Phenotypic plasticity can serve as a stepping stone towards adaptation. Recently, studies have shown that gene expression contributes to emergent stress responses such as thermal tolerance, with ...tolerant and susceptible populations showing distinct transcriptional profiles. However, given the dynamic nature of gene expression, interpreting transcriptomic results in a way that elucidates the functional connection between gene expression and the observed stress response is challenging. Here, we present a conceptual framework to guide interpretation of gene expression reaction norms in the context of stress tolerance. We consider the evolutionary and adaptive potential of gene expression reaction norms and discuss the influence of sampling timing, transcriptomic resilience, as well as complexities related to life history when interpreting gene expression dynamics and how these patterns relate to host tolerance. We highlight corals as a case study to demonstrate the value of this framework for non‐model systems. As species face rapidly changing environmental conditions, modulating gene expression can serve as a mechanistic link from genetic and cellular processes to the physiological responses that allow organisms to thrive under novel conditions. Interpreting how or whether a species can employ gene expression plasticity to ensure short‐term survival will be critical for understanding the global impacts of climate change across diverse taxa.
Psoriasis is a common inflammatory skin disease that has been reported to be associated with obesity. We aimed to investigate a possible causal relationship between body mass index (BMI) and ...psoriasis.
Following a review of published epidemiological evidence of the association between obesity and psoriasis, mendelian randomization (MR) was used to test for a causal relationship with BMI. We used a genetic instrument comprising 97 single-nucleotide polymorphisms (SNPs) associated with BMI as a proxy for BMI (expected to be much less confounded than measured BMI). One-sample MR was conducted using individual-level data (396,495 individuals) from the UK Biobank and the Nord-Trøndelag Health Study (HUNT), Norway. Two-sample MR was performed with summary-level data (356,926 individuals) from published BMI and psoriasis genome-wide association studies (GWASs). The one-sample and two-sample MR estimates were meta-analysed using a fixed-effect model. To test for a potential reverse causal effect, MR analysis with genetic instruments comprising variants from recent genome-wide analyses for psoriasis were used to test whether genetic risk for this skin disease has a causal effect on BMI. Published observational data showed an association of higher BMI with psoriasis. A mean difference in BMI of 1.26 kg/m2 (95% CI 1.02-1.51) between psoriasis cases and controls was observed in adults, while a 1.55 kg/m2 mean difference (95% CI 1.13-1.98) was observed in children. The observational association was confirmed in UK Biobank and HUNT data sets. Overall, a 1 kg/m2 increase in BMI was associated with 4% higher odds of psoriasis (meta-analysis odds ratio OR = 1.04; 95% CI 1.03-1.04; P = 1.73 × 10(-60)). MR analyses provided evidence that higher BMI causally increases the odds of psoriasis (by 9% per 1 unit increase in BMI; OR = 1.09 (1.06-1.12) per 1 kg/m2; P = 4.67 × 10(-9)). In contrast, MR estimates gave little support to a possible causal effect of psoriasis genetic risk on BMI (0.004 kg/m2 change in BMI per doubling odds of psoriasis (-0.003 to 0.011). Limitations of our study include possible misreporting of psoriasis by patients, as well as potential misdiagnosis by clinicians. In addition, there is also limited ethnic variation in the cohorts studied.
Our study, using genetic variants as instrumental variables for BMI, provides evidence that higher BMI leads to a higher risk of psoriasis. This supports the prioritization of therapies and lifestyle interventions aimed at controlling weight for the prevention or treatment of this common skin disease. Mechanistic studies are required to improve understanding of this relationship.
