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Quantifying the evolutionary potential for Delta Smelt persistence in a warming habitat.

Long-term persistence of managed species will depend, in part, on whether the species harbors the physiological or genetic potential to adjust to warming temperatures, and whether relevant genetic variation is modified by management practices. The critically endangered Delta Smelt (Hypomesus transpacificus) is intensively managed, but little is known about the presence of genetic variation for resistance to elevated temperature, which will be important to maintain for their persistence in a rapidly warming future. Using a pedigree and whole genome sequencing data, we characterized the genetic variation and genomic architecture for CTMax (as a metric of upper thermal tolerance) across control and elevated rearing temperatures, alongside covarying traits (body size, degree of hatchery ancestry). Warmer rearing temperatures increased CTMax through acclimation but also resulted in reduced additive genetic variation for the trait, which could constrain adaptation under thermal stress. We found that larger fish had reduced CTMax, although this effect was diminished at elevated temperatures. We observed modest heritability for CTMax at rearing temperatures of 15°C and 18°C (0.26 and 0.16, respectively), but only a limited number of loci were identified that had consistent effects on CTMax across rearing temperatures. Instead, the genomic basis of thermal tolerance was highly dependent on rearing temperature (many loci detected with a GxE effect). The influence of domestication selection was indicated by changes in allele frequency, and divergence in upper thermal tolerance and plasticity, between low and high hatchery ancestry groups. Minimal overlap between loci associated with domestication and CTMax suggests that these traits possess separate genetic underpinnings. Knowledge of genetic variation supporting ecologically relevant physiological variation may be useful for refuge management and may inform supplementation in an ever-warming environment.

conservation physiology

Quantifying the Evolutionary Potential for Delta Smelt Persistence in a Warming Habitat.

Long-term persistence of managed species will depend, in part, on whether the species harbors the physiological or genetic potential to adjust to warming temperatures, and whether relevant genetic variation is modified by management practices. The critically endangered Delta Smelt (Hypomesus transpacificus) is intensively managed, but little is known about the presence of genetic variation for resistance to elevated temperature. Using a pedigree and whole genome sequencing data, we characterized the genetic basis of CTMax (as a metric of upper thermal tolerance) across control and elevated rearing temperatures, alongside covarying traits (body size and degree of hatchery ancestry). Warmer rearing temperatures increased CTMax through acclimation but also resulted in reduced additive genetic variation for the trait. We observed modest heritability for CTMax at rearing temperatures of 15°C and 18°C (0.26 and 0.16, respectively), but only a limited number of loci were identified that had consistent effects on CTMax across rearing temperatures. Instead, the genomic basis of thermal tolerance was highly dependent on rearing temperature (i.e., many loci detected with a GxE effect). This temperature-dependent genomic architecture is consistent with our finding that additive genetic variation for CTMax was reduced under warmer rearing conditions, indicating a potential constraint on adaptive evolutionary change. The influence of domestication selection was indicated by changes in allele frequency, and divergence in upper thermal tolerance and plasticity, between low and high hatchery ancestry groups. Minimal overlap between loci associated with domestication and CTMax suggests that these traits possess separate genetic underpinnings. Knowledge of genetic variation supporting ecologically relevant physiological variation may be useful for captive management and may inform supplementation of fish to the wild in an ever-warming environment.

conservation physiology

Renal conservation of ketone bodies during starvation.

