Skip to main content
ARS Home » Plains Area » Clay Center, Nebraska » U.S. Meat Animal Research Center » Genetics and Animal Breeding » Research » Publications at this Location » Publication #155694
Title: LINEAGE-SPECIFIC IMPRINTING AND EVOLUTION OF THE ZINC FINGER GENE ZIM2

Author
item KIM, JOOMYEONG - LAWRENCE LIVERMORE LAB
item BERGMANN, ANNE - LAWRENCE LIVERMORE LAB
item LUCAS, SUSAN - DOE JOINT GENOME INST.
item Stone, Roger
item STUBBS, LISA - LAWRENCE LIVERMORE LAB

Submitted to: Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/11/2004
Publication Date: 7/1/2004
Citation: Kim, J., Bergmann, A., Lucas, S., Stone, R.T., Stubbs, L. 2004. Lineage-specific imprinting and evolution of the zinc finger gene ZIM2. Genomics. 84(1):47-58.

Interpretive Summary: Genes in several regions of the mammalian genome are imprinted: That is, one of the parental genes will be silenced leaving only the paternal or maternal copy of the gene to be expressed. Most studies have been done in humans and mice. Prior to this current study the only imprinted region to be subjected to detailed sequence and expression analysis in domestic animals was a locus in sheep where a single base mutation results in muscle hypertrophy. Expression patterns and sequence in this imprinted region are highly conserved in mice, human and sheep. In contrast, the imprinted region targeted in this current study varies dramatically between mice, humans and cows which suggest that each linage has undergone independent rearrangements that have resulted in differences in imprinting, expression, and status. This finding underscores the need for detailed analysis in target species. Inference from model organisms is not always sufficient. The possible role of imprinting in agronomic traits has been largely ignored because of a lack of molecular tools. This has changed rapidly in the last two years as illustrated in a recent report of a quantitative trait loci (QTL) effecting muscle mass in swine being mapped to a small (250 kb) imprinted region of the swine genome.

Technical Abstract: We have carried out an in-depth comparative analysis of a 100-kb genomic interval containing two imprinted genes, paternally expressed gene 3 (PEG3) and imprinted zinc-finger gene 2 (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 bi-allelically in testis but predominantly from the maternal allele in brain, while cow Zim2 is expressed biallelically in testis. The separate transcription of ZIM2 from 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 artiodactyl-specific transcript 1 (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.