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

@entity1 @entity1547 @entity219
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 @entity1 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 @entity1 dmRNAs (3% of total). Significant dmRNA subpopulations include: @entity219 -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 @entity1547 ( @entity1547 ). 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- @entity1547 ' 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.
