Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Molecular evolution of FOXP2, a gene involved in speech and language

Nature volume 418, pages 869–872 (2002)Cite this article

Abstract

Language is a uniquely human trait likely to have been a prerequisite for the development of human culture. The ability to develop articulate speech relies on capabilities, such as fine control of the larynx and mouth1, that are absent in chimpanzees and other great apes. FOXP2 is the first gene relevant to the human ability to develop language2. A point mutation in FOXP2 co-segregates with a disorder in a family in which half of the members have severe articulation difficulties accompanied by linguistic and grammatical impairment3. This gene is disrupted by translocation in an unrelated individual who has a similar disorder. Thus, two functional copies of FOXP2 seem to be required for acquisition of normal spoken language. We sequenced the complementary DNAs that encode the FOXP2 protein in the chimpanzee, gorilla, orang-utan, rhesus macaque and mouse, and compared them with the human cDNA. We also investigated intraspecific variation of the human FOXP2 gene. Here we show that human FOXP2 contains changes in amino-acid coding and a pattern of nucleotide polymorphism, which strongly suggest that this gene has been the target of selection during recent human evolution.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Alignment of the amino-acid sequences inferred from the FOXP2 cDNA sequences.
Figure 2: Silent and replacement nucleotide substitutions mapped on a phylogeny of primates.

References

  1. Liebermann, P. The Biology and Evolution of Language (Harvard Univ. Press, Cambridge, Massachusetts, 1984)

    Google Scholar 

  2. Lai, C. S. L., Fisher, S. E., Hurst, J. A., Vargha-Khadem, F. & Monaco, A. P. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413, 519–523 (2001)

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Fisher, S. E., Vargha-Khadem, F., Watkins, K. E., Monaco, A. P. & Pembrey, M. E. Localisation of a gene implicated in a severe speech and language disorder. Nature Genet. 18, 168–170 (1998)

    Article  CAS  PubMed  Google Scholar 

  4. Newbury, D. F. et al. Foxp2 is not a major susceptibility gene for autism or specific language impairment. Am. J. Hum. Genet. 70, 1318–1327 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Makalowski, W. & Boguski, M. S. Evolutionary parameters of the transcribed mammalian genome: An analysis of 2,820 orthologous rodent and human sequences. Proc. Natl Acad. Sci. USA 95, 9407–9412 (1998)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rost, B. Phd: Predicting one-dimensional protein structure by profile-based neural networks. Methods Enzymol. 266, 525–539 (1996)

    Article  CAS  PubMed  Google Scholar 

  7. Kops, G. J. et al. Control of cell cycle exit and entry by protein kinase b-regulated forkhead transcription factors. Mol. Cell. Biol. 22, 2025–2036 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Brunet, A. et al. Akt promotes cell survival by phosphorylating and inhibiting a forkhead transcription factor. Cell 96, 857–868 (1999)

    Article  CAS  PubMed  Google Scholar 

  9. Kumar, S. & Hedges, S. B. A molecular timescale for vertebrate evolution. Nature 392, 917–920 (1998)

    Article  ADS  CAS  PubMed  Google Scholar 

  10. Eizirik, E., Murphy, W. J. & O'Brien, S. J. Molecular dating and biogeography of the early placental mammal radiation. J. Hered. 92, 212–219 (2001)

    Article  CAS  PubMed  Google Scholar 

  11. Chen, F. C. & Li, W. H. Genomic divergences between humans and other hominoids and the effective population size of the common ancestor of humans and chimpanzees. Am. J. Hum. Genet. 68, 444–456 (2001)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Yang, Z. Paml: A program package for phylogenetic analysis by maximum likelihood. Comput. Appl. Biosci. 13, 555–556 (1997)

    CAS  PubMed  Google Scholar 

  13. Przeworski, M. The signature of positive selection at randomly chosen loci. Genetics 160, 1179–1189 (2002)

    PubMed  PubMed Central  Google Scholar 

  14. Simonsen, K. L., Churchill, G. A. & Aquadro, C. F. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics 141, 413–429 (1995)

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Tajima, F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595 (1989)

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Stephens, J. C. et al. Haplotype variation and linkage disequilibrium in 313 human genes. Science 293, 489–493 (2001)

    Article  CAS  PubMed  Google Scholar 

  17. Fay, J. C. & Wu, C. I. Hitchhiking under positive darwinian selection. Genetics 155, 1405–1413 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Vargha-Khadem, F., Watkins, K., Alcock, K., Fletcher, P. & Passingham, R. Praxic and nonverbal cognitive deficits in a large family with a genetically transmitted speech and language disorder. Proc. Natl Acad. Sci. USA 92, 930–933 (1995)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  19. Gopnik, M. & Crago, M. B. Familial aggregation of a developmental language disorder. Cognition 39, 1–50 (1991)