Renal handling of acetoacetate and beta-hydroxybutyrate was studied in 12 obese subjects undergoing total starvation. Simultaneously, the acetoacetate, beta-hydroxybutyrate, and inulin clearance rates were measured, and acetoacetate and beta-hydroxybutyrate reabsorption rates were calculated. Renal clearance of blood acetoacetate and beta-hydroxybutyrate remained constant. In contrast, acetoacetate reabsorption rate increased significantly from 47 plus or minus 10 mumoles/min on day 3 to 106 plus or minus 15, 89 plus or minus 10, and 96 plus or minus 10 mumoles/min on days 10, 17, and 24, respectively. Similarly, beta-hydroxybutyrate reabsorption rate increased significantly from 154 plus or minus 27 mumoles/min on day 3 to 419 plus or minus 53, 399 plus or minus 25, and 436 plus or minus 53 mumoles/min on days 10, 17, and 24, respectively. Both acetoacetate and beta-hydroxybutyrate reabsorption rates increased linearly when plotted against their filtered loads. Thus, no tubular maximal transport rate exists for acetoacetate or beta-hydroxybutyrate during physiologic ketonemia. Conservation 450-500 mmoles of ketone bodies/day prevents large urinary losses of cations during prolonged starvation. Since ammonium becomes the major cation excreted during prolonged fasting, the increased renal reabsorption of ketone bodies minimizes body protein loss and aids in maintaining high circulating acetoacetate and beta-hydroxybutyrate concentrations.

Acetoacetates

Bradycardia during human diving.

The bradycardial response to the diving reflex, which occurs in man and in diving animals, is thought to be a physiologically protective oxygen-conserving mechanism whereby the animal is kept alive during submergence. The physiology and nervous pathways are not yet fully understood, but several investigators have pointed out the potentially fatal outcome of an accentuated diving reflex. the CO2 content of the peripheral venous blood has been proved variable and unpredictable during the hyperventilation-breath-hold dive cycle in man. A group of 8 male divers (average age 34 years) was investigated during breathhold dives to 3,3 m in a swimming pool. Heart rates were recorded and compared at various stages during breath-hold and SCUBA (self-contained underwater breathing apparatus) dives, viz. when resting on the surface, breath-holding, hyperventilating and swimming underwater. Two divers performed extreme breathhold endurance tests lasting 135 seconds underwater. All divers had a tachycardia after hyperventilation and a bradycardia after breathhold diving, lasting 80-100 seconds. Extrasystoles were recorded during some of the breathhold dives. Prolonged submergence caused extreme bradycardia (24/min) with central cyanosis. Bradycardia during diving may be a physiological )2-conserving reflex or the start of a pathophysiological asphyxial response.

Adult

Phylogenetic Constraints and Environmental Filtering Jointly Drive Adaptive Evolution in Phragmites australis: From Genetic Structure to Trait Decoupling on the Mongolian Plateau.

The Mongolian Plateau, a typical arid and semi-arid zone in Eurasia, is characterized by highly heterogeneous and fragmented wetland habitats. Phragmites australis, a common wetland species in this region, exhibits remarkable adaptability. Unraveling the coordination between phylogenetic history and local environmental filtering is crucial for elucidating its adaptive mechanisms. Integrating landscape genomics and trait-based phylogenetic analyses, we analyzed transcriptome-wide SNPs, multidimensional functional traits, and environmental variables across 90 individuals from 30 natural P. australis populations. This study aims to reveal the genetic and phenotypic variation patterns underlying population genetic structure and trait variation, specifically distinguishing the roles of geographic isolation, environmental filtering, and phylogenetic history. Results reveal a significant drainage-dependent pattern in genetic structure. Populations in hydrologically connected basins show extensive admixture, whereas those in isolated endorheic basins form distinct lineages. While geographic isolation underpins genetic differentiation, environmental filtering independently explains ~33.84% of the genetic variation, driven primarily by moisture heterogeneity (precipitation seasonality and soil moisture). Crucially, we observed differentiated evolutionary trajectories across functional traits. Structural traits (e.g., plant height, leaf thickness) are phylogenetically conserved; in contrast, physiological traits (e.g., water use efficiency) are decoupled from phylogeny, showing patterns consistent with high plasticity regulated by local environments. This evolutionary decoupling strategy enables P. australis to flexibly adapt to heterogeneous habitats while maintaining structural stability. This study uncovers the synergistic mechanisms by which geographic isolation and environmental filtering jointly shape the genetic patterns of this cosmopolitan species at a regional scale, clarifies that its evolutionary responses may depend heavily on the differentiated plasticity of trait types, and provides valuable regional insights into how widespread wetland species adapt to heterogeneous environments under global change.

