Biology subjects

Whitehead, A.

Publications and source records attributed to Whitehead, A..

14 recordsLinked to original sources

bioRxiv2026

Ocean acidification changes diet effects and differentially impacts two populations of red abalone (Haliotis rufescens)

Absorption of CO2 by global oceans is decreasing pH resulting in ocean acidification (OA). Impacts on shellfish have been documented in ecologically and commercially important species. We examined the influence of diet and OA between two populations of red abalone (Haliotis rufescens) a species of aquaculture importance and declining wild populations. Populations experience different exposure histories: strong upwelling (Van Damme, California [VD]) historically exposed to low-pH conditions and weak-intermittent upwelling (Santa Barbara, California [SB]). Abalone were cultured under control-pH or OA-conditions and fed crustose coralline algae (CCA) or diatoms used in aquaculture. We tested treatment effects of population, settlement diet, and OA-exposure on survival as influenced by larval-energy stores. Survival in both populations was enhanced by CCA when cultured under both treatment conditions; however, by later stages, this effect remained only for SB. SB had reduced post-settlement survival when cultured under OA-conditions, whereas post-settlement survival of VD was not. Diet affected the relationship between larval-energy and post-settlement survival; a positive relationship when fed diatoms and a negative relationship with CCA. The relationship between larval energy and post-settlement survival was stronger in VD. CCA enhanced juvenile growth in SB cultured abalone at both three-months and one-year post-settlement. Settlement diets can reduce the impacts of OA on early-life stages of abalone, but population differences driven by underlying energetics affect the consistency of this outcome. These findings illuminate the impacts from OA, suggesting populations may be at risk, and inform strategies for developing and sustaining shellfish aquaculture in the face of changing ocean conditions.

physiology↗

bioRxiv2026

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{degrees}C and 18{degrees}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.

evolutionary biology↗

bioRxiv2026

An innate immune circuit involving the lectin pathway, complement and lung epithelial cells enforce barrier immunity to inhaled fungal disease

The lung mucosal barrier thwarts many inhaled pathogens, including Coccidioides, the causative agent of Valley Fever. Because the earliest stages of pathogen recognition in the lung remain obscure, we investigated the initial events of barrier immunity in a murine model involving inhalation of Coccidioides sp. arthroconidia. Neutrophils accumulated rapidly, within 24 hours, near fungal spores in the bronchiolar airways. This response was driven by pattern recognition via the lectin complement pathway. Bronchiolar club cells propagated C3a signals and amplified the response via convergent C3aR and P2X7 signaling. We identified several MBL2 and P2RX7 polymorphisms that correlated with progressive disease in humans. Our assays revealed that these mutations caused functional impairments in C3a generation and P2X7 responsiveness. Our findings establish how complement signaling and epithelial sensing coordinate early immune responses to fungal infection, offering insights into essential host defense mechanisms and risk factors for disease progression in coccidioidomycosis.

microbiology↗

bioRxiv2025

Highly and lowly domesticated endangered fish from a conservation hatchery diverge in their thermal physiology, transcriptome, and methylome

Conservation hatcheries aim to produce fish for supplementation of wild populations, but hatchery environments may drive phenotypic divergence from wild fish. These diverged traits may have reduced fitness in the wild, which could compromise wild population sustainability and evolutionary potential, such as in response to climate change. Delta smelt are a critically endangered fish species that are safeguarded against extinction with a hatchery refuge population. We investigated whether elevated rearing temperature through larval development adjusted upper thermal tolerance limits (acclimation) in Delta smelt, whether upper thermal tolerance and plasticity (acclimation ability) differed between fish with old or recent hatchery ancestry (high or low domestication index; DI), and temperature and DI effects on liver transcriptome and methylome patterns. We observed that elevated rearing temperatures induced higher thermal tolerance (acclimation). Individuals with higher DI also had higher upper thermal tolerances, but high DI families had reduced thermal plasticity between rearing temperatures. This is consistent with domestication causing heritable elevation of upper thermal tolerance but at the cost of reduced thermal plasticity. High and low DI fish were differentiated in both genetic variation and methylome variation, suggesting the influence of both during domestication. But methylome differences distinguishing high and low DI fish did not overlap with temperature-induced methylome changes, and do not appear to be stably inherited in the hatchery. We conclude that domestication selection has altered thermal physiology within the refuge hatchery despite careful genetic management, underpinned by shifts in the transcriptome and methylome. These changes could affect Delta smelt fitness upon reintroduction to habitats that continue to warm, and show that physiological traits can diverge even within carefully genetically managed hatchery populations.

