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

Nature volume 418, pages 869872 (22 August 2002) | Download Citation

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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.

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References

  1. 1.

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

  2. 2.

    , , , & A forkhead-domain gene is mutated in a severe speech and language disorder. Nature 413, 519–523 (2001)

  3. 3.

    , , , & Localisation of a gene implicated in a severe speech and language disorder. Nature Genet. 18, 168–170 (1998)

  4. 4.

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

  5. 5.

    & 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)

  6. 6.

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

  7. 7.

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

  8. 8.

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

  9. 9.

    & A molecular timescale for vertebrate evolution. Nature 392, 917–920 (1998)

  10. 10.

    , & Molecular dating and biogeography of the early placental mammal radiation. J. Hered. 92, 212–219 (2001)

  11. 11.

    & 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)

  12. 12.

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

  13. 13.

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

  14. 14.

    , & Properties of statistical tests of neutrality for DNA polymorphism data. Genetics 141, 413–429 (1995)

  15. 15.

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

  16. 16.

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

  17. 17.

    & Hitchhiking under positive darwinian selection. Genetics 155, 1405–1413 (2000)

  18. 18.

    , , , & 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)

  19. 19.

    & Familial aggregation of a developmental language disorder. Cognition 39, 1–50 (1991)

  20. 20.

    , & Behavioural analysis of an inherited speech and language disorder: Comparison with acquired aphasia. Brain 125, 452–464 (2002)

  21. 21.

    & When did the human population size start increasing? Genetics 155, 1865–1874 (2000)

  22. 22.

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

  23. 23.

    , & 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)

  24. 24.

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

  25. 25.

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

  26. 26.

    , & The prosite database, its status in 1997. Nucleic Acids Res. 25, 217–221 (1997)

  27. 27.

    , & Patterns of genetic variation at a chromosome 4 locus of Drosophila melanogaster and D. simulans. Genetics 160, 493–507 (2002)

  28. 28.

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

  29. 29.

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

  30. 30.

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

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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.

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  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, Oxford OX3 7BN, UK

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

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The authors declare that they have no competing financial interests.

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Correspondence to Svante Pääbo.

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https://doi.org/10.1038/nature01025

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