Substituição sinônima

Uma substituição sinônima (frequentemente chamada de substituição silenciosa, pois não produziria efeitos sensíveis, embora elas nem sempre sejam “silenciosas”) é a substituição evolutiva de uma base por outra em um éxon de um gene codificando para uma proteína, tal que a sequência de aminoácidos produzida não seja modificada. Isso é possível porque o código genético é "degenerado", o que significa que alguns aminoácidos são codificados por mais de um par de códon de três bases; já que alguns dos códons de um determinado aminoácido diferem em apenas um par de bases de outros que codificam o mesmo aminoácido, uma mutação que substitui a base "normal" por uma das alternativas resultará na incorporação do mesmo aminoácido na cadeia polipeptídica em crescimento quando o gene é traduzido. Substituições sinônimas e mutações afetando DNA não codificante são frequentemente consideradas mutações silenciosas; no entanto, nem sempre é o caso que a mutação é silenciosa.[1][2][3][4][5] Substituições sinônimas podem afetar transcrição, splicing, transporte de mRNA e tradução, qualquer um dos quais poderia alterar o fenótipo, tornando a mutação sinônima não silenciosa.[3] A especificidade de substrato do tRNA ao códon raro que pode afetar o tempo de tradução e, por sua vez, o dobramento co-translacional da proteína.[1] Isso se reflete no viés de uso de código (abreviado na literatura como RSCU, do inglês relative synonymous codon usage) que é observado em muitas espécies.Uma substituição não sinônima resulta em uma mudança no aminoácido que pode ser ainda classificada arbitrariamente como conservativa (mudança para um aminoácido com propriedades físico-químicas similares), semi-conservativa (e.g. aminoácido negativa ou positivamente carregado), ou radical (aminoácido muito diferente).

Referências

  1. ↑ a b Kimchi-Sarfaty, C.; Oh, J. M.; Kim, I.-W.; Sauna, Z. E.; Calcagno, A. M.; Ambudkar, S. V.; Gottesman, M. M. (26 de janeiro de 2007). «A "Silent" Polymorphism in the MDR1 Gene Changes Substrate Specificity». Science. 315 (5811): 525–8. PMID 17185560. doi:10.1126/science.1135308 
  2. ↑ Chamary, JV; Parmley, JL; Hurst, LD (fevereiro de 2006). «Hearing silence: non-neutral evolution at synonymous sites in mammals.». Nature Reviews Genetics. 7 (2): 98–108. PMID 16418745. doi:10.1038/nrg1770 
  3. ↑ a b Goymer, Patrick (fevereiro de 2007). «Synonymous mutations break their silence». Nature Reviews Genetics. 8 (2): 92. doi:10.1038/nrg2056 
  4. ↑ Zhou, Tong; Ko, Eun A.; Gu, Wanjun; Lim, Inja; Bang, Hyoweon; Ko, Jae-Hong; Uversky, Vladimir N. (31 de outubro de 2012). «Non-Silent Story on Synonymous Sites in Voltage-Gated Ion Channel Genes». PLoS ONE. 7 (10): e48541. PMC 3485311Acessível livremente. PMID 23119053. doi:10.1371/journal.pone.0048541 
  5. ↑ Graur, Dan (2003). «Single Base Mutation» (PDF). In: Cooper, David N. Nature Encyclopedia of the Human Genome (PDF). [S.l.]: MacMillan. ISBN 0333803868 

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