One of the goals of evolutionary biology is to understand the relationship between genotype, phenotype, and fitness. An organism's genes – its genotype – determine its physical and behavioral traits – its phenotype. Phenotypes, in turn, affect the organisms’ chances of survival and reproduction – its fitness. However, mapping the relationships among these three variables is far from easy. Recently researchers have become able to identify many genetic mutations that increase an organism's fitness, but it is more difficult to work out how these mutations affect an organism’s phenotype, and why they are beneficial.
The mutations that help organisms thrive in a particular environment are often limited to a handful of genes that affect similar biological processes. For example, microbes that grow in environments with limited sugar tend to accumulate mutations in genes involved in systems that determine whether to grow fast and carelessly or to be careful in case the sugar is never replenished. It is possible that these mutations all affect the same one or two phenotypes, such as the decision to grow or to hunker down. If this were the case, researchers should be able to easily predict how well these organisms adapt to new environments. However, it is possible that specific mutations affect several phenotypes, but these extra effects remain invisible until the environment changes and these phenotypes are revealed.
To explore this possibility, Kinsler, Geiler-Samerotte, and Petrov obtained hundreds of individual yeast strains that each contained a different mutation that improved the yeast's fitness in a low sugar environment. They placed these strains into similar environments and measured their fitness. The patterns observed were used to build several models that predicted how many phenotypes each mutation must affect to explain the changes in fitness.
Kinsler, Geiler-Samerotte and Petrov found that the model in which only five phenotypes were affected by the mutations was able to predict the fitness of the yeast in low-sugar environments. However, to predict the fitness of the same mutations in environments that were very different, the model had to include eight phenotypes. This suggests that although the mutations that helped yeast do well in the low sugar environment were similar in their benefits in this environment, they were not truly all the same. In fact, some mutations were quite different from the others in terms of their hidden phenotypic effects.
The hidden effects of mutations can be positive or negative. One mutation might cause an organism to die in a new environment, whereas another might allow it to thrive. Understanding how this works has implications not only for evolutionary biology, but also for medical research. Pathogens that cause infection, and cells that cause cancer, often accumulate mutations in small numbers of crucial genes. Understanding how these mutations affect phenotypes that become important as the environment changes – for instance as the cells encounter new challenges as a tumor grows – and whether different mutations have different hidden effects, could improve treatments in the future.