Experimental Evolution of Anticipatory Regulation in Escherichia coli

Environmental cues in an ecological niche are often temporal in nature. For instance, in temperate climates, temperature is higher in daytime compared to during night. In response to these temporal cues, bacteria have been known to exhibit anticipatory regulation, whereby triggering response to a yet to appear cue. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature of regulatory networks in microorganisms. However, the conditions under which an anticipatory response evolves as an adaptive response are not known. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and predict variables which are likely important for evolution of anticipatory regulatory response. We follow this with experimental evolution of Escherichia coli in alternating environments of rhamnose and paraquat for ∼850 generations. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation. As a result, pre-exposure to rhamnose leads to a greater fitness in paraquat environment. Genome sequencing reveals that this anticipatory regulation is encoded via mutations in global regulators. Overall, our study contributes to understanding of how environment shapes the topology of regulatory networks in an organism.

Prefrontal cortex interactions with the amygdala in primates

This review addresses functional interactions between the primate prefrontal cortex (PFC) and the amygdala, with emphasis on their contributions to behavior and cognition. The interplay between these two telencephalic structures contributes to adaptive behavior and to the evolutionary success of all primate species. In our species, dysfunction in this circuitry creates vulnerabilities to psychopathologies. Here, we describe amygdala–PFC contributions to behaviors that have direct relevance to Darwinian fitness: learned approach and avoidance, foraging, predator defense, and social signaling, which have in common the need for flexibility and sensitivity to specific and rapidly changing contexts. Examples include the prediction of positive outcomes, such as food availability, food desirability, and various social rewards, or of negative outcomes, such as threats of harm from predators or conspecifics. To promote fitness optimally, these stimulus–outcome associations need to be rapidly updated when an associative contingency changes or when the value of a predicted outcome changes. We review evidence from nonhuman primates implicating the PFC, the amygdala, and their functional interactions in these processes, with links to experimental work and clinical findings in humans where possible.

The Accumulating Costs Hypothesis—to Better Understand Delayed “Hidden” Costs of Seemingly Mild Disease and Other Moderate Stressors

Mild diseases and moderate stressors are seemingly harmless and are therefore often assumed to have negligible impact on Darwinian fitness. Here we argue that the effects of “benign” parasites and other moderate stressors may have a greater impact on lifespan and other fitness traits than generally thought. We outline the “accumulating costs” hypothesis which proposes that moderate strains on the body caused by mild diseases and other moderate stressors that occur throughout life will result in small irreversible “somatic lesions” that initially are invisible (i.e., induce “hidden” costs). However, over time these somatic lesions accumulate until their summed effect reaches a critical point when cell senescence and malfunction begin to affect organ functionality and lead to the onset of degenerative diseases and aging. We briefly discuss three potential mechanisms through which the effects of moderate strains (e.g., mild diseases) could accumulate: Accelerated telomere shortening, loss of repetitious cell compartments and other uncorrected DNA damage in the genome. We suggest that telomere shortening may be a key candidate for further research with respect to the accumulating costs hypothesis. Telomeres can acquire lesions from moderate strains without immediate negative effects, lesions can be accumulated over time and lead to a critically short telomere length, which may eventually cause severe somatic malfunctioning, including aging. If effects of mild diseases, benign parasites and moderate stressors accrued throughout life can have severe delayed consequences, this might contribute to our understanding of life history strategies and trade-offs, and have important implications for medicine, including consideration of treatment therapies for mild (chronic) infections such as malaria.

The Plastid-Localized AtFtsHi3 Pseudo-Protease of Arabidopsis thaliana Has an Impact on Plant Growth and Drought Tolerance

While drought severely affects plant growth and crop production, the molecular mechanisms of the drought response of plants remain unclear. In this study, we demonstrated for the first time the effect of the pseudo-protease AtFtsHi3 of Arabidopsis thaliana on overall plant growth and in drought tolerance. An AtFTSHi3 knock-down mutant [ftshi3-1(kd)] displayed a pale-green phenotype with lower photosynthetic efficiency and Darwinian fitness compared to wild type (Wt). An observed delay in seed germination of ftshi3-1(kd) was attributed to overaccumulation of abscisic acid (ABA); ftshi3-1(kd) seedlings showed partial sensitivity to exogenous ABA. Being exposed to similar severity of soil drying, ftshi3-1(kd) was drought-tolerant up to 20 days after the last irrigation, while wild type plants wilted after 12 days. Leaves of ftshi3-1(kd) contained reduced stomata size, density, and a smaller stomatic aperture. During drought stress, ftshi3-1(kd) showed lowered stomatal conductance, increased intrinsic water-use efficiency (WUEi), and slower stress acclimation. Expression levels of ABA-responsive genes were higher in leaves of ftshi3-1(kd) than Wt; DREB1A, but not DREB2A, was significantly upregulated during drought. However, although ftshi3-1(kd) displayed a drought-tolerant phenotype in aboveground tissue, the root-associated bacterial community responded to drought.

