Environmental factors like temperature, pressure, and pH partly shaped the evolution of life. As life progressed, new stressors (e.g., poisons and antibiotics) arose as part of an arms race among ...organisms. Here we ask if cells co-opted existing mechanisms to respond to new stressors, or whether new responses evolved de novo. We use a network-clustering approach based purely on phenotypic growth measurements and interactions among the effects of stressors on population growth. We apply this method to two types of stressors-temperature and antibiotics-to discover the extent to which their cellular responses overlap in Escherichia coli. Our clustering reveals that responses to low and high temperatures are clearly separated, and each is grouped with responses to antibiotics that have similar effects to cold or heat, respectively. As further support, we use a library of transcriptional fluorescent reporters to confirm heat-shock and cold-shock genes are induced by antibiotics. We also show strains evolved at high temperatures are more sensitive to antibiotics that mimic the effects of cold. Taken together, our results strongly suggest that temperature stress responses have been co-opted to deal with antibiotic stress.
Understanding how stressors combine to affect population abundances and trajectories is a fundamental ecological problem with increasingly important implications worldwide. Generalisations about ...interactions among stressors are challenging due to different categorisation methods and how stressors vary across species and systems. Here, we propose using a newly introduced framework to analyse data from the last 25 years on ecological stressor interactions, for example combined effects of temperature, salinity and nutrients on population survival and growth. We contrast our results with the most commonly used existing method – analysis of variance (ANOVA) – and show that ANOVA assumptions are often violated and have inherent limitations for detecting interactions. Moreover, we argue that rescaling – examining relative rather than absolute responses – is critical for ensuring that any interaction measure is independent of the strength of single‐stressor effects. In contrast, non‐rescaled measures – like ANOVA – find fewer interactions when single‐stressor effects are weak. After re‐examining 840 two‐stressor combinations, we conclude that antagonism and additivity are the most frequent interaction types, in strong contrast to previous reports that synergy dominates yet supportive of more recent studies that find more antagonism. Consequently, measuring and re‐assessing the frequency of stressor interaction types is imperative for a better understanding of how stressors affect populations.
Understanding how stressors combine to affect population abundances and trajectories is a fundamental ecological problem with increasingly important implications worldwide. Here, we propose using a newly introduced framework to analyze data from the last 25 years on ecological stressor interactions. We find that many studies that were reported as synergies were actually additive or antagonistic.
Prenatal exposure to ethanol induces aberrant tangential migration of corticopetal GABAergic interneurons, and long-term alterations in the form and function of the prefrontal cortex. We have ...hypothesized that interneuronopathy contributes significantly to the pathoetiology of fetal alcohol spectrum disorders (FASD). Activity-dependent tangential migration of GABAergic cortical neurons is driven by depolarizing responses to ambient GABA present in the cortical enclave. We found that ethanol exposure potentiates the depolarizing action of GABA in GABAergic cortical interneurons of the embryonic mouse brain. Pharmacological antagonism of the cotransporter NKCC1 mitigated ethanol-induced potentiation of GABA depolarization and prevented aberrant patterns of tangential migration induced by ethanol in vitro. In a model of FASD, maternal bumetanide treatment prevented interneuronopathy in the prefrontal cortex of ethanol exposed offspring, including deficits in behavioral flexibility. These findings position interneuronopathy as a mechanism of FASD symptomatology, and posit NKCC1 as a pharmacological target for the management of FASD.
Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the ...context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations' resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics.
Phenotypic plasticity plays a critical role in adaptation to novel environments. Behavioural plasticity enables more rapid responses to unfamiliar conditions than evolution by natural selection. ...Urban ecosystems are one such novel environment in which behavioural plasticity has been documented. However, whether such plasticity is adaptive, and if plasticity is convergent among urban populations, is poorly understood. We studied the nesting biology of an 'urban-adapter' species, the dark-eyed junco (
), to understand the role of plasticity in adapting to city life. We examined (i) whether novel nesting behaviours are adaptive, (ii) whether pairs modify nest characteristics in response to prior outcomes, and (iii) whether two urban populations exhibit similar nesting behaviour. We monitored 170 junco nests in urban Los Angeles and compared our results with prior research on 579 nests from urban San Diego. We found that nests placed in ecologically novel locations (off-ground and on artificial surfaces) increased fitness, and that pairs practiced informed re-nesting in site selection. The Los Angeles population more frequently nested off-ground than the San Diego population and exhibited a higher success rate. Our findings suggest that plasticity facilitates adaptation to urban environments, and that the drivers behind novel nesting behaviours are complex and multifaceted.
