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Exonic splicing signals impose constraints upon the evolution of enzymatic activity

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...

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Autores principales: Falanga, Alessia, Stojanović, Ozren, Kiffer-Moreira, Tina, Pinto, Sofia, Millán, José Luis, Vlahoviček, Kristian, Baralle, Marco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027185/
https://www.ncbi.nlm.nih.gov/pubmed/24692663
http://dx.doi.org/10.1093/nar/gku240
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author Falanga, Alessia
Stojanović, Ozren
Kiffer-Moreira, Tina
Pinto, Sofia
Millán, José Luis
Vlahoviček, Kristian
Baralle, Marco
author_facet Falanga, Alessia
Stojanović, Ozren
Kiffer-Moreira, Tina
Pinto, Sofia
Millán, José Luis
Vlahoviček, Kristian
Baralle, Marco
author_sort Falanga, Alessia
collection PubMed
description 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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spelling pubmed-40271852014-05-28 Exonic splicing signals impose constraints upon the evolution of enzymatic activity Falanga, Alessia Stojanović, Ozren Kiffer-Moreira, Tina Pinto, Sofia Millán, José Luis Vlahoviček, Kristian Baralle, Marco Nucleic Acids Res Molecular Biology 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. Oxford University Press 2014-05-01 2014-04-01 /pmc/articles/PMC4027185/ /pubmed/24692663 http://dx.doi.org/10.1093/nar/gku240 Text en © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Molecular Biology
Falanga, Alessia
Stojanović, Ozren
Kiffer-Moreira, Tina
Pinto, Sofia
Millán, José Luis
Vlahoviček, Kristian
Baralle, Marco
Exonic splicing signals impose constraints upon the evolution of enzymatic activity
title Exonic splicing signals impose constraints upon the evolution of enzymatic activity
title_full Exonic splicing signals impose constraints upon the evolution of enzymatic activity
title_fullStr Exonic splicing signals impose constraints upon the evolution of enzymatic activity
title_full_unstemmed Exonic splicing signals impose constraints upon the evolution of enzymatic activity
title_short Exonic splicing signals impose constraints upon the evolution of enzymatic activity
title_sort exonic splicing signals impose constraints upon the evolution of enzymatic activity
topic Molecular Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027185/
https://www.ncbi.nlm.nih.gov/pubmed/24692663
http://dx.doi.org/10.1093/nar/gku240
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