An evolutionary scenario for genomic imprinting of Impact lying between nonimprinted neighbors.

Mouse Impact is the sole imprinted gene mapped to chromosome 18 to date. Despite its remarkable evolutionary conservation, human IMPACT was shown to escape genomic imprinting. Here we identified Hrh4 and Osbpl1 as the distal and proximal nearest neighbors of Impact, respectively, and found that both genes are expressed biallelically. Thus, in contrast with most imprinted genes, Impact fails to show apparent physical clustering with other imprinted genes. Since Impact not only lies in an intergenic region but also consists of 11 exons, it does not seem to be an imprinted gene generated by a retrotransposition. Hazardous effects of overexpressed Impact, a genomic segment containing paralogues of Hrh4 and Osbpl1 but not of Impact, and enhanced promoter activity in the mouse led us to propose an alternative model. This model assumes that segmental duplication followed by enhancement of the promoter activity in the lineage to mouse is responsible for the species-specific imprinting of Impact.