Abstract
BackgroundEfforts 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.ResultsWe 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.ConclusionOur results indicate largely negative selection pressures related to frame disruption during gene evolution.
Highlights
Efforts to gather genomic evidence for the processes of gene evolution are ongoing, and are closely coupled to improved gene annotation methods
Our results indicate largely negative selection pressures related to frame disruption during gene evolution
A small subpopulation of these (419, or 3% of the total) mRNAs harbour significant frame disruptions (Table 1), which is of a similar order to previous analyses of such disruptions in sets of transcripts [16,2,9]
Summary
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. Retropseudogenes are copies of messenger RNAs that have been reverse-transcribed and re-integrated into the genome, probably as a by-product of LINE-1 retrotransposition [4] These intronless copies of genes usually decay and are deleted from the genomic DNA [1,5,6,7,8,3]. Some retropseudogenes are transcribed, perhaps through co-option of local promoter elements, as supported by their increased density near genes [2,9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
