Challenges and potential solutions for studying the genetic and phenotypic architecture of adaptation in microbes

Abstract

All organisms are defined by the makeup of their DNA. Over billions of years, the structure and information contained in that DNA, often referred to as genetic architecture, have been honed by a multitude of evolutionary processes. Mutations that cause genetic elements to change in a way that results in beneficial phenotypic change are more likely to survive and propagate through the population in a process known as adaptation. Recent work reveals that the genetic targets of adaptation are varied and can change with genetic background. Further, seemingly similar adaptive mutations, even within the same gene, can have diverse and unpredictable effects on phenotype. These challenges represent major obstacles in predicting adaptation and evolution. In this review, we cover these concepts in detail and identify three emerging synergistic solutions: higher-throughput evolution experiments combined with updated genotype-phenotype mapping strategies and physiological models. Our review largely focuses on recent literature in yeast, and the field seems to be on the cusp of a new era with regard to studying the predictability of evolution.

Keywords: Adaptation; Epistasis; Evolution; Genotype-Phenotype Map; Pleiotropy; Yeast.

Figure 1.

The problems associated with predicting adaptation. A. problem 1: the genetic targets of adaptation can be numerous and varied. Traditional methods of isolating adaptive mutants from experimental evolutions were often too low-throughput to catch lower frequency adaptive lineages, leading to the hypothesis that selection only targeted a handful of genes in a given context. B. problem 2: the genetic basis of adaptation changes with genetic background. Mutations rarely affect phenotype in a way that is independent of the existing genetic background (dark blue yeasts). Instead, often epistasis leads to unpredictable phenotypes when a new mutation interacts with its genetic context (multicolored yeasts). C. problem 3: seemingly similar adaptive mutants have diverse and unpredictable effects on phenotype. Mutants evolved in a given condition, the “home” environment, have a similar phenotype: increased fitness in the home environment. One might expect them to have an equally uniform response to a new, “non-home”, environment. However, the pleiotropic effects of mutations often make the response to novel conditions discordant and unpredictable.

Figure 2.

Illustrations of concepts described in Strategies 2 and 3. A. genotype-to-phenotype maps. i. a simple bipartite model in which a single phenotype predictably correlates with genotype. ii. a more realistic, complex model in which genotype affects many correlated phenotypes through direct and indirect actions. B. the network effects of mutations. Network models could help explain the pleiotropic and epistatic interactions of mutations. Detailing how genes interact can give us a basis for predicting mutational effects. For example, when a hub gene is hit with a mutation (blue), the effects of that mutation may extend to all of the genes with which it interacts.