Evolutionary adaptation after crippling cell polarization follows reproducible trajectories

Cells use the genetic instructions provided by genes in particular combinations called ‘modules’ to perform particular jobs. Very different organisms can share many of the same modules because certain abilities are fundamental to the survival of all cells and so they have been retained over the course of evolution. That said, these modules may not necessarily involve the same genes because it is often possible to achieve the same result using different components. One way to study how those modules can diversify is to deliberately disrupt one of the genes in a module, and observe how the organism and its descendants respond over many generations. Other genes in these organisms may acquire genetic mutations that enable the genes to take on the role of the missing protein. However, the removal of a single component can be detrimental to the survival of the organisms or may affect many different processes. This can make it difficult to understand what is going on. A gene called BEM1 is crucial for yeast cells to establish polarity, that is, to allow the different sides of a cell to become distinct from one another. This activity is essential for the yeast to replicate itself. Previous studies have shown that the BEM1 gene had a different role in other species of fungi, which suggests that yeast may have other genes that previously assumed the role that BEM1 does now. In this study, Laan et al. removed BEM1 from yeast and allowed the population of mutant cells to evolve for a thousand generations. The approach differs from previous studies because Laan et al. deliberately selected for yeast that had acquired multiple genetic mutations that can together almost fully compensate for the loss of BEM1. Initially, the mutant cells grew very slowly, were abnormal in shape and likely to burst open. However, by the end of the experiment, the cells were able to grow almost as well as the original yeast cells had before the gene deletion. Genetic analysis revealed that the deletion of BEM1 triggers the inactivation of other genes that are also involved in the regulation of polarity, which largely restored the ability of the disrupted polarity module to work. This restoration follows a ‘reproducible trajectory’, as the same genes were switched off in the same order in different populations of yeast that were studied at the same time. The work is an example of reproducible evolution, whereby a specific order of changes to gene activity repeatedly enables cells with severe defects in important processes to adapt and restore a gene module, using whatever components they have left. The next challenge will be to understand how the particular roles of important modules affect their adaptability.