Disentangling the effects of genetic architecture, mutational bias and selection on evolutionary forecasting

Predicting evolutionary change posses numerous challenges. Here we take advantage of the model bacterium Pseudomonas fluorescens in which the genotype-to-phenotype map determining evolution of the adaptive wrinkly spreader (WS) type is known. We present mathematical descriptions of three necessary regulatory pathways and use these to predict both the routes that evolution follows and the expected mutational targets. To test predictions, mutation rates and targets were determined for each pathway. Unanticipated mutational hotspots caused data to depart from predictions but the new data were readily incorporated into refined models. A mismatch was observed between the spectra of WS-causing mutations obtained with and without selection due to low fitness of previously undetected WS-causing mutations. Our findings contribute toward the development of mechanistic models for forecasting evolution, highlight current limitations, and draw attention to challenges in predicting locus-specific mutational biases and fitness effects.