repeated recruitment of ltr retrotransposons as promoters by the anti-apoptotic locus naip during mammalian evolution重复招聘ltr反转位子活动发起人的抗凋亡轨迹简要在哺乳动物进化.pdfVIP

Repeated Recruitment of LTR Retrotransposons as Promoters by the Anti-Apoptotic Locus NAIP during Mammalian Evolution Mark T. Romanish1,2, Wynne M. Lock1,2, Louie N. van de Lagemaat1,2, Catherine A. Dunn1,2¤, Dixie L. Mager1,2* 1 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, 2 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada Neuronal apoptosis inhibitory protein (NAIP, also known as BIRC1) is a member of the conserved inhibitor of apoptosis protein (IAP) family. Lineage-specific rearrangements and expansions of this locus have yielded different copy numbers among primates and rodents, with human retaining a single functional copy and mouse possessing several copies, depending on the strain. Roles for this gene in disease have been documented, but little is known about transcriptional regulation of NAIP. We show here that NAIP has multiple promoters sharing no similarity between human and rodents. Moreover, we demonstrate that multiple, domesticated long terminal repeats (LTRs) of endogenous retroviral elements provide NAIP promoter function in human, mouse, and rat. In human, an LTR serves as a tissue-specific promoter, active primarily in testis. However, in rodents, our evidence indicates that an ancestral LTR common to all rodent genes is the major, constitutive promoter for these genes, and that a second LTR found in two of the mouse genes is a minor promoter. Thus, independently acquired LTRs have assumed regulatory roles for orthologous genes, a remarkable evolutionary scenario. We also demonstrate that 59 flanking regions of IAP family genes as a group, in both human and mouse are enriched for LTR insertions compared to average genes. We propose several potential expla