Resonant fluctuations of selection pressure exponentially accelerate fitness valley crossing

Two functional protein sequences can sometimes be separated by a fitness valley - a series of low or non-functional intermediate mutations that must be traversed to reach a more optimal or refined function. Time-varying selection pressure modulates evolutionary sampling of such valleys. Yet, how the amplitude and frequency of fluctuating selection influence the rate of protein evolution is poorly understood. Here, we derive a simple equation for the time-dependent probability of crossing a fitness valley as a function of evolutionary parameters: valley width, protein size, mutation rate, and selection pressure. The equation predicts that, under low selection pressure, the valley crossing rate is magnified by a factor that depends exponentially on valley width. However, after a characteristic time set by the evolutionary parameters, the rate rapidly decays. Thus, there is an optimal frequency of selection-pressure fluctuations that maximizes the rate of protein optimization. This result is reminiscent of the resonance frequency in mechanical systems. The equation unites empirical and theoretical results that were previously disconnected, and is consistent with time-dependent in vitro and clinical data. More generally, these results suggest that seasonal and climate oscillations could synchronously drive protein evolution at the resonant frequency across a range of organism hosts and timescales. This theory could also be applied to optimize de novo protein evolution in laboratory directed evolution using time-varying protocols.

Gut mélange à trois: fluctuating selection modulated by microbiota, host immune system, and antibiotics

Iron is critical in host-microbe interactions, and its availability is under tight regulation in the mammalian gut. Antibiotics and inflammation are known to perturb iron availability in the gut, which could subsequently alter host-microbe interactions. Here, we show that an adaptive allele of iscR, encoding a major regulator of iron homeostasis of Escherichia coli, is under fluctuating selection in the mouse gut. In vivo competitions in immune-competent, immune-compromised, and germ-free mice reveal that the selective pressure on an iscR mutant E. coli is modulated by the presence of antibiotics, other members of the microbiota, and the immune system. In vitro assays show that iron availability is an important mediator of the iscR allele fitness benefits or costs. We identify Lipocalin-2, a host's innate immune system protein that prevents bacterial iron acquisition, as a major host mechanism underlying fluctuating selection of the iscR allele. Our results provide a remarkable example of strong fluctuating selection acting on bacterial iron regulation in the mammalian gut.

Associations between metabolic traits and growth rate in brown trout ( Salmo trutta ) depend on thermal regime

Metabolism defines the energetic cost of life, yet we still know relatively little about why intraspecific variation in metabolic rate arises and persists. Spatio-temporal variation in selection potentially maintains differences, but relationships between metabolic traits (standard metabolic rate (SMR), maximum metabolic rate (MMR), and aerobic scope) and fitness across contexts are unresolved. We show that associations between SMR, MMR, and growth rate (a key fitness-related trait) vary depending on the thermal regime (a potential selective agent) in offspring of wild-sampled brown trout from two populations reared for approximately 15 months in either a cool or warm (+1.8°C) regime. SMR was positively related to growth in the cool, but negatively related in the warm regime. The opposite patterns were found for MMR and growth associations (positive in warm, negative in the cool regime). Mean SMR, but not MMR, was lower in warm regimes within both populations (i.e. basal metabolic costs were reduced at higher temperatures), consistent with an adaptive acclimation response that optimizes growth. Metabolic phenotypes thus exhibited a thermally sensitive metabolic ‘floor’ and a less flexible metabolic ‘ceiling’. Our findings suggest a role for growth-related fluctuating selection in shaping patterns of metabolic variation that is likely important in adapting to climate change.

Transitional genomes and nutritional role reversals identified for dual symbionts of adelgids (Aphidoidea: Adelgidae)

Many plant-sap-feeding insects have maintained a single, obligate, nutritional symbiont over the long history of their lineage. This senior symbiont may be joined by one or more junior symbionts that compensate for gaps in function incurred through genome-degradative forces. Adelgids are sap-sucking insects that feed solely on conifer trees and follow complex life cycles in which the diet fluctuates in nutrient levels. Adelgids are unusual in that both senior and junior symbionts appear to have been replaced repeatedly over their evolutionary history. Genomes can provide clues to understanding symbiont replacements, but only the dual symbionts of hemlock adelgids have been examined thus far. Here, we sequence and compare genomes of four additional dual-symbiont pairs in adelgids. We show that these symbionts are nutritional partners originating from diverse bacterial lineages and exhibiting wide variation in general genome characteristics. Although dual symbionts cooperate to produce nutrients, the balance of contributions varies widely across pairs, and total genome contents reflect a range of ages and degrees of degradation. Most symbionts appear to be in transitional states of genome reduction. Our findings support a hypothesis of periodic symbiont turnover driven by fluctuating selection for nutritional provisioning related to gains and losses of complex life cycles in their hosts.

