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Quentin
FERNANDEZ DE GRADO

Doctorant
Team MAGe
[info]
Address: Bâtiment Taillefer, Allée des Alpes, Domaine de la Merci
Office: 123
Thesis
Subject:"Etude de l'évolution du métabolisme bactérien par modélisation et simulation"

Thesis director (s): Antoine FRENOY

My name is Quentin FERNANDEZ DE GRADO, and I am currently in the second year of my PhD at TIMC, within the MAGe team.

Research themes

My thesis aims to enhance our knowledge of the evolutionary mechanisms impacting an organism's journey toward adaptation. First, we will study the selective pressures that shape the order of genes in operons. Second, we will investigate the evolutionary mechanisms that affect the evolution of a population's mutation rate, and the impact on the genome organization.

Keywords

Microbial evolution / Genome organization / Modeling / Metabolism/ Operon

Teachings

Biostatistics (15 hours): How to choose a statistical test, interpret its results, and use the R statistical software.

Projects

Gene order in operons:

Bacterial genomes are organized in operons, grouping multiple genes that are expressed in similar biological conditions. We study the order of genes within operons, a question that has received little attention. The specific question we ask is whether two genes catalyzing two successive reactions of a metabolic pathway are encoded in the same order within their operon than they appear within the pathway. A pioneer study has shown 15 years ago that the answer is yes for more than half of such gene pairs, and suggested a mechanism leading to a selection pressure for coding genes in this order. On the opposite, in this work we are looking for selection pressures which could explain why a significant amount of gene pairs are encoded in the invert genetic order.

For all metabolic operons of E. coli, we computed several features which could directly or indirectly reflect the benefit of the invert genetic order, such as essentiality of each gene, fitness defect associated with knockout or over-expression of each gene, average expression level of the operon, potential toxicity of the intermediate metabolite between the two reactions, and conservation of the genes in their order in other organisms.

We found that fitness defect caused by knockout of the downstream gene within the pathway is significantly associated with the inverse gene order (in which this downstream gene is encoded first in the operon), suggesting that this inverse order arises from a selection pressure for strong and robust expression of the downstream gene. We postulate that in some pathways, this selection pressure could be caused by the toxicity of the intermediate metabolite, leading to a benefit in stronger and more robust expression of the gene which consumes the metabolite than the gene which produces it.

Mutation rate evolution:

Soon