• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Dec 2002; 162(4): 1825–1835.
PMCID: PMC1462353

Accelerated protein evolution and origins of human-specific features: Foxp2 as an example.

Abstract

Genes responsible for human-specific phenotypes may have been under altered selective pressures in human evolution and thus exhibit changes in substitution rate and pattern at the protein sequence level. Using comparative analysis of human, chimpanzee, and mouse protein sequences, we identified two genes (PRM2 and FOXP2) with significantly enhanced evolutionary rates in the hominid lineage. PRM2 is a histone-like protein essential to spermatogenesis and was previously reported to be a likely target of sexual selection in humans and chimpanzees. FOXP2 is a transcription factor involved in speech and language development. Human FOXP2 experienced a >60-fold increase in substitution rate and incorporated two fixed amino acid changes in a broadly defined transcription suppression domain. A survey of a diverse group of placental mammals reveals the uniqueness of the human FOXP2 sequence and a population genetic analysis indicates possible adaptive selection behind the accelerated evolution. Taken together, our results suggest an important role that FOXP2 may have played in the origin of human speech and demonstrate a strategy for identifying candidate genes underlying the emergences of human-specific features.

Full Text

The Full Text of this article is available as a PDF (168K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Archibald JD, Averianov AO, Ekdale EG. Late Cretaceous relatives of rabbits, rodents, and other extant eutherian mammals. Nature. 2001 Nov 1;414(6859):62–65. [PubMed]
  • Brunet Michel, Guy Franck, Pilbeam David, Mackaye Hassane Taisso, Likius Andossa, Ahounta Djimdoumalbaye, Beauvilain Alain, Blondel Cécile, Bocherens Hervé, Boisserie Jean-Renaud, et al. A new hominid from the Upper Miocene of Chad, Central Africa. Nature. 2002 Jul 11;418(6894):145–151. [PubMed]
  • Newbury DF, Bonora E, Lamb JA, Fisher SE, Lai CSL, Baird G, Jannoun L, Slonims V, Stott CM, Merricks MJ, et al. FOXP2 is not a major susceptibility gene for autism or specific language impairment. Am J Hum Genet. 2002 May;70(5):1318–1327. [PMC free article] [PubMed]
  • Rozas J, Rozas R. DnaSP version 3: an integrated program for molecular population genetics and molecular evolution analysis. Bioinformatics. 1999 Feb;15(2):174–175. [PubMed]
  • Enard Wolfgang, Khaitovich Philipp, Klose Joachim, Zöllner Sebastian, Heissig Florian, Giavalisco Patrick, Nieselt-Struwe Kay, Muchmore Elaine, Varki Ajit, Ravid Rivka, et al. Intra- and interspecific variation in primate gene expression patterns. Science. 2002 Apr 12;296(5566):340–343. [PubMed]
  • Saitou N, Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. [PubMed]
  • Shu W, Yang H, Zhang L, Lu MM, Morrisey EE. Characterization of a new subfamily of winged-helix/forkhead (Fox) genes that are expressed in the lung and act as transcriptional repressors. J Biol Chem. 2001 Jul 20;276(29):27488–27497. [PubMed]
  • Fujiyama Asao, Watanabe Hidemi, Toyoda Atsushi, Taylor Todd D, Itoh Takehiko, Tsai Shih-Feng, Park Hong-Seog, Yaspo Marie-Laure, Lehrach Hans, Chen Zhu, et al. Construction and analysis of a human-chimpanzee comparative clone map. Science. 2002 Jan 4;295(5552):131–134. [PubMed]
  • Simonsen KL, Churchill GA, Aquadro CF. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics. 1995 Sep;141(1):413–429. [PMC free article] [PubMed]
  • Fullerton SM, Bond J, Schneider JA, Hamilton B, Harding RM, Boyce AJ, Clegg JB. Polymorphism and divergence in the beta-globin replication origin initiation region. Mol Biol Evol. 2000 Jan;17(1):179–188. [PubMed]