Mongolia Plateau

Genomic-Environmental Integration Predicts Climate Vulnerability and Adaptive Potential of Tibetan Plateau Herpetofauna.

The herpetofauna of the Tibetan Plateau, home to Earth's highest-elevation ectothermic vertebrates, face escalating threats from rapid climate change. However, conventional conservation strategies often overlook intraspecific genetic variation and adaptive potential, limiting their predictive accuracy and effectiveness. Here, we integrate whole-genome resequencing data with environmental modeling to assess climate vulnerability in two endemic species: Nanorana parkeri (Tibetan frog) and Thermophis baileyi (hot-spring snake). Results suggest that the western populations of the two species exhibit higher genomic offsets under future climate, while some eastern populations of the Tibetan frog face a decrease in niche suitability, and the hot-spring snake will experience varying degrees of loss of suitable habitats. Furthermore, heterozygosity, genetic diversity, and genetic load demonstrate significant correlations with genomic offsets, suggesting that low genetic diversity and high genetic load may weaken the potential to adapt to environmental changes. Based on a genome-niche index that combines genomic offsets with niche suitability change, we identified evolutionary rescue populations that are potentially tolerant to climate change. Our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive potential and enable effective conservation management of high-altitude herpetofauna under rapid climate change.

Animals

The Health Benefits of Exercise: Molecular and Cellular Mechanisms.

Exercise is a low-cost lifestyle intervention that can prevent and alleviate various diseases. It is a potent physiological stimulus that activates conserved molecular signaling pathways. Through the coordinated integration of multiple molecules, pathways, and systems, it leads to systemic health benefits. However, most studies focus on individual systems or molecular mechanisms, lacking systematic integration of the cross-system regulation induced by exercise. We summarize the molecular mechanisms of exercise in the musculoskeletal, cardiovascular, nervous systems, among others. Exercise induces the release of exerkines (e.g., irisin, interleukin-6, and brain-derived neurotrophic factor) and extracellular vesicles, which activate key signaling pathways to enhance mitochondrial function, metabolism and physiological adaptation, while suppressing inflammation and oxidative stress, thereby alleviating diseases and delaying aging through cross-system coordination. We further explore exercise-induced adaptive regulation in extreme environments, including microgravity, hyperbaria, and hypoxia, offering a multifaceted perspective on organismal health regulation. Finally, we outline the prospects and challenges of multiomics, artificial intelligence-driven precision medicine, personalized exercise prescriptions, and exercise mimetics. Overall, this review provides a more integrated perspective on the molecular basis of exercise and offers directions for future mechanistic and translational studies.

exercise

Evolutionary Reorganization of Transcriptomic Architecture Across a UVB Tolerance Gradient in Fish.

Environmental stressors such as ultraviolet radiation impose strong selective pressures on organisms, yet how adaptation to such stressors shapes transcriptomic responses at the network level remains poorly understood. Although stratospheric ozone is recovering globally, substantial regional variation in UV exposure persists, particularly in high-altitude environments where extreme UV levels can occur. Here, we compared three fish models representing distinct biological responses to UVB exposure: wild-type zebrafish (Danio rerio), a melanin-deficient zebrafish mutant (nacre) lacking a major protective mechanism against UVB damage, and the high-altitude Andean killifish Orestias ascotanensis, a species naturally exposed to extreme UVB radiation. Together, these models define a gradient spanning physiological protection, impaired protection, and evolutionary adaptation to UVB stress. Using RNA-seq and protein-protein interaction networks, we show that transcriptomic responses differ markedly across this gradient. Wild-type and nacre zebrafish exhibited relatively limited transcriptomic changes (∼2%-2.4% of genes changing), whereas O. ascotanensis displayed a large-scale and highly coordinated response (∼21.6% of genes changing) characterized by functionally specialized networks enriched in DNA repair pathways. These differences involved not only transcriptomic magnitude but also marked reorganization of transcriptomic architecture. Integration with positive selection analyses revealed that positively selected genes were concentrated within highly interconnected regions of transcriptomic networks, consistent with adaptation involving network reorganization. Furthermore, ortholog-based analyses suggest that adaptive responses involve differential reorganization of a conserved functional background. Together, our results support a model in which adaptation to environmental stress is associated with the reorganization of conserved transcriptomic networks across physiological and evolutionary contexts, providing a systems-level perspective on the molecular basis of adaptation.

