Transposable element fragments in protein-coding regions and their contributions to human functional proteins.
ABSTRACT Transposable elements (TEs) and their contributions to protein-coding regions are of particular interest. Here we searched for TE fragments in Homo sapiens at both the transcript and protein levels. We found evidence in support of TE exonization and its association with alternative splicing. Despite recent findings that long evolutionary times are required to incorporate TE into proteins, we found many functional proteins with translated TE cassettes derived from young TEs. Analyses of two Bcl-family proteins and Alu-encoded segments suggest the coding and functional potential of TE sequences.
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ABSTRACT: Insertion of transposable elements (TEs) into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Exonization can enrich the complexity of transcriptomes and proteomes. Previously, we performed a genome-wide computational analysis of Ds exonization events in the monocot Oryza sativa (rice). The insertion patterns of Ds increased the number of transcripts and subsequent protein isoforms, which were determined as interior and C-terminal variants. In this study, these variants were scanned with the PROSITE database in order to identify new functional profiles (domains) that were referred to their reference proteins. The new profiles of the variants were expected to be beneficial for a selective advantage and more than 70% variants achieved this. The new functional profiles could be contributed by an exon-intron junction, an intron alone, an intron-TE junction, or a TE alone. A Ds-inserted intron may yield 167 new profiles on average, while some cases can yield thousands of new profiles, of which C-terminal variants were in major. Additionally, more than 90% of the TE-inserted genes were found to gain novel functional profiles in each intron via exonization. Therefore, new functional profiles yielded by the exonization may occur in many local regions of the reference protein.Evolutionary bioinformatics online 10/2013; 9:417-27. DOI:10.4137/EBO.S12757 · 1.17 Impact Factor
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ABSTRACT: Repetitive elements, which are relics of previous transposition events, constitute a large proportion of the human genome. The ability of transposons to gives rise to new DNA combinations has clearly provided an evolutionary advantage to their hosts. Transposons have shaped our genomes by giving rise to novel coding sequences, alternative gene promoters, conserved noncoding elements, and gene networks. Despite its benefits, the process of transposition can also create deleterious DNA combinations, and a growing number of human diseases are being linked to abnormal repetitive element activity. To limit transposition, cells tightly regulate and immobilize repetitive elements using DNA methylation and other epigenetic marks. Recent findings in neuropsychiatric disorders implicate both repetitive elements and epigenetic marks as potential etiological factors. It is possible that these observations are linked and that the reported alterations in epigenetic marks may create a permissive state enabling transposons to mobilize. In this work, we provide a detailed description of repetitive element biology and epigenetics to familiarize the readers with the subject matter and to illustrate how their disruption can result in pathology. We also review the evidence for the involvement of these two factors in neuropsychiatric disorders and discuss the need for replication studies to confirm these initial findings. We are cautiously optimistic that further characterization of epigenetic mark and repetitive element activity in the brain will reveal the underlying causes of schizophrenia, bipolar disorder, and major depression.Advances in genetics 01/2014; 86C:185-252. DOI:10.1016/B978-0-12-800222-3.00009-7 · 5.41 Impact Factor