  • Stauffer RL, Walker A, Ryder OA, Lyons-Weiler M, Hedges SB. Human and ape molecular clocks and constraints on paleontological hypotheses. J Hered. 2001 Nov-Dec;92(6):469–474. [PubMed]
  • Gagneux P, Varki A. Genetic differences between humans and great apes. Mol Phylogenet Evol. 2001 Jan;18(1):2–13. [PubMed]
  • Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. [PMC free article] [PubMed]
  • Gibbons A. Which of our genes makes us human? Science. 1998 Sep 4;281(5382):1432–1434. [PubMed]
  • Gu X, Li WH. Higher rates of amino acid substitution in rodents than in humans. Mol Phylogenet Evol. 1992 Sep;1(3):211–214. [PubMed]
  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG. The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 1997 Dec 15;25(24):4876–4882. [PMC free article] [PubMed]
  • Hudson RR, Kreitman M, Aguadé M. A test of neutral molecular evolution based on nucleotide data. Genetics. 1987 May;116(1):153–159. [PMC free article] [PubMed]
  • Varki A. A chimpanzee genome project is a biomedical imperative. Genome Res. 2000 Aug;10(8):1065–1070. [PubMed]
  • Kaessmann H, Heissig F, von Haeseler A, Päbo S. DNA sequence variation in a non-coding region of low recombination on the human X chromosome. Nat Genet. 1999 May;22(1):78–81. [PubMed]
  • Wyckoff GJ, Wang W, Wu CI. Rapid evolution of male reproductive genes in the descent of man. Nature. 2000 Jan 20;403(6767):304–309. [PubMed]
  • Kumar S, Hedges SB. A molecular timescale for vertebrate evolution. Nature. 1998 Apr 30;392(6679):917–920. [PubMed]
  • Yu N, Zhao Z, Fu YX, Sambuughin N, Ramsay M, Jenkins T, Leskinen E, Patthy L, Jorde LB, Kuromori T, et al. Global patterns of human DNA sequence variation in a 10-kb region on chromosome 1. Mol Biol Evol. 2001 Feb;18(2):214–222. [PubMed]
  • Lai CS, Fisher SE, Hurst JA, Vargha-Khadem F, Monaco AP. A forkhead-domain gene is mutated in a severe speech and language disorder. Nature. 2001 Oct 4;413(6855):519–523. [PubMed]
  • Zhang J, Nei M. Accuracies of ancestral amino acid sequences inferred by the parsimony, likelihood, and distance methods. J Mol Evol. 1997;44 (Suppl 1):S139–S146. [PubMed]
  • Lambert DM, Ritchie PA, Millar CD, Holland B, Drummond AJ, Baroni C. Rates of evolution in ancient DNA from Adélie penguins. Science. 2002 Mar 22;295(5563):2270–2273. [PubMed]
  • Zhang J, Kumar S, Nei M. Small-sample tests of episodic adaptive evolution: a case study of primate lysozymes. Mol Biol Evol. 1997 Dec;14(12):1335–1338. [PubMed]
  • Lynch M, Conery JS. The evolutionary fate and consequences of duplicate genes. Science. 2000 Nov 10;290(5494):1151–1155. [PubMed]
  • Zhao Z, Jin L, Fu YX, Ramsay M, Jenkins T, Leskinen E, Pamilo P, Trexler M, Patthy L, Jorde LB, et al. Worldwide DNA sequence variation in a 10-kilobase noncoding region on human chromosome 22. Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11354–11358. [PMC free article] [PubMed]
  • Zietkiewicz E, Yotova V, Jarnik M, Korab-Laskowska M, Kidd KK, Modiano D, Scozzari R, Stoneking M, Tishkoff S, Batzer M, et al. Genetic structure of the ancestral population of modern humans. J Mol Evol. 1998 Aug;47(2):146–155. [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Cited in Books
    Cited in Books
    PubMed Central articles cited in books
  • Gene
    Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene
    HomoloGene links
  • MedGen
    MedGen
    Related information in MedGen
  • Nucleotide
    Nucleotide
    Published Nucleotide sequences
  • PopSet
    PopSet
    Published population set
  • Protein
    Protein
    Published protein sequences
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links