UVB radiation

A network of steroid receptor transcription factors regulates ovarian chromatin remodeling in the transition to ovulation.

Steroid receptors are transcription factors activated by progesterone, androgen, and glucocorticoid that bind the same canonical DNA sequence to modulate genome function in response to steroid hormones. However, the mechanisms defining unique physiological roles of these conserved receptors within the same tissue context, including the ovary, remain elusive. Here, we describe the dynamic association between each steroid receptor cistrome in the mouse ovary responding to the hormonal switch from follicle development to ovulation and generate chromatin conformation maps to define steroid receptor roles in promoter-enhancer interactions and gene transcription. Ovulatory hormones trigger progesterone receptor (PGR) and glucocorticoid receptor (NR3C1 [also known as GR]) binding to novel chromatin sites, promoting transcriptional activation of genes that are required for ovulation, whereas AR-chromatin interactions and androgen receptor (AR)-associated genes are repressed. Integration of genomic and transcriptomic data illustrates two parallel modes of PGR-mediated gene activation. Unique cooperation between PGR and GR enables their recruitment to previously inaccessible promoters, increasing histone acetylation, chromatin accessibility, and transcription activation, with PGR being the indispensable component of this transcriptional complex. Alternatively, PGR tethered to enhancers interacting with preaccessible, AR/GR-bound promoters induces gene activation. Our findings illustrate the multifaceted steroid receptor interactions that translate progressive change in steroid environments to collectively reprogram granulosa cell genome function to switch from follicle development to ovulation.

Journal Article

Renal function changes during preoptic-anterior hypothalamic heating in the rabbit.

Thermoregulatory reactions evoked by selective preoptic-anterior hypothalamic (PO/AH) heating in conscious rabbits were associated with significant changes in renal function. Urine flow rate decreased from a control value of 0.92 +/- (S.E.) 0.08 to 0.47 +/- 0.07 ml/min after 10-20 min of heating, urine osmolality increased from 273 +/- 34 to 417 +/- 46 Osm/kg H2O, and free water clearance per 100 ml GFR decreased from 1.11 +/- 0.46 to -0.50 +/- 0.23 ml/min. These changes were followed by a gradual recovery despite continued heating. Clearances of exogenous creatinine and p-aminohippurate fell transiently during the first 10 min of heating and then returned to normal. Plasma antidiuretic activity (ADA) measured by rat bioassay increased regularly and markedly during PO/AH heating but was poorly correlated with changes in urine concentration. Moreover, a similar increase in plasma ADA observed with selective heating of a different brain area (supraoptic nucleus) never produced urine concentration or other renal changes. This suggests that a large and variable fraction of ADA appearing in rabbit blood in response to thermal stimuli was not identical with antidiuretic hormone. Therefore, the causal relationship of ADH release and antidiuresis associated with thermoregulatory reactions could not be clearly demonstrated. The physiological role of renal water conservation would be to compensate for extrarenal water loss related to thermal sweating or panting.

Animals

Recent Adaptation in a Threatened Salmonid Revealed by Museum Genomics.

