Skip to main content
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian
  • Log in
  • My Cart

Main menu

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home

Advanced Search

  • Home
  • Articles
    • Current
    • Latest Articles
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • Archive
  • Front Matter
  • News
    • For the Press
    • Highlights from Latest Articles
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Purpose and Scope
    • Editorial and Journal Policies
    • Submission Procedures
    • For Reviewers
    • Author FAQ

New Research In

Physical Sciences

Featured Portals

  • Physics
  • Chemistry
  • Sustainability Science

Articles by Topic

  • Applied Mathematics
  • Applied Physical Sciences
  • Astronomy
  • Computer Sciences
  • Earth, Atmospheric, and Planetary Sciences
  • Engineering
  • Environmental Sciences
  • Mathematics
  • Statistics

Social Sciences

Featured Portals

  • Anthropology
  • Sustainability Science

Articles by Topic

  • Economic Sciences
  • Environmental Sciences
  • Political Sciences
  • Psychological and Cognitive Sciences
  • Social Sciences

Biological Sciences

Featured Portals

  • Sustainability Science

Articles by Topic

  • Agricultural Sciences
  • Anthropology
  • Applied Biological Sciences
  • Biochemistry
  • Biophysics and Computational Biology
  • Cell Biology
  • Developmental Biology
  • Ecology
  • Environmental Sciences
  • Evolution
  • Genetics
  • Immunology and Inflammation
  • Medical Sciences
  • Microbiology
  • Neuroscience
  • Pharmacology
  • Physiology
  • Plant Biology
  • Population Biology
  • Psychological and Cognitive Sciences
  • Sustainability Science
  • Systems Biology

Patterns of coding variation in the complete exomes of three Neandertals

Sergi Castellano, Genís Parra, Federico A. Sánchez-Quinto, Fernando Racimo, Martin Kuhlwilm, Martin Kircher, Susanna Sawyer, Qiaomei Fu, Anja Heinze, Birgit Nickel, Jesse Dabney, Michael Siebauer, Louise White, Hernán A. Burbano, Gabriel Renaud, Udo Stenzel, Carles Lalueza-Fox, Marco de la Rasilla, Antonio Rosas, Pavao Rudan, Dejana Brajković, Željko Kucan, Ivan Gušic, Michael V. Shunkov, Anatoli P. Derevianko, Bence Viola, Matthias Meyer, Janet Kelso, Aida M. Andrés, and Svante Pääbo
PNAS May 6, 2014 111 (18) 6666-6671; published ahead of print April 21, 2014 https://doi.org/10.1073/pnas.1405138111
Sergi Castellano
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: sergi.castellano@eva.mpg.depaabo@eva.mpg.de
Genís Parra
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Federico A. Sánchez-Quinto
bInstitute of Evolutionary Biology, Consejo Superior de Investigaciones Científicas, Universitat Pompeu Fabra, 08003 Barcelona, Spain;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fernando Racimo
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;cDepartment of Integrative Biology, University of California, Berkeley, CA 94720;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin Kuhlwilm
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin Kircher
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;dDepartment of Genome Sciences, University of Washington, Seattle, WA 98195;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susanna Sawyer
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qiaomei Fu
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;eKey Laboratory of Vertebrate Evolution and Human Origins of the Chinese Academy of Sciences, Institute of Vertebrate Palaeontology and Palaeoanthropology, Chinese Academy of Sciences, Beijing 100044, China;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anja Heinze
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Birgit Nickel
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jesse Dabney
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Siebauer
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Louise White
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hernán A. Burbano
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;fDepartment of Molecular Biology, Max Planck Institute for Developmental Biology, 72076 Tuebingen, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gabriel Renaud
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Udo Stenzel
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carles Lalueza-Fox
bInstitute of Evolutionary Biology, Consejo Superior de Investigaciones Científicas, Universitat Pompeu Fabra, 08003 Barcelona, Spain;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marco de la Rasilla
gÁrea de Prehistoria, Departamento de Historia, Universidad de Oviedo, 33011 Oviedo, Spain;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Antonio Rosas
hDepartamento de Paleobiología, Museo Nacional de Ciencias Naturales, Consejo Superior de Investigaciones Científicas, 28006 Madrid, Spain;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pavao Rudan
iAnthropology Center of the Croatian Academy of Sciences and Arts, HR-10000 Zagreb, Croatia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dejana Brajković
jCroatian Academy of Sciences and Arts, Institute for Quaternary Paleontology and Geology, HR-10000 Zagreb, Croatia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Željko Kucan
iAnthropology Center of the Croatian Academy of Sciences and Arts, HR-10000 Zagreb, Croatia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ivan Gušic
jCroatian Academy of Sciences and Arts, Institute for Quaternary Paleontology and Geology, HR-10000 Zagreb, Croatia;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael V. Shunkov
kPaleolithic Department, Institute of Archeology and Ethnography, Russian Academy of Sciences, Siberian Branch, Novosibirsk 630090, Russia; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anatoli P. Derevianko
kPaleolithic Department, Institute of Archeology and Ethnography, Russian Academy of Sciences, Siberian Branch, Novosibirsk 630090, Russia; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bence Viola
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;lDepartment of Human Evolution, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthias Meyer
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Janet Kelso
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Aida M. Andrés
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Svante Pääbo
aDepartment of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, 04103 Leipzig, Germany;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: sergi.castellano@eva.mpg.depaabo@eva.mpg.de
  1. Contributed by Svante Pääbo, March 21, 2014 (sent for review January 17, 2014)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

