Unlocking the hidden dance of cellular resilience

Abstract

Biological systems are dynamic and multi-layered, characterized by internal structures with varying levels of complexity that are in constant interplay. For instance, the regulated interaction between gene expression machinery and the biochemical reactions among proteins is crucial for orchestrating cellular functions. This interplay is essential for maintaining life, even in seemingly "simpler" single-cell organisms, amidst an ever-changing external environment. These interactions create a complex web of connections between different biological organization levels, making studying such systems enormously challenging. However, the story does not end there; biological systems have the remarkable ability to evolve. Evolution is fundamental to all living beings on Earth, enabling the vast diversity of forms, shapes, lifestyles, and colors observed in nature. Anticipating evolutionary outcomes has long perplexed scientists. In some cases, evolution appears to follow reproducible trajectories, providing opportunities to investigate factors that may constrain evolutionary paths while controlling for external environmental in_uences. One such factor, discovered in the past century, is epistasis, which refers to the variable effect of a gene mutation depending on the presence or absence of mutations in other genes. This concept has played a pivotal role in shaping our understanding of evolutionary processes. In this thesis, we examine the effects of epistatic mutations on a genome-wide scale within a speci_c evolutionary trajectory...