title: Lineage-specific imprinting and evolution of the zinc-finger gene ZIM2.
abstract: We have carried out an in-depth comparative analysis of a 100-kb genomic interval containing two imprinted genes, PEG3 and ZIM2, using sequences derived from human, mouse, and cow. In all three mammals, ZIM2 is located at a similar genomic distance and in the same orientation relative to PEG3, indicating the basic structural conservation of this imprinted locus. However, several lineage-specific changes have occurred that affect the exon structure and imprinting status of ZIM2. Human ZIM2 and PEG3 share a set of 5' exons and a common promoter, and both genes are paternally expressed. In contrast, mouse and cow Zim2 genes do not share 5' exons with Peg3, and Zim2 employs a separate downstream promoter in both species. The imprinting status of Zim2 is also not conserved among mammals; mouse Zim2 is expressed biallelically in testis but predominantly from the maternal allele in brain, while cow Zim2 is expressed biallelically in testis. The separate transcription of Zim2 and Peg3 and the change in promoter usage and imprinting status appear to have resulted from independent insertional events that have placed unrelated genes, Zim1 and Ast1, respectively, between Zim2 and Peg3 in mouse and cow. Our results suggest that PEG3 and ZIM2 represent the two original genes at this locus and that rearrangements have occurred independently in different mammalian lineages in recent evolutionary times. Our data also suggest that exon-sharing of human PEG3 and ZIM2 was not ancestral, but may represent a fusion event joining the two neighboring genes and bringing ZIM2 under paternal expression control. These observations are striking in light of the structural and functional conservation that typifies other imprinted domains and suggest that the PEG3/ZIM2 imprinted domain may have evolved in an unusual lineage-specific pattern.
authors.affiliation: Genome Biology Division, Biology and Biotechnology Research Program, L-441, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94551, USA. kim16@llnl.gov
authors.forename: Joomyeong
authors.initials: J
authors.lastname: Kim
authors.forename: Anne
authors.initials: A
authors.lastname: Bergmann
authors.forename: Susan
authors.initials: S
authors.lastname: Lucas
authors.forename: Roger
authors.initials: R
authors.lastname: Stone
authors.forename: Lisa
authors.initials: L
authors.lastname: Stubbs
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics; D018392:Genomic Imprinting; D006801:Humans; D051741:Kruppel-Like Transcription Factors; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000235:genetics*; D016335:Zinc Fingers / Q000235:genetics*
chemical_list: D051741:Kruppel-Like Transcription Factors; C097901:Peg3 protein, mouse; D014157:Transcription Factors; C408894:ZIM2 protein, human; D011494:Protein Kinases