We use a hybridization approach to enrich the DNA from the protein-coding fraction of the genomes of two Neandertal individuals from Spain and Croatia. By analyzing these two exomes together with the genome sequence of a Neandertal from Siberia we show that the genetic diversity of Neandertals was lower than that of present-day humans and that the pattern of coding variation suggests that Neandertal populations were small and isolated from one another. We also show that genes involved in skeletal morphology have changed more than expected on the Neandertal evolutionary lineage whereas genes involved in pigmentation and behavior have changed more on the modern human lineage.

Abstract

We present the DNA sequence of 17,367 protein-coding genes in two Neandertals from Spain and Croatia and analyze them together with the genome sequence recently determined from a Neandertal from southern Siberia. Comparisons with present-day humans from Africa, Europe, and Asia reveal that genetic diversity among Neandertals was remarkably low, and that they carried a higher proportion of amino acid-changing (nonsynonymous) alleles inferred to alter protein structure or function than present-day humans. Thus, Neandertals across Eurasia had a smaller long-term effective population than present-day humans. We also identify amino acid substitutions in Neandertals and present-day humans that may underlie phenotypic differences between the two groups. We find that genes involved in skeletal morphology have changed more in the lineage leading to Neandertals than in the ancestral lineage common to archaic and modern humans, whereas genes involved in behavior and pigmentation have changed more on the modern human lineage.

  • ancient DNA
  • exome capture
  • site frequency spectra
  • paleogenetics

Footnotes

  • ↵1To whom correspondence may be addressed. E-mail: sergi.castellano{at}eva.mpg.de or paabo{at}eva.mpg.de.
  • ↵2G.P., F.A.S.-Q., F.R., and M. Kuhlwilm contributed equally to this work.

  • Author contributions: S.C., F.R., M.M., J.K., A.M.A., and S.P. designed research; S.C., G.P., F.A.S.-Q., F.R., M. Kuhlwilm, S.S., Q.F., A.H., B.N., J.D., L.W., B.V., M.M., and A.M.A. performed research; S.S., Q.F., A.H., B.N., J.D., H.A.B., C.L.-F., M.d.l.R., A.R., P.R., D.B., Z.K., I.G., M.V.S., A.P.D., and M.M. contributed new reagents/analytic tools; S.C., G.P., F.A.S.-Q., F.R., M. Kuhlwilm, M. Kircher, M.S., G.R., and U.S. analyzed data; and S.C., F.A.S.-Q., F.R., B.V., J.K., A.M.A., and S.P. wrote the paper.

  • The authors declare no conflict of interest.

  • Data deposition: The exome sequence capture data reported in this paper have been deposited in the European Nucleotide Archive (accession no. ERP002457). These data are also available at http://cdna.eva.mpg.de/neandertal/exomes/.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1405138111/-/DCSupplemental.

