distributions of transposable elements reveal hazardous zones in mammalian introns转位因子的分布揭示了在哺乳动物的基因内区危险区域.pdfVIP

Distributions of Transposable Elements Reveal Hazardous Zones in Mammalian Introns Ying Zhang1,2, Mark T. Romanish1,2, Dixie L. Mager1,2* 1Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, British Columbia, Canada, 2 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada Abstract Comprising nearly half of the human and mouse genomes, transposable elements (TEs) are found within most genes. Although the vast majority of TEs in introns are fixed in the species and presumably exert no significant effects on the enclosing gene, some markedly perturb transcription and result in disease or a mutated phenotype. Factors determining the likelihood that an intronic TE will affect transcription are not clear. In this study, we examined intronic TE distributions in both human and mouse and found several factors that likely contribute to whether a particular TE can influence gene transcription. Specifically, we observed that TEs near exons are greatly underrepresented compared to random distributions, but the size of these ‘‘underrepresentation zones’’ differs between TE classes. Compared to elsewhere in introns, TEs within these zones are shorter on average and show stronger orientation biases. Moreover, TEs in extremely close proximity (,20 bp) to exons show a strong bias to be near splice-donor sites. Interestingly, disease-causing intronic TE insertions show the opposite distributional trends, and by examining expressed sequence tag (EST) databases, we found that the proportion of TEs contributing to chimeric TE-gene transcripts is significantly higher within their underrepresentation zones. In addition, an analysis of predicted splice sites within human long terminal repeat (LTR) elements showed a significantly