title: Evolution of a polymorphic regulatory element in interferon-gamma through transposition and mutation.
abstract: Mammalian transposable elements have intrinsic regulatory elements that can activate neighboring genes, and it is speculated that they can also carry extrinsic transactivating DNA sequences to new genomic locations. We have identified a polymorphic segment of the human interferon-gamma promoter region where two adjacent binding sites for NF-kappaB and NFAT originated from the insertion of an Alu element approximately 22-34 MYA. Both binding sites lie outside the Alu consensus sequence but within the boundaries of the insertion, suggesting that this segment of DNA was comobilized when the Alu element moved from another part of the genome. Sequence comparisons and examination of DNA-protein interactions across nine different primate species indicate that the inserted sequence contained the intact NFAT binding site, whereas the ability to bind NF-kappaB evolved through a series of mutations after the insertion. These observations are consistent with the notion that retropseudogenes can comobilize intact regulatory sequences to new locations and thereby influence the evolution of gene regulatory networks; however, the extent to which such events have shaped the evolution of gene regulation remains unknown.
authors.affiliation: Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom. University Department of Paediatrics, Oxford, United Kingdom. ackerman@fas.harvard.edu
authors.forename: Hans
authors.initials: H
authors.lastname: Ackerman
authors.forename: Irina
authors.initials: I
authors.lastname: Udalova
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hull
authors.forename: Dominic
authors.initials: D
authors.lastname: Kwiatkowski
mesh_terms: D020087:Alu Elements; D001483:Base Sequence; D001665:Binding Sites; D004251:DNA Transposable Elements / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism; D014644:Genetic Variation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004251:DNA Transposable Elements; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D014157:Transcription Factors; D007371:Interferon-gamma