title: Evolution of candidate transcriptional regulatory motifs since the human-chimpanzee divergence.
abstract: BACKGROUND
  Despite the recent completion of the chimpanzee genome project, few functionally significant sequence differences between humans and chimpanzees have thus far been identified. Alteration in transcriptional regulatory mechanisms represents an important platform for evolutionary change, suggesting that a significant proportion of functional human-chimpanzee sequence differences may affect regulatory elements.
  
  
  RESULTS
  To explore this hypothesis, we performed genome-wide identification of conserved candidate transcription-factor binding sites that have evolved since the divergence of humans and chimpanzees. Analysis of candidate transcription-factor binding sites conserved between mouse and chimpanzee yet absent in human indicated that loss of candidate transcription-factor binding sites in the human lineage was not random but instead correlated with the biologic functions of associated genes.
  
  
  CONCLUSIONS
  Our data support the notion that changes in transcriptional regulation have contributed to the recent evolution of humans. Moreover, genes associated with mutated candidate transcription-factor binding sites highlight potential pathways underlying human-chimpanzee divergence.
authors.affiliation: Department of Haematology, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 2XY, UK.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Donaldson
authors.forename: Berthold
authors.initials: B
authors.lastname: Göttgens
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D014644:Genetic Variation; D016678:Genome; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics*; D050436:Regulatory Elements, Transcriptional; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D014157:Transcription Factors