This doctoral thesis, supervised by Beatriz Sabater and Ron Geller, with Mario Fares as honorary director, analyses the role of duplicated genes in the phenotypic plasticity of the yeast Saccharomyces cerevisiae and the role of genetic variability in the adaptive capacity of CVB3, an RNA virus. The results of the research have been published in the journals DNA research, G3: Genes, Genomes and Genetics, Environmental Microbiology, mSystems, eLife and Scientific Reports. The thesis was defended on 22 April 2021.
Living organisms are confronted with changing, often stressful, environmental conditions that test their ability to survive. The change in the genetic composition of populations lies in mutations, which are the source of evolution and adaptation to change. This PhD thesis, entitled "Unveiling adaptive mechanisms through experimental evolution: The role of duplicated genes and phenotypic plasticity in yeast, and the genetic variability in Coxsackievirus", seeks to address two fundamental questions in evolutionary biology: What are the molecular mechanisms that determine the stability of duplicated genes in the genome long enough for them to acquire evolutionary relevance? And how does genetic variability contribute to evolution and adaptation to new environments? In order to try to expand our knowledge of evolutionary mechanisms, and given that the effects of evolution in nature take a long time to be observed, we need biological systems that evolve quickly. Therefore, two different experimental models were used in this thesis: the yeast S. cerevisiae and the coxsackievirus B3 (CVB3). In yeast, the level of gene expression of duplicated genes, as well as transcriptional and functional divergence, were found to be critical for the stability of duplicated genes in the genome. Furthermore, transcriptional plasticity of the duplicated genes was found to play a key role in adaptation to new unfavourable environments, such as oxidative stress conditions or high concentrations of ethanol, glycerol or lactic acid. On the other hand, using the CVB3 virus, a deep mutational scanning approach was performed on the viral capsid proteins and viral populations with high genetic variability were generated. With these highly diverse viral populations, we studied how this variability contributes to adaptation against thermal inactivation. The results show that, even in RNA viruses with very high mutation rates, an increase in the genetic diversity of the population at the beginning of experimental evolution accelerates the evolutionary process and facilitates adaptation to the new environment.
Florian Mattenberger's thesis started in the laboratory of Mario Fares at the Institute of Plant Molecular and Cell Biology (IBMCP, UPV-CSIC) and has been completed in the Viral Biology group at I2SysBio, under the supervision of Ron Geller (Ramón y Cajal Researcher) and Beatriz Sabater (CSIC Senior Scientist, IBMCP). During the development of the thesis Florian Mattenberger has enjoyed a contract within the Programme FPI from the Spanish Ministry of Science and Innovation. The examining board was formed by Emilia Matallana (I2SysBio, UV-CSIC), Markus Proft (IBV, CSIC) and Vicente Pallás (IBMCP, UPV-CSIC), who graded the thesis as outstanding.
