Abstract
Organisms cope with physiological stressors through acclimatizing mechanisms in the short-term and adaptive mechanisms over evolutionary timescales. During adaptation to an environmental or genetic perturbation, beneficial mutations can generate numerous physiological changes: some will be novel with respect to prior physiological states, while others might either restore acclimatizing responses to a wild-type state, reinforce them further, or leave them unchanged. We examined the interplay of acclimatizing and adaptive responses at the level of global gene expression in Methylobacterium extorquens AM1 engineered with a novel central metabolism. Replacing central metabolism with a distinct, foreign pathway resulted in much slower growth than wild-type. After 600 generations of adaptation, however, eight replicate populations founded from this engineered ancestor had improved up to 2.5-fold. A comparison of global gene expression in wild-type, engineered, and all eight evolved strains revealed that the vast majority of changes during physiological adaptation effectively restored acclimatizing processes to wild-type expression states. On average, 93% of expression perturbations from the engineered strain were restored, with 70% of these occurring in perfect parallel across all eight replicate populations. Novel changes were common but typically restricted to one or a few lineages, and reinforcing changes were quite rare. Despite this, cases in which expression was novel or reinforced in parallel were enriched for loci harboring beneficial mutations. One case of parallel, reinforced changes was the pntAB transhydrogenase that uses NADH to reduce NADP+ to NADPH. We show that PntAB activity was highly correlated with the restoration of NAD(H) and NADP(H) pools perturbed in the engineered strain to wild-type levels, and with improved growth. These results suggest that much of the evolved response to genetic perturbation was a consequence rather than a cause of adaptation and that physiology avoided “reinventing the wheel” by restoring acclimatizing processes to the pre-stressed state.
Highlights
Physiological stressors affect organisms across individual and evolutionary timescales: they invoke in individuals processes that work to restore homeostasis, and become over evolutionary timescales the selective pressures that drive adaptation in populations
Our work examined whether adaptation restores stress responses towards wild-type versus novel physiological states during adaptation by studying a bacterium (Methylobacterium extorquens AM1) that was experimentally engineered and evolved with a novel central metabolism
The engineered strain was much slower and less fit than wild-type, but eight replicate populations evolved for six hundred generations showed substantial improvements
Summary
Physiological stressors affect organisms across individual and evolutionary timescales: they invoke in individuals processes that work to restore homeostasis, and become over evolutionary timescales the selective pressures that drive adaptation in populations. How organisms generate innate and evolved responses to stressors – often termed physiological acclimation (or phenotypic plasticity) and adaptation, respectively – is a driving question today in many different fields of science, from the origins of drug resistance to the effects of global climate change. Whereas acclimatizing responses are generally ‘‘prewired’’ and relatively uniform between individuals of a population, the paths and outcomes of adaptation can be many and varied. There are many potential explanations for this variability - such as the randomness of mutations, escaping drift, epistasis, and clonal interference - all of which can give rise to multiple and sometimes quite disparate evolutionary outcomes [1,2,3,4,5,6,7]; yet, in other instances, adaptation is remarkably parallel between independently-evolved lineages, even down to the genetic level [8,9,10]
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