MBE Advance Access originally published online on March 12, 2009
Molecular Biology and Evolution 2009 26(6):1321-1332; doi:10.1093/molbev/msp047
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Research Articles |
The NBPF1 Promoter Has Been Recruited from the Unrelated EVI5 Gene Before Simian Radiation
Department for Molecular Biomedical Research, Flanders Institute for Biotechnology (VIB), Ghent, Belgium
Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
E-mail: f.vanroy{at}dmbr.ugent.be.
Accepted for publication March 2, 2009.
Most new genes arise through the duplication of existing genes. In most cases, the duplication is not limited to the coding sequence but encompasses the regulatory region as well. The NBPF gene family has expanded during recent primate evolution, and it has no known mouse ortholog. One of its members, NBPF1, was found to be disrupted by a constitutional translocation in a neuroblastoma patient. Here, we show that the ancestral NBPF gene copied the regulatory region from an unrelated gene, EVI5, after the split between simians and prosimians but before simian radiation. Phylogenetic analysis points to the possible involvement of positive selection acting on the NBPF1 promoter in the simian lineage. We previously showed decreased NBPF1 expression in certain neuroblastoma cell lines. Here, we show that this expression pattern is mimicked by the EVI5 gene, but partly by different mechanisms. Epigenetic regulation of the EVI5 promoter is common in neuroblastoma cell lines, but it is not for the NBPF promoters. Here, we describe the recent acquisition of the NBPF1 promoter from an unrelated gene, and remarkably, both the donor (EVI5) and acceptor (NBPF1) genes are disrupted by constitutional translocations in patients with neuroblastoma, suggesting a functional link between these genes and the disease.
Key Words: NBPF • EVI5 • promoter • duplication
Naruya Saitou, Associate Editor