title: A recent evolutionary change affects a regulatory element in the human FOXP2 gene.
abstract: The FOXP2 gene is required for normal development of speech and language. By isolating and sequencing FOXP2 genomic DNA fragments from a 49,000-year-old Iberian Neandertal and 50 present-day humans, we have identified substitutions in the gene shared by all or nearly all present-day humans but absent or polymorphic in Neandertals. One such substitution is localized in intron 8 and affects a binding site for the transcription factor POU3F2, which is highly conserved among vertebrates. We find that the derived allele of this site is less efficient than the ancestral allele in activating transcription from a reporter construct. The derived allele also binds less POU3F2 dimers than POU3F2 monomers compared with the ancestral allele. Because the substitution in the POU3F2 binding site is likely to alter the regulation of FOXP2 expression, and because it is localized in a region of the gene associated with a previously described signal of positive selection, it is a plausible candidate for having caused a recent selective sweep in the FOXP2 gene.
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany. tomislav_maricic@eva.mpg.de
authors.forename: Tomislav
authors.initials: T
authors.lastname: Maricic
authors.forename: Viola
authors.initials: V
authors.lastname: Günther
authors.forename: Oleg
authors.initials: O
authors.lastname: Georgiev
authors.forename: Sabine
authors.initials: S
authors.lastname: Gehre
authors.forename: Marija
authors.initials: M
authors.lastname: Curlin
authors.forename: Christiane
authors.initials: C
authors.lastname: Schreiweis
authors.forename: Ronald
authors.initials: R
authors.lastname: Naumann
authors.forename: Hernán A
authors.initials: HA
authors.lastname: Burbano
authors.forename: Matthias
authors.initials: M
authors.lastname: Meyer
authors.forename: Carles
authors.initials: C
authors.lastname: Lalueza-Fox
authors.forename: Marco
authors.initials: M
authors.lastname: de la Rasilla
authors.forename: Antonio
authors.initials: A
authors.lastname: Rosas
authors.forename: Srecko
authors.initials: S
authors.lastname: Gajovic
authors.forename: Janet
authors.initials: J
authors.lastname: Kelso
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Enard
authors.forename: Walter
authors.initials: W
authors.lastname: Schaffner
authors.forename: Svante
authors.initials: S
authors.lastname: Pääbo
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D005787:Gene Frequency; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D059125:Neanderthals / Q000235:genetics; D050809:POU Domain Factors / Q000737:chemistry / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D017422:Sequence Analysis, DNA; D015533:Transcriptional Activation
chemical_list: C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D050809:POU Domain Factors; C085076:transcription factor Brn-2