Biased exonization of transposed elements in duplicated genes: A lesson from the TIF-IA gene

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dc.creatorAmit, Maayan
dc.creatorSela, Noa
dc.creatorKeren, Hadas
dc.creatorMelamed, Zeev
dc.creatorMuler, Inna
dc.creatorShomron, Noam
dc.creatorIzraeli, Shai
dc.creatorAst, Gil
dc.date2008-11-21
dc.date.accessioned2026-07-07T10:20:04Z
dc.date.available2026-07-07T10:20:04Z
dc.descriptionBackground: Gene duplication and exonization of intronic transposed elements are two mechanisms that enhance genomic diversity. We examined whether there is less selection against exonization of transposed elements in duplicated genes than in single-copy genes. Results: Genome-wide analysis of exonization of transposed elements revealed a higher rate of exonization within duplicated genes relative to single-copy genes. The gene for TIF-IA, an RNA polymerase I transcription initiation factor, underwent a humanoid-specific triplication, all three copies of the gene are active transcriptionally, although only one copy retains the ability to generate the TIF-IA protein. Prior to TIF-IA triplication, an Alu element was inserted into the first intron. In one of the non-protein coding copies, this Alu is exonized. We identified a single point mutation leading to exonization in one of the gene duplicates. When this mutation was introduced into the TIF-IA coding copy, exonization was activated and the level of the protein-coding mRNA was reduced substantially. A very low level of exonization was detected in normal human cells. However, this exonization was abundant in most leukemia cell lines evaluated, although the genomic sequence is unchanged in these cancerous cells compared to normal cells. Conclusion: The definition of the Alu element within the TIF-IA gene as an exon is restricted to certain types of cancers; the element is not exonized in normal human cells. These results further our understanding of the delicate interplay between gene duplication and alternative splicing and of the molecular evolutionary mechanisms leading to genetic innovations. This implies the existence of purifying selection against exonization in single copy genes, with duplicate genes free from such constrains.
dc.identifierhttps://arxiv.org/abs/0811.3507
dc.identifierhttp://arxiv.org/abs/0811.3507
dc.identifierBMC Molecular Biology 2007, 8:109
dc.identifierdoi:10.1186/1471-2199-8-109
dc.identifier.urihttp://salesiana.dossiersoluciones.com/handle/123456789/174736
dc.subjectGenomics
dc.subjectPopulations and Evolution
dc.titleBiased exonization of transposed elements in duplicated genes: A lesson from the TIF-IA gene
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