Fitness Trade-Offs Determine the Role of the Molecular Chaperonin GroEL in Buffering Mutations

Molecular chaperones fold many proteins and their mutated versions in a cell and can sometimes buffer the phenotypic effect of mutations that affect protein folding. Unanswered questions about this buffering include the nature of its mechanism, its influence on the genetic variation of a population, the fitness trade-offs constraining this mechanism, and its role in expediting evolution. Answering these questions is fundamental to understand the contribution of buffering to increase genetic variation and ecological diversification. Here, we performed experimental evolution, genome resequencing, and computational analyses to determine the trade-offs and evolutionary trajectories of Escherichia coli expressing high levels of the essential chaperonin GroEL. GroEL is abundantly present in bacteria, particularly in bacteria with large loads of deleterious mutations, suggesting its role in mutational buffering. We show that groEL overexpression is costly to large populations evolving in the laboratory, leading to groE expression decline within 66 generations. In contrast, populations evolving under the strong genetic drift characteristic of endosymbiotic bacteria avoid extinction or can be rescued in the presence of abundant GroEL. Genomes resequenced from cells evolved under strong genetic drift exhibited significantly higher tolerance to deleterious mutations at high GroEL levels than at native levels, revealing that GroEL is buffering mutations in these cells. GroEL buffered mutations in a highly diverse set of proteins that interact with the environment, including substrate and ion membrane transporters, hinting at its role in ecological diversification. Our results reveal the fitness trade-offs of mutational buffering and how genetic variation is maintained in population

Programa E-Health ICOnnecta't: un ecosistema para fomentar el bienestar en cáncer a través de la propuesta europea ONCOMMUN

Introducción: A pesar de que los tratamientos psico-oncológicos han demostrado su efectividad en disminuir el malestar emocional y mejorar la calidad de vida de las personas con cáncer, aún existen numerosas barreras que limitan su acceso. La transformación a online de esta atención se plantea como una solución para aumentar la cobertura del servicio y mejorar su coste-utilidad. Objetivo: Crear un ecosistema digital de salud para reducir el impacto del cáncer, aumentando el bienestar y la calidad de vida del ciudadano con cáncer. Método: Programa dirigido a pacientes diagnosticadas de cáncer de mama en fase de supervivencia aguda. Es un programa de atención escalonada dividido en 4 niveles de intervención jerarquizados por complejidad: Nivel 1, cribado y monitorización psicosocial; Nivel 2, Campus: psicoeducación y educación sanitaria; Nivel 3, soporte psicosocial comunitario; y Nivel 4, tratamiento psicoterapéutico grupal. Resultados: En 2019, 259 mujeres fueron incluidas en el programa (39,91% de los nuevos casos de cáncer de mama en los centros participantes). Solo el 3,47% (n = 9) requirió atención clínica especializada (Nivel 4). Conclusión: El programa Iconnecta't adopta un modelo integrado de atención psicosocial en cáncer que se adecúa a las necesidades específicas de los supervivientes. Da solución a algunas de las barreras de la atención sanitaria tradicional, democratizando el acceso a los servicios mediante el uso de tecnologías de uso común en la mayoría de ciudadanos. En un futuro próximo se prevé la implementación progresiva a otras neoplasias, junto con un ensayo clínico controlado y aleatorizado que evaluará su eficacia

Fitness trade-offs determine the role of the molecular chaperonin GroEL in buffering mutations

Molecular chaperones fold many proteins and their mutated versions in a cell and can sometimes buffer the phenotypic effect of mutations that affect protein folding. Unanswered questions about this buffering include the nature of its mechanism, its influence on the genetic variation of a population, the fitness trade-offs constraining this mechanism, and its role in expediting evolution. Answering these questions is fundamental to understand the contribution of buffering to increase genetic variation and ecological diversification. Here, we performed experimental evolution, genome resequencing, and computational analyses to determine the trade-offs and evolutionary trajectories of Escherichia coli expressing high levels of the essential chaperonin GroEL. GroEL is abundantly present in bacteria, particularly in bacteria with large loads of deleterious mutations, suggesting its role in mutational buffering. We show that groEL overexpression is costly to large populations evolving in the laboratory, leading to groE expression decline within 66 generations. In contrast, populations evolving under the strong genetic drift characteristic of endosymbiotic bacteria avoid extinction or can be rescued in the presence of abundant GroEL. Genomes resequenced from cells evolved under strong genetic drift exhibited significantly higher tolerance to deleterious mutations at high GroEL levels than at native levels, revealing that GroEL is buffering mutations in these cells. GroEL buffered mutations in a highly diverse set of proteins that interact with the environment, including substrate and ion membrane transporters, hinting at its role in ecological diversification. Our results reveal the fitness trade-offs of mutational buffering and how genetic variation is maintained in populations