Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts

Despite evidence that at the interspecific scale, exonic splicing silencers (ESSs) are under negative selection in constitutive exons, little is known about the effects of slightly deleterious polymorphisms on these splicing regulators. Through the application of a modified version of the McDon...

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Principais autores: Ramalho, Rodrigo F., Gelfman, Sahar, Souza, Jorge E. de, Ast, Gil, Souza, Sandro José de, Meyer, Diogo
Formato: article
Idioma:eng
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Assuntos:
Alternative splicing
Human polymorphism
Exonic splicing regulators
MK test
Endereço do item:https://repositorio.ufrn.br/jspui/handle/123456789/23332
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spelling ri-123456789-233322021-07-09T22:47:42Z Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts Ramalho, Rodrigo F. Gelfman, Sahar Souza, Jorge E. de Ast, Gil Souza, Sandro José de Meyer, Diogo Alternative splicing Human polymorphism Exonic splicing regulators MK test Despite evidence that at the interspecific scale, exonic splicing silencers (ESSs) are under negative selection in constitutive exons, little is known about the effects of slightly deleterious polymorphisms on these splicing regulators. Through the application of a modified version of the McDonald–Kreitman test, we compared the normalized proportions of human polymorphisms and human/rhesus substitutions affecting exonic splicing regulators (ESRs) on sequences of constitutive and alternative exons. Our results show a depletion of substitutions and an enrichment of SNPs associated with ESS gain in constitutive exons. Moreover, we show that this evolutionary pattern is also present in a set of ESRs previously involved in the transition from constitutive to skipped exons in the mammalian lineage. The similarity between these two sets of ESRs suggests that the transition from constitutive to skipped exons in mammals is more frequently associated with the inhibition than with the promotion of splicing signals. This is in accordance with the hypothesis of a constitutive origin of exon skipping and corroborates previous findings about the antagonistic role of certain exonic splicing enhancers. 2017-06-01T12:44:19Z 2017-06-01T12:44:19Z 2013 article 0022-2844 https://repositorio.ufrn.br/jspui/handle/123456789/23332 eng Acesso Aberto application/pdf
institution Repositório Institucional
collection RI - UFRN
language eng
topic Alternative splicing
Human polymorphism
Exonic splicing regulators
MK test
spellingShingle Alternative splicing
Human polymorphism
Exonic splicing regulators
MK test
Ramalho, Rodrigo F.
Gelfman, Sahar
Souza, Jorge E. de
Ast, Gil
Souza, Sandro José de
Meyer, Diogo
Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts
description Despite evidence that at the interspecific scale, exonic splicing silencers (ESSs) are under negative selection in constitutive exons, little is known about the effects of slightly deleterious polymorphisms on these splicing regulators. Through the application of a modified version of the McDonald–Kreitman test, we compared the normalized proportions of human polymorphisms and human/rhesus substitutions affecting exonic splicing regulators (ESRs) on sequences of constitutive and alternative exons. Our results show a depletion of substitutions and an enrichment of SNPs associated with ESS gain in constitutive exons. Moreover, we show that this evolutionary pattern is also present in a set of ESRs previously involved in the transition from constitutive to skipped exons in the mammalian lineage. The similarity between these two sets of ESRs suggests that the transition from constitutive to skipped exons in mammals is more frequently associated with the inhibition than with the promotion of splicing signals. This is in accordance with the hypothesis of a constitutive origin of exon skipping and corroborates previous findings about the antagonistic role of certain exonic splicing enhancers.
format article
author Ramalho, Rodrigo F.
Gelfman, Sahar
Souza, Jorge E. de
Ast, Gil
Souza, Sandro José de
Meyer, Diogo
author_facet Ramalho, Rodrigo F.
Gelfman, Sahar
Souza, Jorge E. de
Ast, Gil
Souza, Sandro José de
Meyer, Diogo
author_sort Ramalho, Rodrigo F.
title Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts
title_short Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts
title_full Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts
title_fullStr Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts
title_full_unstemmed Testing for Natural Selection in Human Exonic Splicing Regulators Associated with Evolutionary Rate Shifts
title_sort testing for natural selection in human exonic splicing regulators associated with evolutionary rate shifts
publishDate 2017
url https://repositorio.ufrn.br/jspui/handle/123456789/23332
work_keys_str_mv AT ramalhorodrigof testingfornaturalselectioninhumanexonicsplicingregulatorsassociatedwithevolutionaryrateshifts
AT gelfmansahar testingfornaturalselectioninhumanexonicsplicingregulatorsassociatedwithevolutionaryrateshifts
AT souzajorgeede testingfornaturalselectioninhumanexonicsplicingregulatorsassociatedwithevolutionaryrateshifts
AT astgil testingfornaturalselectioninhumanexonicsplicingregulatorsassociatedwithevolutionaryrateshifts
AT souzasandrojosede testingfornaturalselectioninhumanexonicsplicingregulatorsassociatedwithevolutionaryrateshifts
AT meyerdiogo testingfornaturalselectioninhumanexonicsplicingregulatorsassociatedwithevolutionaryrateshifts
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