Biology subjects

Fumasoni, M.

Publications and source records attributed to Fumasoni, M..

5 recordsLinked to original sources

bioRxiv2025

Experimental evolution of cellular miniaturization reveals a mechanism for cell size evolution

Cell volume, a key determinant of physiology, is maintained by cell size homeostasis. Large deviations from typical size are often harmful, yet cell sizes have diverged drastically in evolution. How size homeostasis evolves to support such diversity without impairing cellular function remains unclear. To address this question, we used experimental evolution to select progressively smaller Saccharomyces cerevisiae cells. Over 1,500 generations, we achieved a four-fold modal volume reduction compared to wild type. Despite this reduction, evolved populations maintained robust size homeostasis and relatively high fitness, revealing that substantial decreases in cell volume can occur without severe growth defects. Whole-genome sequencing and genetic perturbations identify mutations in the G1 cyclin Cln3 and the TOR pathway effector Sch9 as major contributors to cell size reduction, with the Greatwall kinase Rim15 signaling cascade further modulating this phenotype. Manipulating these pathways produced a six-fold range in cell size without changes in ploidy, with engineered mutations recapitulating the volumes of evolved lines and loss-of-function mutations yielding enlarged cells. Our results demonstrate the evolutionary plasticity of cell size homeostasis and reveal a putative mechanism for eukaryotic cell size evolution.

cell biology↗

bioRxiv2025

Model-based inference of cell cycle dynamics captures alterations of the DNA replication programme

The cell cycle of eukaryotic cells consists of several processes that must be carefully orchestrated and completed in a timely manner. Alterations in cell cycle dynamics have been linked to the onset of various diseases, underscoring the need for quantitative methods to analyze cell cycle progression. Here, using a combination of high-throughput experimental data and theoretical modeling, we develop RepliFlow, a model-based approach to infer cell cycle dynamics from flow cytometry data of DNA content in asynchronous cell populations. We model the DNA content distribution as the result of both noisy single-cell measurements and the populations age structure. We show that RepliFlow captures not only changes in the length of each cell cycle phase but also alterations in the underlying DNA replication dynamics. RepliFlow is species-agnostic and recapitulates results from more sophisticated analyses based on nucleotide incorporation. Finally, we propose a minimal DNA replication model that enables to derive microscopic insights about origin firing rates and replication fork speed from population-wide DNA content measurements. Our work presents a scalable framework for inferring cell cycle dynamics from flow cytometry data, enabling the characterization of replication program alterations.

systems biology↗

bioRxiv2024

Compensatory Evolution to DNA Replication Stress is Robust to Nutrient Availability

Evolutionary repair refers to the compensatory evolution that follows perturbations in cellular processes. While evolutionary trajectories are often reproducible, other studies suggest they are shaped by genotype-by-environment (GxE) interactions. Here, we test the predictability of evolutionary repair in response to DNA replication stress--a severe perturbation impairing the conserved mechanisms of DNA synthesis, resulting in genetic instability. We conducted high-throughput experimental evolution on Saccharomyces cerevisiae experiencing constitutive replication stress, grown under different glucose availabilities. We found that glucose levels impact the physiology and adaptation rate of replication stress mutants. However, the genetics of adaptation show remarkable robustness across environments. Recurrent mutations collectively recapitulated the fitness of evolved lines and are advantageous across macronutrient availability. We also identified a novel role of the mediator complex of RNA polymerase II in adaptation to replicative stress. Our results highlight the robustness and predictability of evolutionary repair mechanisms to DNA replication stress and provide new insights into the evolutionary aspects of genome stability, with potential implications for understanding cancer development.

evolutionary biology↗

bioRxiv2020

Genome architecture shapes evolutionary adaptation to DNA replication stress

In haploid budding yeast, evolutionary adaptation to constitutive DNA replication stress alters three genome maintenance modules: DNA replication, the DNA damage checkpoint, and sister chromatid cohesion. We asked how these trajectories depend on a populations genome architecture by comparing the adaptation of haploids to that diploids and recombination deficient haploids. In all three genome architectures, adaptation happens within 1000 generations at rates that are linearly correlated with the initial fitness defect of the ancestors. Mutations in individual genes are selected at different frequencies in different architectures, but the benefits these mutations confer are similar in all three architectures, and combinations of these mutations reproduce the fitness gains of evolved populations. Despite the differences in the selected mutations, the evolutionary trajectories target the same three functional modules in all architectures revealing a common evolutionary response to DNA replication stress.

evolutionary biology↗

bioRxiv2019

The evolutionary plasticity of chromosome metabolism allows adaptation to DNA replication stress

Chromosome metabolism is defined by the pathways that collectively maintain the genome, including chromosome replication, repair and segregation. Because aspects of these pathways are conserved, chromosome metabolism is considered resistant to evolutionary change. We used the budding yeast, Saccharomyces cerevisiae, to investigate the evolutionary plasticity of chromosome metabolism. We experimentally evolved cells constitutively experiencing DNA replication stress caused by the absence of Ctf4, a protein that coordinates the activities at replication forks. Parallel populations adapted to replication stress, over 1000 generations, by acquiring multiple, successive mutations. Whole-genome sequencing and testing candidate mutations revealed adaptive changes in three aspects of chromosome metabolism: DNA replication, DNA damage checkpoint and sister chromatid cohesion. Although no gene was mutated in every population, the same pathways were sequentially altered, defining a functionally reproducible evolutionary trajectory. We propose that this evolutionary plasticity of chromosome metabolism has important implications for genome evolution in natural populations and cancer.

evolutionary biology↗