evolutionary biology↗

bioRxiv2025

Evidence of positive polygenic selection following a series of environmental and demographic disasters in Pacific herring

The causes and consequences of population collapse and recovery are difficult to discern and therefore predict because historical data are often sparse, and environmental drivers may interact in complex ways. Yet the influence of environmental change can imprint in contemporary and historic DNA sequences, thereby offering clues about drivers of population dynamics. The Prince William Sound (PWS) stock of Pacific herring famously collapsed in the early 1990s following the Exxon Valdez oil spill (EVOS), yet the causes of the collapse and reasons for a persistent lack of recovery are controversial. Three seasons after the spill, the PWS population declined precipitously, coincident with repeated disease outbreaks, and has remained small across the three decades since. We use population genetics as a forensic tool to gain insight into the causes and consequences of the collapse. We tracked genome-wide genetic variation across time, spanning the period immediately after the spill but preceding the collapse (1991) and across three subsequent decades to 2017. We compared genetic change through time between the PWS population and two reference Alaska populations. We detected high genetic differentiation between the Bering Sea and the Gulf of Alaska, and relatively small but significant genetic structure within the Gulf of Alaska. No loss of genome-wide genetic diversity was observed in the PWS population after the collapse. We did not detect any evidence for selective sweeps at individual loci. However, using sensitive temporal covariance methods, we detected significant signatures of positive polygenic adaptation in the PWS population but not in either of the reference populations. Gene functional enrichment analysis is consistent with selection acting on immune function and pathways that regulate crude oil developmental toxicity in the period following the spill and collapse. This suggests that environmental perturbations unique to the PWS region, including oil spills and disease outbreaks, affected the fitness of resident fish, and shifted their population genetic trajectory.

evolutionary biology↗

bioRxiv2025

PBDE flame retardant exposure causes neurobehavioral and transcriptional effects in first-generation but not second-generation offspring fish

Environmental pollutants can have lasting effects that extend beyond the exposure period, potentially impacting multiple generations. Despite the widespread presence of polybrominated diphenyl ether (PBDE) flame retardants in the environment including oceans globally, there is limited understanding of their potential for multigenerational toxicity. We investigated whether exposures to 2,2,4,4,5-pentaBDE (BDE-99), a predominant PBDE congener, can induce neurobehavioral and molecular effects across two generations using the marine vertebrate model fish Fundulus heteroclitus (Atlantic killifish). To assess how exposure route influences outcomes, we conducted two complementary experiments: in the progenitor exposure experiment, adult fish were exposed to BDE-99 through diet, leading to maternal transfer into F1 eggs, while in the direct embryonic exposure experiment, embryos were exposed to BDE-99 via waterborne exposure, achieving comparable embryonic doses. Both exposure routes resulted in altered photomotor responses in F1 larvae, but additional effects differed by exposure route. In the progenitor exposure, maternally exposed F1 juvenile fish exhibited reduced anxiety-like behavior and changes in brain gene expression, while in the direct embryonic exposure, F0 fish showed no detectable effects within their generation but caused behavioral alterations in F1 descendants. The lack of effects in direct F0 individuals suggests that neurobehavioral effects observed in maternally exposed F1 fish were not solely due to BDE-99 transfer but were influenced by additional maternal factors. In the progenitor exposure, neither behavioral nor gene expression effects persisted in the F2 generation. We conclude that maternal influences play a key role in shaping multigenerational effects of BDE-99 exposure, as indicated by the strong effects observed in maternally exposed F1 fish but not in F2 descendants, as well as the differences between maternally exposed fish and those exposed to comparable doses of BDE-99 alone.