Fluctuating selection and global change: a synthesis and review on disentangling the roles of climate amplitude, predictability and novelty

A formidable challenge for global change biologists is to predict how natural populations will respond to the emergence of conditions not observed at present, termed novel climates. Popular approaches to predict population vulnerability are based on the expected degree of novelty relative to the amplitude of historical climate fluctuations experienced by a population. Here, we argue that predictions focused on amplitude may be inaccurate because they ignore the predictability of environmental fluctuations in driving patterns of evolution and responses to climate change. To address this disconnect, we review major findings of evolutionary theory demonstrating the conditions under which phenotypic plasticity is likely to evolve in natural populations, and how plasticity decreases population vulnerability to novel environments. We outline key criteria that experimental studies should aim for to effectively test theoretical predictions, while controlling for the degree of climate novelty. We show that such targeted tests of evolutionary theory are rare, with marine systems being overall underrepresented in this venture despite exhibiting unique opportunities to test theory. We conclude that with more robust experimental designs that manipulate both the amplitude and predictability of fluctuations, while controlling for the degree of novelty, we may better predict population vulnerability to climate change.

Borrelia Infection in Bank Voles Myodes glareolus Is Associated With Specific DQB Haplotypes Which Affect Allelic Divergence Within Individuals

The high polymorphism of Major Histocompatibility Complex (MHC) genes is generally considered to be a result of pathogen-mediated balancing selection. Such selection may operate in the form of heterozygote advantage, and/or through specific MHC allele–pathogen interactions. Specific MHC allele–pathogen interactions may promote polymorphism via negative frequency-dependent selection (NFDS), or selection that varies in time and/or space because of variability in the composition of the pathogen community (fluctuating selection; FS). In addition, divergent allele advantage (DAA) may act on top of these forms of balancing selection, explaining the high sequence divergence between MHC alleles. DAA has primarily been thought of as an extension of heterozygote advantage. However, DAA could also work in concert with NFDS though this is yet to be tested explicitly. To evaluate the importance of DAA in pathogen-mediated balancing selection, we surveyed allelic polymorphism of MHC class II DQB genes in wild bank voles (Myodes glareolus) and tested for associations between DQB haplotypes and infection by Borrelia afzelii, a tick-transmitted bacterium causing Lyme disease in humans. We found two significant associations between DQB haplotypes and infection status: one haplotype was associated with lower risk of infection (resistance), while another was associated with higher risk of infection (susceptibility). Interestingly, allelic divergence within individuals was higher for voles with the resistance haplotype compared to other voles. In contrast, allelic divergence was lower for voles with the susceptibility haplotype than other voles. The pattern of higher allelic divergence in individuals with the resistance haplotype is consistent with NFDS favouring divergent alleles in a natural population, hence selection where DAA works in concert with NFDS.

Annual climatic fluctuations and short-term genetic variation in the eastern spadefoot toad

In addition to variations on the spatial scale, short- and long-term temporal variations, too, can impose intense selection on the overall genetic diversity and composition of a population. We hypothesized that the allelic composition in populations of the eastern spadefoot toad (Pelobates syriacus) would change among successive years in accordance with the short-term changes in environmental conditions. Surprisingly, the effect of short-term climate fluctuations on genetic composition have rarely been addressed in the literature, and to our knowledge the effect of annual climatic fluctuations have not been considered meaningful. Our findings show that climatic variation among successive years, primarily the amount of rainfall and rainy days, can significantly alter both microsatellite allelic composition and diversity. We suggest that environmental (i.e. fluctuating) selection is differential across the globe, and that its intensity is expected to be greatest in regions where short-term climatic conditions are least stable.

Broad geographic sampling reveals the shared basis and environmental correlates of seasonal adaptation in Drosophila

To advance our understanding of adaptation to temporally varying selection pressures, we identified signatures of seasonal adaptation occurring in parallel among Drosophila melanogaster populations. Specifically, we estimated allele frequencies genome-wide from flies sampled early and late in the growing season from 20 widely dispersed populations. We identified parallel seasonal allele frequency shifts across North America and Europe, demonstrating that seasonal adaptation is a general phenomenon of temperate fly populations. Seasonally fluctuating polymorphisms are enriched in large chromosomal inversions and we find a broad concordance between seasonal and spatial allele frequency change. The direction of allele frequency change at seasonally variable polymorphisms can be predicted by weather conditions in the weeks prior to sampling, linking the environment and the genomic response to selection. Our results suggest that fluctuating selection is an important evolutionary force affecting patterns of genetic variation in Drosophila.

Episodes of opposing survival and reproductive selection cause strong fluctuating selection on seasonal migration versus residence

Quantifying temporal variation in sex-specific selection on key ecologically relevant traits, and quantifying how such variation arises through synergistic or opposing components of survival and reproductive selection, is central to understanding eco-evolutionary dynamics, but rarely achieved. Seasonal migration versus residence is one key trait that directly shapes spatio-seasonal population dynamics in spatially and temporally varying environments, but temporal dynamics of sex-specific selection have not been fully quantified. We fitted multi-event capture–recapture models to year-round ring resightings and breeding success data from partially migratory European shags ( Phalacrocorax aristotelis ) to quantify temporal variation in annual sex-specific selection on seasonal migration versus residence arising through adult survival, reproduction and the combination of both (i.e. annual fitness). We demonstrate episodes of strong and strongly fluctuating selection through annual fitness that were broadly synchronized across females and males. These overall fluctuations arose because strong reproductive selection against migration in several years contrasted with strong survival selection against residence in years with extreme climatic events. These results indicate how substantial phenotypic and genetic variation in migration versus residence could be maintained, and highlight that biologically important fluctuations in selection may not be detected unless both survival selection and reproductive selection are appropriately quantified and combined.