29, no. 1, pp. 120-127.e5. https://doi.org/10.1016/j.cub.2018.10.065

TY - JOUR

T1 - Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity

AU - Gunz, Philipp

AU - Tilot, Amanda K.

AU - Wittfeld, Katharina

AU - Teumer, Alexander

AU - Shapland, Chin Yang

AU - van Erp, Theo G.M.

AU - Dannemann, Michael

AU - Vernot, Benjamin

AU - Neubauer, Simon

AU - Guadalupe, Tulio

AU - Fernández, Guillén

AU - Brunner, Han G.

AU - Enard, Wolfgang

AU - Fallon, James

AU - Hosten, Norbert

AU - Völker, Uwe

AU - Profico, Antonio

AU - Di Vincenzo, Fabio

AU - Manzi, Giorgio

AU - Kelso, Janet

AU - St. Pourcain, Beate

AU - Hublin, Jean Jacques

AU - Franke, Barbara

AU - Pääbo, Svante

AU - Macciardi, Fabio

AU - Grabe, Hans J.

AU - Fisher, Simon E.

PY - 2019/1/7

Y1 - 2019/1/7

N2 - One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1, 2, 3, 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.

AB - One of the features that distinguishes modern humans from our extinct relatives and ancestors is a globular shape of the braincase [1, 2, 3, 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.

KW - basal ganglia

KW - brain shape

KW - cerebellum

KW - evolution

KW - gene expression

KW - genetic association

KW - homo sapiens

KW - magnetic resonance imaging

KW - myelination

KW - Neandertal

KW - MYELINATION

KW - BASAL GANGLIA

KW - HOMO

KW - SCHIZOPHRENIA

KW - AKT

KW - GENOME

KW - EVOLUTION

KW - SEQUENCE

KW - ASSOCIATION

KW - PHLPP

UR - https://www.scopus.com/pages/publications/85059620511

U2 - 10.1016/j.cub.2018.10.065

DO - 10.1016/j.cub.2018.10.065

M3 - Article

C2 - 30554901

AN - SCOPUS:85059620511

SN - 0960-9822

VL - 29

SP - 120-127.e5

JO - Current Biology

JF - Current Biology

IS - 1

ER -

Neandertal Introgression Sheds Light on Modern Human Endocranial Globularity

Abstract

Funding

Austrian Fields of Science 2012

Keywords

Access to Document

Other files and links

Fingerprint

Cite this