Interactions among drugs play a critical role in the killing efficacy of multi-drug treatments. Recent advances in theory and experiment for three-drug interactions enable the search for emergent ...interactions—ones not predictable from pairwise interactions. Previous work has shown it is easier to detect synergies and antagonisms among pairwise interactions when a rescaling method is applied to the interaction metric. However, no study has carefully examined whether new types of normalization might be needed for emergence. Here, we propose several rescaling methods for enhancing the classification of the higher order drug interactions based on our conceptual framework. To choose the rescaling that best separates synergism, antagonism and additivity, we conducted bacterial growth experiments in the presence of single, pairwise and triple-drug combinations among 14 antibiotics. We found one of our rescaling methods is far better at distinguishing synergistic and antagonistic emergent interactions than any of the other methods. Using our new method, we find around 50% of emergent interactions are additive, much less than previous reports of greater than 90% additivity. We conclude that higher order emergent interactions are much more common than previously believed, and we argue these findings for drugs suggest that appropriate rescaling is crucial to infer higher order interactions.
Urban-dwelling birds face novel visual cues and soundscapes. To thrive in these challenging environments, individuals must correctly identify and calibrate threats posed by humans and their ...activities. We showed that Dark-eyed juncos (Junco hyemalis) residing in an urban habitat responded differently to the sounds that approaching people and objects make. A person approached juncos simultaneously playing the sounds of object types that normally move at different relative velocities: faster (bicycles), intermediate (skateboards and scooters), or slower (people walking). Juncos responded at significantly greater distances and moved further in relation to what sound cues would normally imply about the velocity of approach. Absolute stimulus volume was not a significant predictor of response across object type. The responses occurred without the presence of visual cues, suggesting that an auditory cue alone and without visual confirmation can produce an appropriate response. Overall, this shows that this population of urban juncos has the ability to respond appropriately to novel anthropogenic sound cues. The question remains as to how universal such abilities are across species, different urban situations, and in natural habitats.
Exposure of the fetus to alcohol (ethanol) via maternal consumption during pregnancy can result in fetal alcohol spectrum disorders (FASD), hallmarked by long-term physical, behavioral, and ...intellectual abnormalities. In our preclinical mouse model of FASD, prenatal ethanol exposure disrupts tangential migration of corticopetal GABAergic interneurons (GINs) in the embryonic medial prefrontal cortex (mPFC). We postulated that ethanol perturbed the normal pattern of tangential migration via enhancing GABA
receptor-mediated membrane depolarization that prevails during embryonic development in GABAergic cortical interneurons. However, beyond this, our understanding of the underlying mechanisms is incomplete. Here, we tested the hypothesis that the ethanol-enhanced depolarization triggers downstream an increase in high-voltage-activated nifedipine-sensitive L-type calcium channel (LTCC) activity and provide evidence implicating calcium dynamics in the signaling scheme underlying the migration of embryonic GINs and its aberrance. Tangentially migrating Nkx2.1
GINs expressed immunoreactivity to Cav1.2, the canonical neuronal isoform of the L-type calcium channel. Prenatal ethanol exposure did not alter its protein expression profile in the embryonic mPFC. However, exposing ethanol concomitantly with the LTCC blocker nifedipine prevented the ethanol-induced aberrant migration both
and
In addition, whole-cell patch clamp recording of LTCCs in GINs migrating in embryonic mPFC slices revealed that acutely applied ethanol potentiated LTCC activity in migrating GINs. Based on evidence reported in the present study, we conclude that calcium is an important intracellular intermediary downstream of GABA
receptor-mediated depolarization in the mechanistic scheme of an ethanol-induced aberrant tangential migration of embryonic GABAergic cortical interneurons.
Colonization of novel environments creates new selection pressures. Sexually selected traits are affected by the physical and social environment and should be especially susceptible to change, but ...this has rarely been studied. In southern California, dark-eyed juncos, (Junco hyemalis) naturally breed in mixed-coniferous temperate forests, typically from 1500 m to 3000 m in elevation. In the early 1980s, a small population became established in a coastal habitat, the University of California, San Diego campus, which has a mild, Mediterranean climate. I show that a sexually and socially selected signaling trait—the amount of white in the tail—has declined by approximately 22% as compared to mountain juncos. I address three main factors that could explain the difference between mountain and coastal juncos: phenotypic plasticity, genetic drift, and selection. Results indicate that the first two can be ruled out as the sole cause of the plumage change, which implies that selection contributed to the genetic differentiation from the mountain population. The estimated rate of evolution is about 0.2 haldanes, comparable with rates of change in systems where individuals have been artificially introduced into new environments (e.g., guppies and Drosophila). This is the first study to demonstrate evolution of a sexually selected trait after only several generations resulting from a natural invasion into a novel environment.
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