pharmacology and toxicology↗

bioRxiv2025

Early-life PBDE flame retardant exposures cause neurobehavioral alterations in fish that persist into adulthood and vary by sex and route of exposure

Developing organisms exhibit varying susceptibility to environmental pollutants depending on the timing of exposure during development. Early-life development is particularly vulnerable, and many marine species spend early life in nearshore environments, elevating their risk of pollutant exposure. Polybrominated diphenyl ether (PBDE) flame retardants are persistent and ubiquitous pollutants, particularly in nearshore marine environments. They disrupt early-life development and pose ongoing risks for ocean health. However, whether early-life exposure influences neurotoxic effects, and whether those effects are durable throughout life, remains poorly understood. Using Fundulus heteroclitus, we tested whether early-life exposure to 2,2,4,4,5-pentaBDE (BDE-99) leads to persistent behavioral and molecular alterations in adulthood and whether outcomes differ by exposure route. We conducted two complementary experiments comparing progenitor (maternal) exposure and direct waterborne exposure during embryonic development. Similar doses to developing fish were achieved in both experiments. After hatch, all fish were reared in clean water until adulthood over two years later, at which time we assessed impacts on behavior and brain gene expression. Both exposure routes led to long-term hyperactivity and reduced anxiety-like behavior, but specific effects varied by dose and sex. Progenitor exposure altered behavior and the brain transcriptome in F1 males (females not tested), whereas direct embryonic exposure affected behavior in females and not males. These findings highlight the importance of maternal influences, such as chemical metabolites, altered lipid provisioning, small molecules, and epigenetic imprinting, alongside chemical transfer, in shaping the long-term persistence of behavioral and molecular effects from early-life exposure. The distinct effects between exposure routes suggest that dosing with chemical alone is not the only determinant of toxicity. We conclude that maternal factors that are modified by exposure significantly contribute to health outcomes in developing offspring, emphasizing the need to consider exposure route when assessing risks from persistent pollutants. Given that maternal and environmental exposures co-occur in nature, future studies should assess their combined impacts to better predict real-world risks.

pharmacology and toxicology↗

bioRxiv2025

Multiple stressors in the Anthropocene: Urban evolutionary history modifies sensitivity to the toxic effects of crude oil exposure in killifish

Persistence of wild species in human-altered environments is difficult, in part because challenges to fitness are complex when multiple environmental changes occur simultaneously, which is common in the Anthropocene. This complexity is difficult to conceptualize because the nature of environmental change is often highly context specific. A mechanism-guided approach may help to shape intuition and predictions about complexity; fitness challenges posed by co-occurring stressors with similar mechanisms of action may be less severe than for those with different mechanisms of action. We approach these considerations within the context of ecotoxicology because this field is built upon a rich mechanistic foundation. We hypothesized that evolved resistance to one class of common toxicants would afford resilience to the fitness impacts of another class of common toxicants that shares mechanisms of toxicity. Fundulus killifish populations in urban estuaries have repeatedly evolved resistance to persistent organic pollutants including PCBs. Since PCBs and some of the toxicants that constitute crude oil (e.g., high molecular weight PAHs) exert toxicity through perturbation of AHR signaling, we predicted that PCB resistant populations would also be resilient to crude oil toxicity. Common garden comparative oil exposure experiments, including killifish populations with different exposure histories, showed that most killifish populations were sensitive to fitness impacts (reproduction and development) caused by oil exposure, but that fish from the PCB-resistant population were insensitive. Population differences in toxic outcomes were not compatible with random-neutral expectations. Transcriptomics revealed that the molecular mechanisms that contributed to population variation in PAH resilience were shared with those that contribute to evolved variation in PCB resilience. We conclude that the fitness challenge posed by environmental pollutants is effectively reduced when those chemicals share mechanisms that affect fitness. Mechanistic considerations may help to scale predictions regarding the fitness challenges posed by stressors that may co-occur in human-altered environments.

evolutionary biology↗

bioRxiv2025

Adult killifish exposure to crude oil perturbs embryonic gene expression and larval morphology in first- and second-generation offspring

