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

Harrison P, Yu Z - BMC Genomics (2007)

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

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, McGill University, Stewart Biology Building, 1205 Docteur Penfield Ave,, Montreal, QC, H3A 1B1 Canada. paul.harrison@mcgill.ca

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.

Show MeSH

Related in: MedlinePlus

Pipeline for annotating dmRNAs. The steps discussed in Methods are illustrated schematically.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2194788&req=5

Figure 5: Pipeline for annotating dmRNAs. The steps discussed in Methods are illustrated schematically.

Mentions: It is possible that through analysis of this comprehensive data set of dmRNAs, that we can find evidence for a positive role for such protein-coding frame disruptions in gene evolution. Specifically, is there evidence that such frame-shifts can produce significant structural novelties? To check this, we derived a modification for the initial pipeline (Figure 5), with matches to SCOP protein structure domains replacing those for whole protein sequences from the SWISSPROT database, finding 36 cases (9% of the dmRNAs) which produce a significant alignment for both subsequences delimited by the initial frameshift (Figure 5, step 3). However, none of these (0%) overlap another protein domain assignment in a different frame, yielding no evidence for generation of protein structure novelties through single frameshifts. Nonetheless, a more thorough analysis of multiple vertebrates would be required to provide a more conclusive perspective on the role of frameshift in protein structure evolution.


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

Harrison P, Yu Z - BMC Genomics (2007)

Pipeline for annotating dmRNAs. The steps discussed in Methods are illustrated schematically.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2194788&req=5

Figure 5: Pipeline for annotating dmRNAs. The steps discussed in Methods are illustrated schematically.
Mentions: It is possible that through analysis of this comprehensive data set of dmRNAs, that we can find evidence for a positive role for such protein-coding frame disruptions in gene evolution. Specifically, is there evidence that such frame-shifts can produce significant structural novelties? To check this, we derived a modification for the initial pipeline (Figure 5), with matches to SCOP protein structure domains replacing those for whole protein sequences from the SWISSPROT database, finding 36 cases (9% of the dmRNAs) which produce a significant alignment for both subsequences delimited by the initial frameshift (Figure 5, step 3). However, none of these (0%) overlap another protein domain assignment in a different frame, yielding no evidence for generation of protein structure novelties through single frameshifts. Nonetheless, a more thorough analysis of multiple vertebrates would be required to provide a more conclusive perspective on the role of frameshift in protein structure evolution.

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

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biology, McGill University, Stewart Biology Building, 1205 Docteur Penfield Ave,, Montreal, QC, H3A 1B1 Canada. paul.harrison@mcgill.ca

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.

Show MeSH
Related in: MedlinePlus