Steelhead/rainbow trout (Oncorhynchus mykiss) is an imperilled salmonid with two main life history strategies: migrate to the ocean or remain in freshwater. Domesticated hatchery forms of this species have been stocked into almost all California waterways, possibly resulting in introgression into natural populations and altered population structure. We compared whole-genome sequence data from contemporary populations against a set of museum population samples of steelhead from the same locations that were collected prior to most hatchery stocking. We observed minimal introgression and few steelhead-hatchery trout hybrids despite a century of extensive stocking. Our historical data show signals of introgression with a sister species and indications of an early hatchery facility. Finally, we found that migration-associated haplotypes have become less frequent over time, a likely adaptation to decreased opportunities for migration. Since contemporary migration-associated haplotype frequencies have been used to guide species management, we consider this to be a rare example of shifting baseline syndrome that has been validated with historical data. We suggest cautious optimism that a century of hatchery stocking has had minimal impact on California steelhead population genetic structure, but we note that continued shifts in life history may lead to further declines in the ocean-going form of the species.

Animals

Genotype by Environment Interactions in Gene Regulation Underlie the Response to Soil Drying in the Model Grass Brachypodium distachyon.

Gene expression is a quantitative trait under the control of genetic and environmental factors and their interaction, so-called genotype and environment (G × E). Understanding the mechanisms driving G × E is fundamental for ensuring stable crop performance across environments and for predicting the response of natural populations to climate change. Gene expression is regulated through complex molecular networks, yet the interactions between genotype and environment in gene regulation are rarely considered, particularly at the genome scale. Current frameworks and experimental designs often lack power to explicitly test network rewiring or to systematically compare regulatory networks. Here, we leverage a highly replicated RNA-sequencing dataset to model genome-scale gene expression variation between two natural accessions of the model grass Brachypodium distachyon and their response to soil drying. We first identified genotypic, environmental, and G × E effects on physiological, metabolic, and gene expression traits. We identify patterns of conservation-or variation-in gene coexpression networks and link these coexpression features to physiological traits. We further develop predictions of gene-gene interactions using causal inference and screen for interactions specific to-or with higher affinity in-a single genotype, treatment, or their interaction, G × E. Our analyses identify variation in candidate gene regulatory networks that may shape the evolution of environmental response in B. distachyon. We highlight the environmentally dependent regulatory control of several metabolic traits shown previously to play a role in drought acclimation. The framework presented here provides a scalable approach for more complex comparisons, particularly with the growing availability of large datasets from technologies such as single-cell transcriptomics.

Brachypodium

Harnessing Landscape Genomics to Evaluate Genomic Vulnerability and Future Climate Resilience in an East Asia Perennial.

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions and bolstering shaping species-specific germplasm conservation strategies. We primarily employed landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 201 individuals across 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation. The species complex exhibited strong signatures of local adaptation and differential genomic vulnerabilities across its distribution range, with eastern lineage populations facing significant maladaptation risks under future climate scenarios. Using diverse datasets of putatively adaptive loci and climate change scenarios, we delineated three distinct seed zones within the species' range, estimated varying sample sizes per zone to capture most adaptive diversity, and predicted shifts in seed zone centroids ranging from 48.3 to 359.3 km from historical distributions to mitigate climate change impacts. Collectively, our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive trajectory of an East Asian perennial under anticipated climate changes, guide seed zone delineation for germplasm conservation and enhance population resilience. These results provide a blueprint for designing targeted conservation strategies and restoration plans in other imperilled species.

Climate Change

Ypel5 regulates liver development and function in zebrafish.

YPEL5 is a member of the Yippee-like (YPEL) gene family that is evolutionarily conserved in eukaryotic species. To date, the physiological function of YPEL5 has not been assessed due to a paucity of genetic animal models. Here, using CRISPR/Cas9-mediated genome editing, we generated a stable ypel5-/- mutant zebrafish line. Disruption of ypel5 expression leads to liver enlargement associated with hepatic cell proliferation. Meanwhile, hepatic metabolism and function are dysregulated in ypel5-/- mutant zebrafish, as revealed by metabolomic and transcriptomic analyses. Mechanistically, Hnf4a is identified as a crucial downstream mediator that is positively regulated by Ypel5. Zebrafish hnf4a overexpression could largely rescue ypel5 deficiency-induced hepatic defects. Furthermore, PPARα signaling mediates the regulation of Hnf4a by Ypel5 through directly binding to the transcriptional enhancer of the Hnf4a gene. Herein, this work demonstrates an essential role of Ypel5 in hepatocyte proliferation and function and provides the first in vivo evidence for a physiological role of the ypel5 gene in vertebrates.

