Harmful algal blooms (HABs) caused by the toxin-producing cyanobacteriaMicrocystisspp., can increase water column pH. While the effect(s) of these basified conditions on the bloom formers are a high research priority, how these pH shifts affect other biota remains understudied. Recently, it was shown these high pH levels decrease growth and Si deposition rates in the freshwater diatomFragilaria crotonensisand natural Lake Erie (Canada-US) diatom populations. However, the physiological mechanisms and transcriptional responses of diatoms associated with these observations remain to be documented. Here, we examinedF. crotonensiswith a set of morphological, physiological, and transcriptomic tools to identify cellular responses to high pH. We suggest 2 potential mechanisms that may contribute to morphological and physiological pH effects observed inF. crotonensis. Moreover, we identified a significant upregulation of mobile genetic elements in theF. crotonensisgenome which appear to be an extreme transcriptional response to this abiotic stress to enhance cellular evolution rates–a process we have termed “genomic roulette.” We discuss the ecological and biogeochemical effects high pH conditions impose on fresh waters and suggest a means by which freshwater diatoms such asF. crotonensismay evade high pH stress to survive in a “basified” future.