Evolutionary adaptation is the process by which organisms change or acquire features over time in response to new challenges. The ability of organisms to adapt is remarkable and is demonstrated by the many examples of species perfectly suited for the environment they live in, such as spectacular cases of mimicry or tolerance to extreme environments.
Years of laboratory experiments with microorganisms have revealed how cells are capable of adapting to new challenges over short evolutionary timescales. However, what dictates which mutations will contribute to a complex adaptation, and what aspect of cell biology they alter, has remained elusive. To investigate these points, Fumasoni and Murray took advantage of a previously characterized adaptation to constitutive DNA replication stress to study how the genomic features of cells affect their evolution.
DNA replication stress is described as a wide variety of insults, either genetic or environmental, that perturb DNA synthesis. Genetic changes that produce replication stress are frequent in cancer. In an earlier study the authors evolved haploid budding yeast cells experiencing constitutive DNA replication stress and showed how the adaptation to this stress was achieved through mutations altering three distinct cellular processes: sister chromatid cohesion, DNA replication and cell cycle progression.
In a new study, the authors exploited the high reproducibility of this laboratory evolution experiment to test the possibility that particular features of the cell’s genomes could alter how they adapt to DNA replication stress. To do this, Fumasoni and Murray applied the same selective pressure (DNA replication stress) to diploids (which carry an extra copy of the genome compared to haploids) and recombination deficient cells (which have difficulties in using recombination between identical DNA sequences to repair DNA damage). Despite concerns that these genomic features will have delayed or impaired cells’ adaptation, the authors found that diploids and cells that lack DNA recombination happened as fast, or faster than in the original haploid cells. Through a combination of genome sequencing and engineering Fumasoni and Murray also showed that the genes mutated, but not the cellular process they contributed to, were different in the strains with different genomic features.
In the new study, published in PLOS Genetics, the authors propose that a universal evolutionary solution to DNA replication stress exist, but that its precise implementation through mutations is ‘decided’ by the genomic features of the cells subjected to the stress. This knowledge increases our understanding of how cells adapt to perturbations in their core machineries, and thus improves our ability to predict similar adaptive processes outside the laboratory, including those that occur in the genesis and evolution of cancer.
Marco Fumasoni, former postdoc in the Murray lab at MCB, is now a group leader at the Instituto Gulbenkian de Ciência, where he continues to investigate the interplay between genome maintenance mechanisms and evolutionary forces in shaping cellular features.
