The Fitness Trade-off Between Growth and Stress Resistance Determines the Phenotypic Landscape

Background: A central challenge in biology is to discover a principle that determines individual phenotypic differences within a species. The growth rate is particularly important for a unicellular organism, and the growth rate under a certain condition is negatively associated with that of another condition, termed fitness trade-off. Therefore, there should exist a common molecular mechanism that regulates multiple growth rates under various conditions, but most studies so far have focused on discovering those genes associated with growth rates under a specific condition.

Results: In this study, we found that there exists a recurrent gene expression signature whose expression levels are related to the fitness trade-off between growth preference and stress resistance across various yeast strains and multiple conditions. We further found that the genomic variation of stress-response, ribosomal, and cell cycle regulators are potential causal genes that determine the sensitivity between growth and survival. Intriguingly, we further observed that the same principle holds for human cells using anticancer drug sensitivities across multiple cancer cell lines.

Conclusions: Together, we suggest that the fitness trade-off is an evolutionary trait that determines individual growth phenotype within a species. By using this trait, we can possibly overcome anticancer drug resistance in cancer cells.