ArticlePLoS computational biology2014
Synonymous constraint elements show a tendency to encode intrinsically disordered protein segments.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 23 citations in OpenAlex.
- Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Evolutionary Forces and Codon Bias in Different Flavors of Intrinsic Disorder in the Human Proteome.Journal of molecular evolution · 2020Article
- Human long intrinsically disordered protein regions are frequent targets of positive selection.Genome research · 2018Article
- Estimating the prevalence of functional exonic splice regulatory information.Human genetics · 2017Review
- Melting temperature highlights functionally important RNA structure and sequence elements in yeast mRNA coding regions.Nucleic acids research · 2017Article
- Both Maintenance and Avoidance of RNA-Binding Protein Interactions Constrain Coding Sequence Evolution.Molecular biology and evolution · 2017Article
- Codon usage is less optimized in eukaryotic gene segments encoding intrinsically disordered regions than in those encoding structural domains.Nucleic acids research · 2016Article
- Skipper genome sheds light on unique phenotypic traits and phylogeny.BMC genomics · 2015Article
- Splice junctions are constrained by protein disorder.Nucleic acids research · 2015Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synonymous constraint elements (SCEs) are protein-coding genomic regions with very low synonymous mutation rates believed to carry additional, overlapping functions. Thousands of such potentially multi-functional elements were recently discovered by analyzing the levels and patterns of evolutionary conservation in human coding exons. These elements provide a good opportunity to improve our understanding of how the redundant nature of the genetic code is exploited in the cell. Our premise is that the protein segments encoded by such elements might better comply with the increased functional demands if they are structurally less constrained (i.e. intrinsically disordered). To test this idea, we investigated the protein segments encoded by SCEs with computational tools to describe the underlying structural properties. In addition to SCEs, we examined the level of disorder, secondary structure, and sequence complexity of protein regions overlapping with experimentally validated splice regulatory sites. We show that multi-functional gene regions translate into protein segments that are significantly enriched in structural disorder and compositional bias, while they are depleted in secondary structure and domain annotations compared to reference segments of similar lengths. This tendency suggests that relaxed protein structural constraints provide an advantage when accommodating multiple overlapping functions in coding regions.
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