Bioenergetics in environmental adaptation and stress tolerance of aquatic ectotherms: linking physiology and ecology in a multi-stressor landscape

ABSTRACT Energy metabolism (encompassing energy assimilation, conversion and utilization) plays a central role in all life processes and serves as a link between the organismal physiology, behavior and ecology. Metabolic rates define the physiological and life-history performance of an organism, have direct implications for Darwinian fitness, and affect ecologically relevant traits such as the trophic relationships, productivity and ecosystem engineering functions. Natural environmental variability and anthropogenic changes expose aquatic ectotherms to multiple stressors that can strongly affect their energy metabolism and thereby modify the energy fluxes within an organism and in the ecosystem. This Review focuses on the role of bioenergetic disturbances and metabolic adjustments in responses to multiple stressors (especially the general cellular stress response), provides examples of the effects of multiple stressors on energy intake, assimilation, conversion and expenditure, and discusses the conceptual and quantitative approaches to identify and mechanistically explain the energy trade-offs in multiple stressor scenarios, and link the cellular and organismal bioenergetics with fitness, productivity and/or ecological functions of aquatic ectotherms.

Determining cancer risk: the evolutionary multistage model or total stem cell divisions?

A recent hypothesis proposed that the total number of stem cell divisions in a tissue (TSCD model) determine its intrinsic cancer risk; however, a different model—the multistage model—has long been used to understand how cancer originates. Identifying the correct model has important implications for interpreting the frequency of cancers. Using worldwide cancer incidence data, we applied three tests to the TSCD model and an evolutionary multistage model of carcinogenesis (EMMC), a model in which cancer suppression is recognized as an evolving trait, with natural selection acting to suppress cancers causing a significant mean loss of Darwinian fitness. Each test supported the EMMC but contradicted the TSCD model. This outcome undermines results based on the TSCD model quantifying the relative importance of ‘bad luck' (the random accumulation of somatic mutations) versus environmental and genetic factors in determining cancer incidence. Our testing supported the EMMC prediction that cancers of large rapidly dividing tissues predominate late in life. Another important prediction is that an indicator of recent oncogenic environmental change is an unusually high mean fitness loss due to cancer, rather than a high lifetime incidence. The evolutionary model also predicts that large and/or long-lived animals have evolved mechanisms of cancer suppression that may be of value in preventing or controlling human cancers.

Obligate mutualistic cooperation limits evolvability

Cooperative mutualisms are widespread in nature and play fundamental roles in many ecosystems. Due to the often obligate nature of these interactions, the Darwinian fitness of the participating individuals is not only determined by the information encoded in their own genomes, but also the traits and capabilities of their corresponding interaction partners. Thus, a major outstanding question is how obligate cooperative mutualisms affect the ability of organisms to respond to environmental change with evolutionary adaptation. Here we address this issue using a mutualistic cooperation between two auxotrophic genotypes of Escherichia coli that reciprocally exchange costly amino acids. Amino acid-supplemented monocultures and unsupplemented cocultures were exposed to stepwise increasing concentrations of different antibiotics. This selection experiment revealed that metabolically interdependent bacteria were generally less able to adapt to environmental stress than autonomously growing strains. Moreover, obligate cooperative mutualists frequently regained metabolic autonomy, thus resulting in a collapse of the mutualistic interaction. Together, our results identify a limited evolvability as a significant evolutionary cost that individuals have to pay when entering into an obligate mutualistic cooperation.

Predicting experimental designs leading to rewiring of transcription program and evolution of anticipatory regulation in E. coli

Environmental cues in an ecological niche are temporal. In response to these temporal cues, bacteria have been known to exhibit learning or conditioning, whereby they trigger response to a yet to appear cue, anticipating its actual arrival in the near future. Such an anticipatory response in known to enhance Darwinian fitness, and hence, is likely an important feature in the regulatory networks in microorganisms. However, the conditions under which an anticipatory response optimizes cellular fitness are not known. Nor has evolution of anticipatory regulation in laboratory conditions been experimentally demonstrated. In this work, we develop a quantitative model to study response of a population to two temporal environmental cues, and present the key variables in cellular physiology associated with response to the cues whose modulation is likely to lead to evolution of anticipatory regulatory response. We predict experimental conditions, which are likely to lead to demonstration of rewiring of regulation, and evolution of anticipatory response in bacterial populations. Using inputs from the modeling results, we evolve E. coli in alternating environments of the pentose sugar rhamnose and paraquat, which induces oxidative stress. We demonstrate that growth in this cyclical environment leads to evolution of anticipatory regulation. Thus, we argue that in niches where environmental stimuli have a cyclical nature, conditioning evolves in a population as an adaptive response.

Social determinants of health and survival in humans and other animals

The social environment, both in early life and adulthood, is one of the strongest predictors of morbidity and mortality risk in humans. Evidence from long-term studies of other social mammals indicates that this relationship is similar across many species. In addition, experimental studies show that social interactions can causally alter animal physiology, disease risk, and life span itself. These findings highlight the importance of the social environment to health and mortality as well as Darwinian fitness—outcomes of interest to social scientists and biologists alike. They thus emphasize the utility of cross-species analysis for understanding the predictors of, and mechanisms underlying, social gradients in health.