View Full Text
PreviousNext
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Patterns of coding variation in the complete exomes of three Neandertals
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
Citation Tools
Patterns of coding variation in Neandertal exomes
Sergi Castellano, Genís Parra, Federico A. Sánchez-Quinto, Fernando Racimo, Martin Kuhlwilm, Martin Kircher, Susanna Sawyer, Qiaomei Fu, Anja Heinze, Birgit Nickel, Jesse Dabney, Michael Siebauer, Louise White, Hernán A. Burbano, Gabriel Renaud, Udo Stenzel, Carles Lalueza-Fox, Marco de la Rasilla, Antonio Rosas, Pavao Rudan, Dejana Brajković, Željko Kucan, Ivan Gušic, Michael V. Shunkov, Anatoli P. Derevianko, Bence Viola, Matthias Meyer, Janet Kelso, Aida M. Andrés, Svante Pääbo
Proceedings of the National Academy of Sciences May 2014, 111 (18) 6666-6671; DOI: 10.1073/pnas.1405138111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Patterns of coding variation in Neandertal exomes
Sergi Castellano, Genís Parra, Federico A. Sánchez-Quinto, Fernando Racimo, Martin Kuhlwilm, Martin Kircher, Susanna Sawyer, Qiaomei Fu, Anja Heinze, Birgit Nickel, Jesse Dabney, Michael Siebauer, Louise White, Hernán A. Burbano, Gabriel Renaud, Udo Stenzel, Carles Lalueza-Fox, Marco de la Rasilla, Antonio Rosas, Pavao Rudan, Dejana Brajković, Željko Kucan, Ivan Gušic, Michael V. Shunkov, Anatoli P. Derevianko, Bence Viola, Matthias Meyer, Janet Kelso, Aida M. Andrés, Svante Pääbo
Proceedings of the National Academy of Sciences May 2014, 111 (18) 6666-6671; DOI: 10.1073/pnas.1405138111
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 116 (7)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
    • Abstract
    • Results and Discussion
    • Methods
    • Acknowledgments
    • Footnotes
    • References
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Several aspects of the proposal, which aims to expand open access, require serious discussion and, in some cases, a rethink.
Opinion: “Plan S” falls short for society publishers—and for the researchers they serve
Several aspects of the proposal, which aims to expand open access, require serious discussion and, in some cases, a rethink.
Image credit: Dave Cutler (artist).
Several large or long-lived animals seem strangely resistant to developing cancer. Elucidating the reasons why could lead to promising cancer-fighting strategies in humans.
Core Concept: Solving Peto’s Paradox to better understand cancer
Several large or long-lived animals seem strangely resistant to developing cancer. Elucidating the reasons why could lead to promising cancer-fighting strategies in humans.
Image credit: Shutterstock.com/ronnybas frimages.
Featured Profile
PNAS Profile of NAS member and biochemist Hao Wu
 Nonmonogamous strawberry poison frog (Oophaga pumilio).  Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Putative signature of monogamy
A study suggests a putative gene-expression hallmark common to monogamous male vertebrates of some species, namely cichlid fishes, dendrobatid frogs, passeroid songbirds, common voles, and deer mice, and identifies 24 candidate genes potentially associated with monogamy.
Image courtesy of Yusan Yang (University of Pittsburgh, Pittsburgh).
Active lifestyles. Image courtesy of Pixabay/MabelAmber.
Meaningful life tied to healthy aging
Physical and social well-being in old age are linked to self-assessments of life worth, and a spectrum of behavioral, economic, health, and social variables may influence whether aging individuals believe they are leading meaningful lives.
Image courtesy of Pixabay/MabelAmber.

More Articles of This Classification

Biological Sciences

  • Structural basis for activity of TRIC counter-ion channels in calcium release
  • PGC1A regulates the IRS1:IRS2 ratio during fasting to influence hepatic metabolism downstream of insulin
  • Altered neural odometry in the vertical dimension
Show more

Evolution

  • Molecular mechanism and history of non-sense to sense evolution of antifreeze glycoprotein gene in northern gadids
  • Transitions between foot postures are associated with elevated rates of body size evolution in mammals
  • Hagfish from the Cretaceous Tethys Sea and a reconciliation of the morphological–molecular conflict in early vertebrate phylogeny
Show more

Related Content

  • No related articles found.
  • Scopus
  • PubMed
  • Google Scholar

Cited by...

  • Testing for ancient selection using cross-population allele frequency differentiation
  • Neanderthal Genomics Suggests a Pleistocene Time Frame for the First Epidemiologic Transition
  • An abundance of developmental anomalies and abnormalities in Pleistocene people
  • The evolution of modern human brain shape
  • A high-coverage Neandertal genome from Vindija Cave in Croatia
  • Early history of Neanderthals and Denisovans
  • Neanderthals and Denisovans as biological invaders
  • Joint Estimation of Relatedness Coefficients and Allele Frequencies from Ancient Samples
  • Neandertal and Denisovan DNA from Pleistocene sediments
  • A Temporal Perspective on the Interplay of Demography and Selection on Deleterious Variation in Humans
  • Morphology and function of Neandertal and modern human ear ossicles
  • Palaeoproteomic evidence identifies archaic hominins associated with the Chatelperronian at the Grotte du Renne
  • Ancient DNA and human history
  • The Genetic Cost of Neanderthal Introgression
  • Testing for Ancient Selection Using Cross-population Allele Frequency Differentiation
  • Common variants spanning PLK4 are associated with mitotic-origin aneuploidy in human embryos
  • How to build a Neandertal
  • Scopus (99)
  • Google Scholar

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Latest Articles
  • Archive

PNAS Portals

  • Classics
  • Front Matter
  • Teaching Resources
  • Anthropology
  • Chemistry
  • Physics
  • Sustainability Science

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Press
  • Site Map

Feedback    Privacy/Legal

Copyright © 2019 National Academy of Sciences. Online ISSN 1091-6490