Animals

Renal conservation of antifreeze peptide in Antarctic eelpout, Rhigophila dearborni.

In Antarctic notothenioid fishes large amounts (3% w/v) of small molecular weights of 2,600-23,500 and would be expected to be filtered into the urine, they remain in the blood because the kidneys of these fishes contain only aglomerular nephrons. Unlike the situation in most fishes, urine formation is the result of secretion rather than filtration and reabsorption. On the other hand, the peptide antifreezes in Northern Hemisphere fishes such as the winter flounder. Pseudopleuronectes americanus, are retained by the glomerular kidney even though inulin, of comparable weight, is rapidly filtered from the blood into the urine. The Antarctic eelpout (zoarcid), Rhigophila dearborni, which is unrelated to either the Antarctic notothenioids or P. americanus, also uses a peptide antifreeze (molecular weight 6,000) which is maintained at a concentration of 3% (w/v) in the blood plasma. We report here that the lack of antifreeze in the urine of R. dearborni probably reflects the fact that the glomeruli are not functional and cannot filter. We support this conclusion with morphological and physiological evidence and relate our findings to the conservation of biological antifreeze necessary for life in ice-laden polar waters.

Adaptation, Biological

Identification of a putative novel polycyclic aromatic hydrocarbon-biodegrading gene cluster in a marine Roseobacteraceae bacterium Sagittula sp. MA-2.

UNLABELLED: The ability to biodegrade polycyclic aromatic hydrocarbons (PAHs) and the catabolic enzymes responsible for PAH biotransformation in marine bacteria belonging to the family Roseobacteraceae remain largely unexplored despite their wide distribution and highly diverse physiological traits. A bacterial isolate within Roseobacteraceae originating from coastal seawater, Sagittula sp. strain MA-2, that biotransformed phenanthrene and utilized it as a growth substrate was found to possess a putative PAH-degrading gene cluster on one of the eight circular plasmids in its genome. Subsequent comprehensive investigations utilizing bacterial genomes in public databases revealed that gene clusters potentially homologous to this newly found cluster are widely but heterogeneously distributed within Roseobacteraceae and a few non-Roseobacteraceae (Paracoccaceae and Rhizobiaceae) strains from saline environments. Catabolic functions of the enzymes encoded in strain MA-2 were predicted through the profiling of phenanthrene biotransformation products by liquid chromatography-electrospray ionization high-resolution mass spectrometry and substrate docking simulations using predicted three-dimensional structures of selected proteins, and phenanthrene biodegradation pathways were proposed. Strain MA-2 appeared to biodegrade phenanthrene via two separated, concurrent pathways, namely the salicylate and phthalate pathways. This study serves as the first investigation into the functional genes potentially responsible for PAH biodegradation conserved in Roseobacteraceae bacteria, expanding scientific understanding of the physiological repertoire evolved in this ubiquitous marine bacterial group. IMPORTANCE: The ocean is often characterized as the terminal destination for persistent polycyclic aromatic hydrocarbon (PAH) environmental pollutants; however, the ability to biodegrade PAHs and the corresponding enzymes conserved among marine bacteria are less understood compared to their terrestrial counterparts. A marine bacterial isolate, Sagittula sp. strain MA-2, belonging to the family Roseobacteraceae-a widely distributed and physiologically diverse marine bacterial group-was found to possess a functional gene cluster encoding enzymes potentially responsible for PAH biodegradation in its genome and exhibit the ability to biodegrade the three-ring PAH, phenanthrene. Intriguingly, gene clusters potentially homologous to this cluster were also distributed broadly across genomes from different Roseobacteraceae genera in public databases, which has not been previously investigated. The knowledge provided here expands our understanding of the physiology of Roseobacteraceae and may be applied to explore biotechnologically useful bacteria that contribute to the remediation of polluted marine environments or high-salinity wastewater.

Multigene Family