Non-silent story on synonymous sites in voltage-gated ion channel genes.

Synonymous mutations are usually referred to as "silent", but increasing evidence shows that they are not neutral in a wide range of organisms. We looked into the relationship between synonymous codon usage bias and residue importance of voltage-gated ion channel proteins in mice, rats, an...

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Autores principales:	Tong Zhou, Eun A Ko, Wanjun Gu, Inja Lim, Hyoweon Bang, Jae-Hong Ko
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6a8352c3e2f84ea59e6e78921f9c1cfb
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spelling	oai:doaj.org-article:6a8352c3e2f84ea59e6e78921f9c1cfb2021-11-18T08:10:20ZNon-silent story on synonymous sites in voltage-gated ion channel genes.1932-620310.1371/journal.pone.0048541https://doaj.org/article/6a8352c3e2f84ea59e6e78921f9c1cfb2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23119053/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Synonymous mutations are usually referred to as "silent", but increasing evidence shows that they are not neutral in a wide range of organisms. We looked into the relationship between synonymous codon usage bias and residue importance of voltage-gated ion channel proteins in mice, rats, and humans. We tested whether translationally optimal codons are associated with transmembrane or channel-forming regions, i.e., the sites that are particularly likely to be involved in the closing and opening of an ion channel. Our hypothesis is that translationally optimal codons are preferred at the sites within transmembrane domains or channel-forming regions in voltage-gated ion channel genes to avoid mistranslation-induced protein misfolding or loss-of-function. Using the Mantel-Haenszel procedure, which applies to categorical data, we found that translationally optimal codons are more likely to be used at transmembrane residues and the residues involved in channel-forming. We also found that the conservation level at synonymous sites in the transmembrane region is significantly higher than that in the non-transmembrane region. This study provides evidence that synonymous sites in voltage-gated ion channel genes are not neutral. Silent mutations at channel-related sites may lead to dysfunction of the ion channel.Tong ZhouEun A KoWanjun GuInja LimHyoweon BangJae-Hong KoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e48541 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tong Zhou Eun A Ko Wanjun Gu Inja Lim Hyoweon Bang Jae-Hong Ko Non-silent story on synonymous sites in voltage-gated ion channel genes.
description	Synonymous mutations are usually referred to as "silent", but increasing evidence shows that they are not neutral in a wide range of organisms. We looked into the relationship between synonymous codon usage bias and residue importance of voltage-gated ion channel proteins in mice, rats, and humans. We tested whether translationally optimal codons are associated with transmembrane or channel-forming regions, i.e., the sites that are particularly likely to be involved in the closing and opening of an ion channel. Our hypothesis is that translationally optimal codons are preferred at the sites within transmembrane domains or channel-forming regions in voltage-gated ion channel genes to avoid mistranslation-induced protein misfolding or loss-of-function. Using the Mantel-Haenszel procedure, which applies to categorical data, we found that translationally optimal codons are more likely to be used at transmembrane residues and the residues involved in channel-forming. We also found that the conservation level at synonymous sites in the transmembrane region is significantly higher than that in the non-transmembrane region. This study provides evidence that synonymous sites in voltage-gated ion channel genes are not neutral. Silent mutations at channel-related sites may lead to dysfunction of the ion channel.
format	article
author	Tong Zhou Eun A Ko Wanjun Gu Inja Lim Hyoweon Bang Jae-Hong Ko
author_facet	Tong Zhou Eun A Ko Wanjun Gu Inja Lim Hyoweon Bang Jae-Hong Ko
author_sort	Tong Zhou
title	Non-silent story on synonymous sites in voltage-gated ion channel genes.
title_short	Non-silent story on synonymous sites in voltage-gated ion channel genes.
title_full	Non-silent story on synonymous sites in voltage-gated ion channel genes.
title_fullStr	Non-silent story on synonymous sites in voltage-gated ion channel genes.
title_full_unstemmed	Non-silent story on synonymous sites in voltage-gated ion channel genes.
title_sort	non-silent story on synonymous sites in voltage-gated ion channel genes.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/6a8352c3e2f84ea59e6e78921f9c1cfb
work_keys_str_mv	AT tongzhou nonsilentstoryonsynonymoussitesinvoltagegatedionchannelgenes AT eunako nonsilentstoryonsynonymoussitesinvoltagegatedionchannelgenes AT wanjungu nonsilentstoryonsynonymoussitesinvoltagegatedionchannelgenes AT injalim nonsilentstoryonsynonymoussitesinvoltagegatedionchannelgenes AT hyoweonbang nonsilentstoryonsynonymoussitesinvoltagegatedionchannelgenes AT jaehongko nonsilentstoryonsynonymoussitesinvoltagegatedionchannelgenes
_version_	1718422112424689664

Non-silent story on synonymous sites in voltage-gated ion channel genes.

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