Epigenetic mechanisms underlying phenotypic change are hypothesized to contribute to population persistence and adaptation in the face of environmental change. To date, few studies have explored the ...heritability of intergenerationally stable methylation levels in natural populations, and little is known about the relative contribution of cis- and trans-regulatory changes to methylation variation. Here, we explore the heritability of DNA methylation, and conduct methylation quantitative trait loci (meQTLs) analysis to investigate the genetic architecture underlying methylation variation between marine and freshwater ecotypes of threespine stickleback (Gasterosteus aculeatus). We quantitatively measured genome-wide DNA methylation in fin tissue using reduced representation bisulfite sequencing of F1 and F2 crosses, and their marine and freshwater source populations. We identified cytosines (CpG sites) that exhibited stable methylation levels across generations. We found that additive genetic variance explained an average of 24-35% of the methylation variance, with a number of CpG sites possibly autonomous from genetic control. We also detected both cis- and trans-meQTLs, with only trans-meQTLs overlapping with previously identified genomic regions of high differentiation between marine and freshwater ecotypes. Finally, we identified the genetic architecture underlying two key CpG sites that were differentially methylated between ecotypes. These findings demonstrate a potential role for DNA methylation in facilitating adaptation to divergent environments and improve our understanding of the heritable basis of population epigenomic variation.
Environmental DNA (eDNA) methods are used to detect DNA that is shed into the aquatic environment by cryptic or low density species. Applied in eDNA studies, occupancy models can be used to estimate ...occurrence and detection probabilities and thereby account for imperfect detection. However, occupancy terminology has been applied inconsistently in eDNA studies, and many have calculated occurrence probabilities while not considering the effects of imperfect detection. Low detection of invasive giant constrictors using visual surveys and traps has hampered the estimation of occupancy and detection estimates needed for population management in southern Florida, USA. Giant constrictor snakes pose a threat to native species and the ecological restoration of the Florida Everglades. To assist with detection, we developed species-specific eDNA assays using quantitative PCR (qPCR) for the Burmese python (Python molurus bivittatus), Northern African python (P. sebae), boa constrictor (Boa constrictor), and the green (Eunectes murinus) and yellow anaconda (E. notaeus). Burmese pythons, Northern African pythons, and boa constrictors are established and reproducing, while the green and yellow anaconda have the potential to become established. We validated the python and boa constrictor assays using laboratory trials and tested all species in 21 field locations distributed in eight southern Florida regions. Burmese python eDNA was detected in 37 of 63 field sampling events; however, the other species were not detected. Although eDNA was heterogeneously distributed in the environment, occupancy models were able to provide the first estimates of detection probabilities, which were greater than 91%. Burmese python eDNA was detected along the leading northern edge of the known population boundary. The development of informative detection tools and eDNA occupancy models can improve conservation efforts in southern Florida and support more extensive studies of invasive constrictors. Generic sampling design and terminology are proposed to standardize and clarify interpretations of eDNA-based occupancy models.
Background Sensory nerves innervating the airways play an important role in regulating various cardiopulmonary functions, maintaining homeostasis under healthy conditions and contributing to ...pathophysiology in disease states. Hypo-osmotic solutions elicit sensory reflexes, including cough, and are a potent stimulus for airway narrowing in asthmatic patients, but the mechanisms involved are not known. Transient receptor potential cation channel, subfamily V, member 4 (TRPV4) is widely expressed in the respiratory tract, but its role as a peripheral nociceptor has not been explored. Objective We hypothesized that TRPV4 is expressed on airway afferents and is a key osmosensor initiating reflex events in the lung. Methods We used guinea pig primary cells, tissue bioassay, in vivo electrophysiology, and a guinea pig conscious cough model to investigate a role for TRPV4 in mediating sensory nerve activation in vagal afferents and the possible downstream signaling mechanisms. Human vagus nerve was used to confirm key observations in animal tissues. Results Here we show TRPV4-induced activation of guinea pig airway–specific primary nodose ganglion cells. TRPV4 ligands and hypo-osmotic solutions caused depolarization of murine, guinea pig, and human vagus and firing of Aδ-fibers (not C-fibers), which was inhibited by TRPV4 and P2X3 receptor antagonists. Both antagonists blocked TRPV4-induced cough. Conclusion This study identifies the TRPV4-ATP-P2X3 interaction as a key osmosensing pathway involved in airway sensory nerve reflexes. The absence of TRPV4-ATP–mediated effects on C-fibers indicates a distinct neurobiology for this ion channel and implicates TRPV4 as a novel therapeutic target for neuronal hyperresponsiveness in the airways and symptoms, such as cough.
