{"id":64895,"date":"2008-02-06T00:00:00","date_gmt":"2008-02-06T00:00:00","guid":{"rendered":""},"modified":"2008-02-06T00:00:00","modified_gmt":"2008-02-06T00:00:00","slug":"calibration-and-application-of-poliovirus-molecular-clocks-for-epidemiologic-and-evolutionary-studies-calibracion-y-aplicacion-de-relojes-moleculares-de-poliovirus-para-estudios-epidemiologicos-y-e","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/microbiologia\/calibration-and-application-of-poliovirus-molecular-clocks-for-epidemiologic-and-evolutionary-studies-calibracion-y-aplicacion-de-relojes-moleculares-de-poliovirus-para-estudios-epidemiologicos-y-e\/","title":{"rendered":"Calibration and application of poliovirus molecular clocks for epidemiologic and evolutionary studies.  [calibracion y aplicaci\u00f3n de relojes moleculares de poliovirus para estudios epidemiologicos y evolutivos]"},"content":{"rendered":"<h2>Tesis doctoral de <strong> Jaume Jorba I Casanovas <\/strong><\/h2>\n<p>Multiple molecular clocks were calibrated from p1\/capsid nucleotide sequences of well-defined lineages of type-1 wild polioviruses (pv) derived from a common imported ancestor. The rate of substitution of total changes (kt), synonymous transitions (as), synonymous transversions (bs), and nonsynonymous substitutions (ka) were estimated from lineages spanning a 10-year period of circulation and a total evolutionary time of -20 years. The estimated k, rate was [(1.03\u00c2\u00b10.08) x 10~2 ] substitutions per site per year (s\/s\/y). The estimated as rate represented a 93% of the total (kt) rate. The estimated bs rate was 10-fold slower [(0.10\u00c2\u00b10.03) x 10&#8243;2] s\/s\/y and the more stochastic ka rate was -30-fold slower. All estimated rates were calculated by linear regression, maximum-likelihood, and bayesian methods. All three methods estimated consistent values for all rates. The molecular clock hypothesis held for all rates, included the protein clock, as analyzed by likelihood ratio tests with the alternative hypothesis of the non-clock model. The rapid accumulation of synonymous transitions leads to saturation due to multiple superimposed substitutions, particularly at third-codon positions. Simulation studies of 3cp sites suggested that as substitutions would fully saturate at -65 years of independent transmission, whereas for bs substitutions saturation would be incomplete at 100 years. The implications for estimating divergence dates from a5 and bs rates were discussed in this dissertation. Finally, application of molecular clocks to cases of vaccine-derived polioviruses (vdpv) in the framework of the ongoing polio eradication activities were also discussed. m\u00faltiples relojes moleculares fueron calibrados a partir de secuencias de nucleotidos de la c\u00e1pside de cepas salvajes de poliovirus tipo 1 derivadas de un acestro com\u00fan importado y que establecieron lineas evolutivas bien definidas. \u00e9stas comprendieron un tiempo total de circulaci\u00f3n de 10 a\u00f1os y un tiempo total evolutivo de unos 20 a\u00f1os. Se estimaron las tasas de substituci\u00f3n de cambios totales (kt), transiciones sin\u00f3nimas (as), transversiones sin\u00f3nimas (b\u00c2\u00a1) y cambios no sin\u00f3nimos (kj. La tasa estimada de k, fue de [(1.03\u00c2\u00b10.08) x 10~2] substituciones por sitio por a\u00f1o (s\/s\/a), y el valor estimado de as comprende un 93% del de kt. La tasa estimada de bs fue de [(0.10\u00c2\u00b10.03) x 10~2] s\/s\/a, un valor ~10 veces menor que el de kt, mientras que la tasa estimada para ka fue -30 veces menor. Las estimaciones se calcularon mediante rectas de regresi\u00f3n y m\u00e9todos de la m\u00e1xima verosimilitud y bayesianos, arrojando todos ellos valores confluyentes. La hip\u00f3tesis del reloj molecular no fue descartada estad\u00edsticamente frente a la hip\u00f3tesis alternativa del modelo sin reloj molecular mediante tests de proporci\u00f3n de probabilidades. La r\u00e1pida acumulaci\u00f3n de transiciones sin\u00f3nimas conlleva saturaci\u00f3n debido a substituciones m\u00faltiples superimpuestas, concretamente en las terceras posiciones del cod\u00f3n (3cp). Mediante estudios de simulaci\u00f3n en 3cp, las substituciones as se saturar\u00edan completamente en 65 a\u00f1os de transmisi\u00f3n independiente mientras que ias substituciones bs no llegar\u00edan a completar saturaci\u00f3n en 100 a\u00f1os. Las implicaciones de dichos resultados en la estima de fechas de divergencia basados en los relojes as y bs se discuten en esta tesis. Finalmente, la aplicaci\u00f3n de relojes moleculares en casos de poliovirus asociado a vacuna (vdpv) en el marco de las actuales actividades de la eradicaci\u00f3n de la polio tambi\u00e9n son discutidos.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Calibration and application of poliovirus molecular clocks for epidemiologic and evolutionary studies.  [calibracion y aplicaci\u00f3n de relojes moleculares de poliovirus para estudios epidemiologicos y evolutivos]<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Calibration and application of poliovirus molecular clocks for epidemiologic and evolutionary studies.  [calibracion y aplicaci\u00f3n de relojes moleculares de poliovirus para estudios epidemiologicos y evolutivos] <\/li>\n<li><strong>Autor:<\/strong>\u00a0 Jaume Jorba I Casanovas <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Barcelona<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 02\/06\/2008<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Olen Kew<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: esteban Domingo <\/li>\n<li>cara Burns (vocal)<\/li>\n<li>angela Dominguez (vocal)<\/li>\n<li>roderic Guig\u00f3 serra (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de Jaume Jorba I Casanovas Multiple molecular clocks were calibrated from p1\/capsid nucleotide sequences of well-defined lineages of 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