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Open Access Research article

Frame disruptions in human mRNA transcripts, and their relationship with splicing and protein structures

Paul Harrison* and Zhan Yu

Author Affiliations

Department of Biology, McGill University, Stewart Biology Building, 1205 Docteur Penfield Ave., Montreal, QC, H3A 1B1 Canada

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BMC Genomics 2007, 8:371  doi:10.1186/1471-2164-8-371

Published: 15 October 2007

Abstract

Background

Efforts to gather genomic evidence for the processes of gene evolution are ongoing, and are closely coupled to improved gene annotation methods. Such annotation is complicated by the occurrence of disrupted mRNAs (dmRNAs), harbouring frameshifts and premature stop codons, which can be considered indicators of decay into pseudogenes.

Results

We have derived a procedure to annotate dmRNAs, and have applied it to human data. Subsequences are generated from parsing at key frame-disruption positions and are required to align significantly within any original protein homology. We find 419 high-quality human dmRNAs (3% of total). Significant dmRNA subpopulations include: zinc-finger-containing transcription factors with long disrupted exons, and antisense homologies to distal genes. We analysed the distribution of initial frame disruptions in dmRNAs with respect to positions of: (i) protein domains, (ii) alternatively-spliced exons, and (iii) regions susceptible to nonsense-mediated decay (NMD). We find significant avoidance of protein-domain disruption (indicating a selection pressure for this), and highly significant overrepresentation of disruptions in alternatively-spliced exons, and 'non-NMD' regions. We do not find any evidence for evolution of novelty in protein structures through frameshifting.

Conclusion

Our results indicate largely negative selection pressures related to frame disruption during gene evolution.