non-silent story on synonymous sites in voltage-gated ion channel genesnon-silent故事的网站在电压门控离子通道基因.pdfVIP

Non-Silent Story on Synonymous Sites in Voltage-Gated Ion Channel Genes 1,2. 3. 4 5 5 5 Tong Zhou , Eun A. Ko , Wanjun Gu , Inja Lim , Hyoweon Bang , Jae-Hong Ko * 1 Institute for Personalized Respiratory Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America, 2 Section of Pulmonary, Critical Care, Sleep Allergy, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America, 3 Department of Medicine, University of California San Francisco, San Francisco, California, United States of America, 4 Key Laboratory of Child Development and Learning Science of Ministry of Education of China, Southeast University, Nanjing, Jiangsu, China, 5 Department of Physiology, College of Medicine, Chung-Ang University, Seoul, South Korea Abstract 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