Innovating Works

BFU2012-36346

Financiado
EL PAPEL DE LA DUPLICACION GENICA EN LA COMPLEJIDAD DE SISTEMAS BIOLOGICOS: RE-D...
EL PAPEL DE LA DUPLICACION GENICA EN LA COMPLEJIDAD DE SISTEMAS BIOLOGICOS: RE-DIRECCION DE DINAMICAS MUTACIONALES Y ORIGEN DE INNOVACIONES BIOLOGICAS RESEARCHERS HAVE LONG BEEN ENTHRALLED WITH THE IDEA THAT GENE DUPLICATION ORIGINATES NOVEL FUNCTIONS AND ADAPTATIONS. IT IS NOW FIRMLY ASSUMED THAT GENE DUPLICATION IS A MAJOR SOURCE OF EVOLUTIONARY NOVELTIES, IN THE FORM OF NEW G... RESEARCHERS HAVE LONG BEEN ENTHRALLED WITH THE IDEA THAT GENE DUPLICATION ORIGINATES NOVEL FUNCTIONS AND ADAPTATIONS. IT IS NOW FIRMLY ASSUMED THAT GENE DUPLICATION IS A MAJOR SOURCE OF EVOLUTIONARY NOVELTIES, IN THE FORM OF NEW GENES AND FUNCTIONS, CONTRIBUTING THEREBY TO INCREASING THE PHENOTYPIC DIVERSITY AND TO SPECIATION. IN PARTICULAR, DUPLICATION OF ENTIRE GENOMES (POLYPLOIDIZATION) HAS PRECEDED THE EMERGENCE OF THE UNIQUE MORPHOLOGICAL INNOVATIONS OF JAWED VERTEBRATES AND THE EXPLOSION OF DIVERSITY OF LAND PLANTS DURING THE CRETACEOUS ERA. WHETHER GENE DUPLICATION HAS A CAUSAL ROLE IN THE EMERGENCE OF NOVEL ADAPTATIONS AND MORPHOLOGICAL DIVERSIFICATIONS REMAINS LARGELY UNRESOLVED. THEORY PREDICTS THAT THE LIKELIHOOD OF PRESERVING BOTH COPIES AFTER GENE DUPLICATION IS LOW BECAUSE OF THE STOCHASTIC NATURE OF MUTATIONS ACCUMULATING AT THE SECOND GENE COPY. MASKING THE EFFECTS OF DELETERIOUS MUTATIONS BY A SECOND (REDUNDANT) GENE COPY REQUIRES STRINGENT CONDITIONS REGARDING POPULATION SIZES, DYNAMICS AND MUTATION RATES, MAKING IT AN UNIMPORTANT SELECTIVE FORCE IN THE PERSISTENCE OF BOTH GENE COPIES. THE LARGE FRACTION OF SURVIVING GENES IN DUPLICATE IN ANIMALS AND LAND PLANTS POINTS, HOWEVER, TO OTHER, YET UNEXPLORED, FACTORS HAVING A ROLE IN PRESERVING DUPLICATED GENES. ALTHOUGH MANY ATTENTION-GRABBING EXAMPLES OF INNOVATION BY GENE DUPLICATION HAVE BEEN DESCRIBED IN THE LITERATURE, THE SECONDARY MODIFICATION OF DUPLICATES GENES BY MUTATION AND NATURAL SELECTION REMAINS OBSCURE. UNEARTHING THE PATTERNS OF MUTATION AND SELECTION ON DUPLICATED GENES IS CRUCIAL TO UNDERSTAND THE ROLE OF DUPLICATION IN THE EMERGENCE OF NOVEL ADAPTATIONS. IN THIS PROJECT I AIM AT DETERMINING, USING A MULTI-DISCIPLINARY AND SYSTEMS BIOLOGY APPROACH, THE MUTATIONAL DYNAMICS AND ROLE OF GENE AND GENOME DUPLICATION IN THE GENERATION OF NOVEL PROTEIN FUNCTIONAL VARIANTS. TO ADDRESS THIS OBJECTIVE, WE WILL ANSWER TWO MAIN SPECIFIC QUESTIONS: I) WHAT IS THE ROLE OF GENE DUPLICATION IN RE-SHAPING THE FIXATION DYNAMICS OF MUTATIONS? AND II) HOW DO MUTATIONAL ROBUSTNESS BY GENE DUPLICATION ENABLES THE ORIGINATION OF ADAPTATIONS UNDER STRESS CONDITIONS? TO ANSWER THESE QUESTIONS, I WILL FOCUS ON TWO MAIN MODEL ORGANISMS THAT ARE KNOWN TO HAVE UNDERGONE EVENTS OF SMALL SCALE AND WHOLE GENOME DUPLICATIONS: THE BAKER’S YEAST SACCHAROMYCES CEREVISIAE AND THE PLANT ARABIDOPSIS THALIANA. TO THIS END, WE WILL USE COMPUTATIONAL AND EVOLUTIONARY ANALYSES TO UNDERSTAND HOW NATURAL SELECTION HAS DRIVEN THE FIXATION OF FUNCTIONAL VARIANTS AFTER THE DIFFERENT TYPES OF GENE DUPLICATIONS AND WHAT BIOCHEMICAL AND NETWORK-LEVEL FEATURES MAKE GENES PRONE TO FUNCTIONALLY INNOVATE AND GENERATE ADAPTATIONS AFTER DUPLICATION. IN PARTICULAR WE WILL CONDUCT ANALYSES ON THE ROLE OF GENES IN DUPLICATE IN THE SURVIVAL TO STRESS CONDITIONS. AS PART OF AN ONGOING LARGE-SCALE EVOLUTION EXPERIMENT, WE WILL EXPLORE THE ROLE OF DUPLICATED GENES IN THE EMERGENCE OF INNOVATIVE MUTATIONS ACROSS A REAL-TIME EVOLUTION EXPERIMENT UNDER RELAXED AND STRINGENT ENVIRONMENTAL CONDITIONS. BIOINFORMATIC PREDICTIONS WILL BE CONTRASTED WITH EXPERIMENTAL RESULTS. CONCLUSIONS WILL CONTRIBUTE VASTLY TO OUR UNDERSTANDING OF THE ROLE OF DUPLICATION IN THE EMERGENCE OF ADAPTATIONS AND COMPLEXITY IN BIOLOGICAL SYSTEMS AND IN FURTHERING BIOTECHNOLOGICAL DEVELOPMENTS. ver más
01/01/2012
CSIC
138K€
Perfil tecnológico estimado

Línea de financiación: concedida

El organismo AGENCIA ESTATAL DE INVESTIGACIÓN notifico la concesión del proyecto el día 2012-01-01
Presupuesto El presupuesto total del proyecto asciende a 138K€
Líder del proyecto
AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGA... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 2-3 552M