Adaptation to environmental conditions, and the mechanisms underlying these adaptations, can vary greatly among species. This variation can be attributed to a variety of factors including the ...strength of evolutionary processes like selection, gene flow, time since divergence, and/or genetic drift, as well as the interactions between these processes. A number of simulation and theoretical studies have helped elucidate the role of these processes on the genomic basis of adaptation (Schaal et al., 2022; Yeaman et al., 2016). However, complementary empirical studies to test these theoretical expectations for within‐species adaptation have been limited due to the challenging nature of evaluating these processes in a comparative framework. To do this effectively, it is necessary to have systems where the range of environmental variation is similar between species, but where one or more of these evolutionary processes vary. In a From the Cover article in this issue of Molecular Ecology, Shi et al. (2022) provide an excellent example of a freshwater system where rates of gene flow differ between populations of six riverine species due to variation in spawning strategies (i.e., broadcast spawners = high gene flow, nest spawners = low gene flow), but all experience the same variation in environmental conditions across their distributions. The authors take a multivariate approach to evaluate the genomic basis of adaptation by using a combination of differentiation‐based and genotype‐environment association (GEA) methods. By comparing the amount of gene flow between species and the resulting genomic basis of local adaptation, they are able to infer how genomic architecture may be shaped by rates of gene flow. Their results identify a general pattern of increased genomic clustering in species with increasing levels of gene flow. However, two of six species did not follow this pattern, which could be due to additional factors not assessed. Additionally, they provide convincing evidence that the underlying evolutionary mechanisms that formed genomic clusters within each species vary. These deviations from a general pattern highlight how difficult evaluating these processes in natural populations are, particularly because species‐specific responses can vary dramatically. Taken together, their comparative framework for assessing the genomic architecture of adaptation is unique, sheds important light on how evolutionary processes can impact adaptation, and provides robust empirical support of foundational theoretical and simulation studies.
Objective: A previously published randomized clinical trial indicated that a developmental behavioral intervention, the Early Start Denver Model (ESDM), resulted in gains in IQ, language, and ...adaptive behavior of children with autism spectrum disorder. This report describes a secondary outcome measurement from this trial, EEG activity. Method: Forty-eight 18- to 30-month-old children with autism spectrum disorder were randomized to receive the ESDM or referral to community intervention for 2 years. After the intervention (age 48 to 77 months), EEG activity (event-related potentials and spectral power) was measured during the presentation of faces versus objects. Age-matched typical children were also assessed. Results: The ESDM group exhibited greater improvements in autism symptoms, IQ, language, and adaptive and social behaviors than the community intervention group. The ESDM group and typical children showed a shorter Nc latency and increased cortical activation (decreased alpha power and increased theta power) when viewing faces, whereas the community intervention group showed the opposite pattern (shorter latency event-related potential ERP and greater cortical activation when viewing objects). Greater cortical activation while viewing faces was associated with improved social behavior. Conclusions: This was the first trial to demonstrate that early behavioral intervention is associated with normalized patterns of brain activity, which is associated with improvements in social behavior, in young children with autism spectrum disorder. (Contains 5 figures.)
