ArticleNucleic acids research2014
Exonic splicing signals impose constraints upon the evolution of enzymatic activity.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Rescue of a panel of Hemophilia A-causing 5'ss splicing mutations by unique Exon-specific U1snRNA variants.Molecular medicine (Cambridge, Mass.) · 2025Article
- Dissection of pleiotropic effects of variants in and adjacent to F8 exon 19 and rescue of mRNA splicing and protein function.American journal of human genetics · 2021Article
- Both Maintenance and Avoidance of RNA-Binding Protein Interactions Constrain Coding Sequence Evolution.Molecular biology and evolution · 2017Article
- Thioesterase domain swapping of a linear polyketide tautomycetin with a macrocyclic polyketide pikromycin in Streptomyces sp. CK4412.Journal of industrial microbiology & biotechnology · 2016Article
- Introns Structure Patterns of Variation in Nucleotide Composition in Arabidopsis thaliana and Rice Protein-Coding Genes.Genome biology and evolution · 2015Article
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Authors and funding
7 authors at 3 institutions in 4 countries.
Funding
Abstract
Exon splicing enhancers (ESEs) overlap with amino acid coding sequences implying a dual evolutionary selective pressure. In this study, we map ESEs in the placental alkaline phosphatase gene (ALPP), absent in the corresponding exon of the ancestral tissue-non-specific alkaline phosphatase gene (ALPL). The ESEs are associated with amino acid differences between the transcripts in an area otherwise conserved. We switched out the ALPP ESEs sequences with the sequence from the related ALPL, introducing the associated amino acid changes. The resulting enzymes, produced by cDNA expression, showed different kinetic characteristics than ALPL and ALPP. In the organism, this enzyme will never be subjected to selection because gene splicing analysis shows exon skipping due to loss of the ESE. Our data prove that ESEs restrict the evolution of enzymatic activity. Thus, suboptimal proteins may exist in scenarios when coding nucleotide changes and consequent amino acid variation cannot be reconciled with the splicing function.
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Registered trials
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