ena-STUDY-BOISE STATE UNIVERSITY-02-03-2021-09:36:52:008-1202
Dynamic RNA fitness seascapes of a group I ribozyme during changes to the experimental environment
Fitness landscapes of protein and RNA genes have been studied by experimentally measuring the effects of numerous combinations of mutations. These experimental landscapes have shown that the fitness landscapes of genes are rugged, with multiple peaks, because the effects of individual mutations often change depending on the presence or absence of other mutations. Mutational effects also depend upon the environment. However, most experiments have only studied gene function under a single environmental condition, and the effect of environmental changes on fitness landscapes remains unknown. Here we investigate the dynamic “fitness seascapes” a catalytic RNA molecule while changing a functionally important environmental variable. We mapped a fitness landscape of the Azoarcus group I ribozyme under different concentrations of magnesium ions. We analyzed the changing peaks and valleys in the landscape and used evolutionary simulations to determine how populations of ribozymes competing for survival would navigate the landscapes under constant or changing magnesium concentrations. We found that the sequence of highest activity (global peak) relative to the naturally occurring wild-type ribozyme changes with different magnesium concentrations. In general, sequence with fewer mutational changes relative to wild-type have higher relative activity at lower magenesium concentrations, and sequences with more mutations are only favored at the higher magnesium concentrations. In addition, the global peak becomes showed increasingly higher relative activity with higher magnesium. In general, we found that the ruggedness of the landscapes decreased with increasing magnesium concentration. Evolutionary simulations demonstrated that populations evolving under fluctuating magnesium concentrations have moving targets of optimization which can result in the preservation of sequences that are not optimal in a single magnesium ion concentration. These results support the idea that environmental fluctuations promote the preservation of genetic diversity even when selection pressure remains high. The preservation of RNA diversity may have promoted evolutionary innovations during life's origins, before the emergence or optimization of systems for magnesium homeostasis.
Fitness landscapes of protein and RNA genes have been studied by experimentally measuring the effects of numerous combinations of mutations. These experimental landscapes have shown that the fitness landscapes of genes are rugged, with multiple peaks, because the effects of individual mutations often change depending on the presence or absence of other mutations. Mutational effects also depend upon the environment. However, most experiments have only studied gene function under a single environmental condition, and the effect of environmental changes on fitness landscapes remains unknown. Here we investigate the dynamic “fitness seascapes” a catalytic RNA molecule while changing a functionally important environmental variable. We mapped a fitness landscape of the Azoarcus group I ribozyme under different concentrations of magnesium ions. We analyzed the changing peaks and valleys in the landscape and used evolutionary simulations to determine how populations of ribozymes competing for survival would navigate the landscapes under constant or changing magnesium concentrations. We found that the sequence of highest activity (global peak) relative to the naturally occurring wild-type ribozyme changes with different magnesium concentrations. In general, sequence with fewer mutational changes relative to wild-type have higher relative activity at lower magenesium concentrations, and sequences with more mutations are only favored at the higher magnesium concentrations. In addition, the global peak becomes showed increasingly higher relative activity with higher magnesium. In general, we found that the ruggedness of the landscapes decreased with increasing magnesium concentration. Evolutionary simulations demonstrated that populations evolving under fluctuating magnesium concentrations have moving targets of optimization which can result in the preservation of sequences that are not optimal in a single magnesium ion concentration. These results support the idea that environmental fluctuations promote the preservation of genetic diversity even when selection pressure remains high. The preservation of RNA diversity may have promoted evolutionary innovations during life's origins, before the emergence or optimization of systems for magnesium homeostasis.