Identification of microsatellites, or simple sequence repeats (SSRs), can be a time-consuming and costly investment requiring enrichment, cloning, and sequencing of candidate loci. Recently, however, ...high throughput sequencing (with or without prior enrichment for specific SSR loci) has been utilized to identify SSR loci. The direct "Seq-to-SSR" approach has an advantage over enrichment-based strategies in that it does not require a priori selection of particular motifs, or prior knowledge of genomic SSR content. It has been more expensive per SSR locus recovered, however, particularly for genomes with few SSR loci, such as bird genomes. The longer but relatively more expensive 454 reads have been preferred over less expensive Illumina reads. Here, we use Illumina paired-end sequence data to identify potentially amplifiable SSR loci (PALs) from a snake (the Burmese python, Python molurus bivittatus), and directly compare these results to those from 454 data. We also compare the python results to results from Illumina sequencing of two bird genomes (Gunnison Sage-grouse, Centrocercus minimus, and Clark's Nutcracker, Nucifraga columbiana), which have considerably fewer SSRs than the python. We show that direct Illumina Seq-to-SSR can identify and characterize thousands of potentially amplifiable SSR loci for as little as $10 per sample--a fraction of the cost of 454 sequencing. Given that Illumina Seq-to-SSR is effective, inexpensive, and reliable even for species such as birds that have few SSR loci, it seems that there are now few situations for which prior hybridization is justifiable.
Significance In the surface ocean, organic matter released by phytoplankton and degraded by heterotrophic bacteria is a key step in the carbon cycle. Compounds important in this trophic link are ...poorly known, in part because of the thousands of chemicals making up marine dissolved organic matter. We cocultured a Roseobacter clade bacterium with the diatom Thalassiosira pseudonana and used gene expression changes to assay for compounds passed to the bacterium. A C ₃-sulfonate with no previously known role in the microbial food web was identified and subsequently shown to be an abundant diatom metabolite and actively cycling compound in seawater. This work identifies a missing component of the marine carbon and sulfur cycles.
About half the carbon fixed by phytoplankton in the ocean is taken up and metabolized by marine bacteria, a transfer that is mediated through the seawater dissolved organic carbon (DOC) pool. The chemical complexity of marine DOC, along with a poor understanding of which compounds form the basis of trophic interactions between bacteria and phytoplankton, have impeded efforts to identify key currencies of this carbon cycle link. Here, we used transcriptional patterns in a bacterial-diatom model system based on vitamin B ₁₂ auxotrophy as a sensitive assay for metabolite exchange between marine plankton. The most highly up-regulated genes (up to 374-fold) by a marine Roseobacter clade bacterium when cocultured with the diatom Thalassiosira pseudonana were those encoding the transport and catabolism of 2,3-dihydroxypropane-1-sulfonate (DHPS). This compound has no currently recognized role in the marine microbial food web. As the genes for DHPS catabolism have limited distribution among bacterial taxa, T. pseudonana may use this sulfonate for targeted feeding of beneficial associates. Indeed, DHPS was both a major component of the T. pseudonana cytosol and an abundant microbial metabolite in a diatom bloom in the eastern North Pacific Ocean. Moreover, transcript analysis of the North Pacific samples provided evidence of DHPS catabolism by Roseobacter populations. Other such biogeochemically important metabolites may be common in the ocean but difficult to discriminate against the complex chemical background of seawater. Bacterial transformation of this diatom-derived sulfonate represents a previously unidentified and likely sizeable link in both the marine carbon and sulfur cycles.
Oceanic heatwaves have significant impacts on disease dynamics in marine ecosystems. Following an extreme heatwave in Nanoose Bay, British Columbia, Canada, a severe sea cucumber wasting event ...occurred that resulted in the mass mortality of
Here, we sought to determine if heat stress in isolation could trigger wasting symptoms in
. We exposed sea cucumbers to (i) a simulated marine heatwave (22 °C), (ii) an elevated temperature treatment (17 °C), or (iii) control conditions (12 °C). We measured the presence of skin lesions, mortality, posture maintenance, antipredator defences, spawning, and organ evisceration during the 79-hour thermal exposure, as well as 7-days post-exposure. Both the 22 °C and 17 °C treatments elicited stress responses where individuals exhibited a reduced ability to maintain posture and an increase in stress spawning. The 22 °C heatwave was particularly stressful, as it was the only treatment where mortality was observed. However, none of the treatments induced wasting symptoms as observed in the Nanoose Bay event. This study provides evidence that sea cucumber wasting may not be triggered by heat stress in isolation, leaving the cause of the mass mortality event observed in Nanoose unknown.
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