    Article  CAS  PubMed  Google Scholar 

  20. Watkins, K. E., Dronkers, N. F. & Vargha-Khadem, F. Behavioural analysis of an inherited speech and language disorder: Comparison with acquired aphasia. Brain 125, 452–464 (2002)

    Article  CAS  PubMed  Google Scholar 

  21. Wall, J. D. & Przeworski, M. When did the human population size start increasing? Genetics 155, 1865–1874 (2000)

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Klein, G. The Human Career, Human Biological and Cultural Origins (Univ. Chicago Press, Chicago, 1989)

    Google Scholar 

  23. Thompson, J. D., Higgins, D. G. & Gibson, T. J. ClustalW: Improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22, 4673–4680 (1994)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Rozas, J. & Rozas, R. Dnasp version 3: An integrated program for molecular population genetics and molecular evolution analysis. Bioinformatics 15, 174–175 (1999)

    Article  CAS  PubMed  Google Scholar 

  25. Yang, Z. Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol. Biol. Evol. 15, 568–573 (1998)

    Article  CAS  PubMed  Google Scholar 

  26. Bairoch, A., Bucher, P. & Hofmann, K. The prosite database, its status in 1997. Nucleic Acids Res. 25, 217–221 (1997)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Jensen, M. A., Charlesworth, B. & Kreitman, M. Patterns of genetic variation at a chromosome 4 locus of Drosophila melanogaster and D. simulans. Genetics 160, 493–507 (2002)

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Tajima, F. Evolutionary relationship of DNA sequences in finite populations. Genetics 105, 437–460 (1983)

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Harpending, H. & Rogers, A. Genetic perspectives on human origins and differentiation. Annu. Rev. Genom. Hum. Genet. 1, 361–385 (2000)

    Article  CAS  Google Scholar 

  30. Watterson, G. A. On the number of segregating sites in genetical models without recombination. Theor. Popul. Biol. 7, 256–276 (1975)

    Article  MathSciNet  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank F. Heissig for help with the cDNA sequencing; A. von Haeseler, G. Weiss and S. Zöllner for help with the data analysis on an earlier version of the manuscript; J. Wickings at the Centre International de Recherches Medicales for DNA samples of central chimpanzees; and the Bundesminsterium für Bildung und Forschung, the Max Planck Society and the Wellcome Trust for financial support. M.P. was supported by a National Science Foundation postdoctoral research fellowship in bioinformatics. S.E.F. is a Royal Society Research Fellow and A.P.M. is a Wellcome Trust Principal Research Fellow.

Author information

Authors and Affiliations

  1. Max Planck Institute for Evolutionary Anthropology, Inselstrasse 22, D-04103, Leipzig, Germany

    Wolfgang Enard, Molly Przeworski, Victor Wiebe, Takashi Kitano & Svante Pääbo

  2. Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, OX3 7BN, Oxford, UK

    Simon E. Fisher, Cecilia S. L. Lai & Anthony P. Monaco

Authors
  1. Wolfgang Enard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Molly Przeworski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simon E. Fisher
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cecilia S. L. Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Victor Wiebe
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takashi Kitano
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Anthony P. Monaco
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Svante Pääbo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Svante Pääbo.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Supplementary information

41586_2002_BFnature01025_MOESM1_ESM.doc

Supplementary Information 1: Details on the likelihood ratio tests for the non-silent over the silent substitution rate using the PAML package. (DOC 26 kb)

41586_2002_BFnature01025_MOESM2_ESM.xls

Supplementary Information 2: A list of primer sequences used for sequencing the 14 kbp genomic fragment and a description of the PCR conditions. (XLS 29 kb)

Supplementary Information 3: Details on samples and sequencing procedures. (DOC 24 kb)

41586_2002_BFnature01025_MOESM4_ESM.jpg

Supplementary Information Figure 4: Figure containing sequence traces of both strands for each variable position. An example of a homozygous and a heterozygous individual is shown. (JPG 417 kb)

Supplementary Information 5: Table of the variable sites found in the forty chromosomes. (XLS 57 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Enard, W., Przeworski, M., Fisher, S. et al. Molecular evolution of FOXP2, a gene involved in speech and language. Nature 418, 869–872 (2002). https://doi.org/10.1038/nature01025

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature01025

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing