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MBE Advance Access published online on May 18, 2005
Molecular Biology and Evolution, doi:10.1093/molbev/msi165
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© The Author 2005. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org
Accepted May 13, 2005

Research Article

Comparative Phylogenetic Analysis of Blcap/Nnat Reveals Eutherian-Specific Imprinted Gene

Heather K. Evans 1, Jennifer R. Weidman 1, Dale O. Cowley 2, and Randy L. Jirtle 1*

1 Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710; University Program in Genetics and Genomics, Duke University Medical Center, Durham, NC 27710
2 Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599

* To whom correspondence should be addressed.
Randy L. Jirtle, E-mail: jirtle{at}radonc.duke.edu


  Abstract

Imprinted genes are parent-of-origin dependent, monoallelically expressed genes present in marsupials and eutherian mammals. Altered expression of imprinted genes plays a significant role in the etiology of a variety of human disorders and diseases. Nevertheless, the regulatory mechanisms of imprinting remain poorly defined. The imprinted gene Neuronatin (Nnat) is an excellent candidate for studying imprinting because it resides within the 8.5 kb intron of the non-imprinted gene Blcap and is the only imprinted gene within the region. A phylogenetic comparison of this micro-imprinted domain in human, mouse, and rat revealed several candidates for imprint control, including tandem repeats and putative binding sites for trans-acting factors known to be involved in chromatin remodeling. Genome-wide phylogenetic comparisons of species from the three major extant mammalian clades failed, however, to show any evidence of Nnat outside the eutherian lineage. Thus, Nnat is the first identified eutherian-specific imprinted gene, demonstrating that imprinted genes did not arise at a single point during evolution. This finding also suggests that the complexity of imprinting regulation observed at other loci may, in part, be directly related to the amount of time they have been imprinted.

Keywords: Blcap; eutherian; evolution; imprinting; Nnat; phylogenetics.
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