Your browser doesn't support javascript.
loading
Highly heterogeneous mutation rates in the hepatitis C virus genome.
Geller, Ron; Estada, Úrsula; Peris, Joan B; Andreu, Iván; Bou, Juan-Vicente; Garijo, Raquel; Cuevas, José M; Sabariegos, Rosario; Mas, Antonio; Sanjuán, Rafael.
Afiliação
  • Geller R; Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Institute for Integrative Systems Biology (I2SysBio), Universitat de València, 46980 Paterna, València, Spain.
  • Estada Ú; Unitat de Genómica, Servei Central de Suport a la Investigació Experimental, Universitat de València, 46100 Burjassot, València, Spain.
  • Peris JB; Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Institute for Integrative Systems Biology (I2SysBio), Universitat de València, 46980 Paterna, València, Spain.
  • Andreu I; Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Institute for Integrative Systems Biology (I2SysBio), Universitat de València, 46980 Paterna, València, Spain.
  • Bou JV; Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Institute for Integrative Systems Biology (I2SysBio), Universitat de València, 46980 Paterna, València, Spain.
  • Garijo R; Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Institute for Integrative Systems Biology (I2SysBio), Universitat de València, 46980 Paterna, València, Spain.
  • Cuevas JM; Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Institute for Integrative Systems Biology (I2SysBio), Universitat de València, 46980 Paterna, València, Spain.
  • Sabariegos R; Regional Center for Biomedical Research, Universidad de Castilla-La Mancha, 02006 Albacete, Spain.
  • Mas A; Regional Center for Biomedical Research, Universidad de Castilla-La Mancha, 02006 Albacete, Spain.
  • Sanjuán R; Instituto Cavanilles de Biodiversidad y Biología Evolutiva and Institute for Integrative Systems Biology (I2SysBio), Universitat de València, 46980 Paterna, València, Spain.
Nat Microbiol ; 1(7): 16045, 2016 04 18.
Article em En | MEDLINE | ID: mdl-27572964
Spontaneous mutations are the ultimate source of genetic variation and have a prominent role in evolution. RNA viruses such as hepatitis C virus (HCV) have extremely high mutation rates, but these rates have been inferred from a minute fraction of genome sites, limiting our view of how RNA viruses create diversity. Here, by applying high-fidelity ultradeep sequencing to a modified replicon system, we scored >15,000 spontaneous mutations, encompassing more than 90% of the HCV genome. This revealed >1,000-fold differences in mutability across genome sites, with extreme variations even between adjacent nucleotides. We identify base composition, the presence of high- and low-mutation clusters and transition/transversion biases as the main factors driving this heterogeneity. Furthermore, we find that mutability correlates with the ability of HCV to diversify in patients. These data provide a site-wise baseline for interrogating natural selection, genetic load and evolvability in HCV, as well as for evaluating drug resistance and immune evasion risks.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Genoma Viral / Hepatite C / Hepacivirus / Taxa de Mutação Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Genoma Viral / Hepatite C / Hepacivirus / Taxa de Mutação Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nat Microbiol Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Espanha