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


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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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.

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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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Correspondence to Svante Pääbo.

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Supplementary information


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)


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)


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)

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

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