Exposures to environmental toxicants can have both immediate and long-term impacts, including those that persist into the next generation. Using Gulf killifish (Fundulus grandis), we tested whether adult progenitor exposure to crude oil caused perturbations to larval morphology and embryonic genome-wide gene expression in their first- and second-generation descendants raised in clean water. We also tracked responses of additional direct oil exposures in the F1 and F2 embryos. Exposure to oil in progenitor fish caused altered larval morphology in F1 and F2 descendants. Some perturbations were enhanced by additional oil exposure in lineages with progenitors that had been exposed to oil. Progenitor exposures altered embryonic gene expression in F1 and F2 descendants, implicating impacts on neurological and cardiovascular systems. Molecular responses to progenitor exposure were distinct between F1 and F2 offspring, suggesting complex interactions between mechanisms that contribute to the transgenerational transfer of information. In contrast, molecular responses to additional direct oil exposures during early-life development were highly conserved between generations and between progenitor exposure treatments. We conclude that exposure to crude oil causes developmental perturbations that propagate at least two generations, and we present additional hypotheses about underlying molecular mechanisms and emergent health consequences. SYNOPSISThis study shows that exposure of adult fish to crude oil perturbs development and gene expression in offspring and grand-offspring, thereby extending the timeframe necessary to consider ecotoxicological risk.

pharmacology and toxicology↗

bioRxiv2023

Independently evolved pollution resistance in four killifish populations is largely explained by few variants of large effect

The genetic architecture of phenotypic traits can affect the mode and tempo of trait evolution. Human-altered environments can impose strong natural selection, where successful evolutionary adaptation requires swift and large phenotypic shifts. In these scenarios, theory predicts the influence of few adaptive variants of large effect, but empirical studies that have revealed the genetic architecture of rapidly evolved phenotypes are rare, especially for populations inhabiting polluted environments. Fundulus killifish have repeatedly evolved adaptive resistance to extreme pollution in urban estuaries. Prior studies, including genome scans for signatures of natural selection, have revealed some of the genes and pathways important for evolved pollution resistance, and provide context for the genotype-phenotype association studies reported here. We created multiple quantitative trait locus (QTL) mapping families using progenitors from four different resistant populations, and genetically mapped variation in sensitivity (developmental perturbations) following embryonic exposure to a model toxicant PCB-126. We found that a few large-effect QTL loci accounted for resistance to PCB- mediated developmental toxicity. QTLs harbored candidate genes that govern the regulation of aryl hydrocarbon receptor (AHR) signaling, where some (but not all) of these QTL loci were shared across all populations, and some (but not all) of these loci showed signatures of recent natural selection in the corresponding wild population. Some strong candidate genes for PCB resistance inferred from genome scans in wild populations were identified as QTL, but some key candidate genes were not. We conclude that rapidly evolved resistance to the developmental defects normally caused by PCB-126 is governed by few genes of large effect. However, other aspects of resistance beyond developmental phenotypes may be governed by additional loci, such that comprehensive resistance to PCB-126, and to the mixtures of chemicals that distinguish urban estuaries more broadly, may be more genetically complex.

evolutionary biology↗

bioRxiv2022

Evidence of prezygotic isolation, but not assortative mating, between locally adapted populations of Fundulus heteroclitus across a salinity gradient

Selection along environmental gradients can drive reproductive isolation and speciation. Among fishes, salinity is a major factor limiting species distributions and, despite its importance in generating species diversity, transitions between marine and freshwater are rare. Here, we tested for mechanisms of reproductive isolation between locally adapted freshwater and brackish water-native populations of killifish, Fundulus heteroclitus, from either side of a hybrid zone along a salinity gradient. There was evidence for pre-zygotic endogenous reproductive isolation with reduced fertilization success between crosses of freshwater-native males and brackish water-native females. Exogenous pre-zygotic isolation was also present where females had highest fertilization in their native salinity. We used a replicated mass spawning design to test for mate choice in both brackish and fresh water. After genotyping 187 parents and 2,523 offspring at 2,347 SNPs across the genome, 85% of offspring were successfully assign to their parents. However, no reinforcing mate choice was observed. These results therefore demonstrate emerging, yet limited, reproductive isolation and incipient speciation across a marine to freshwater salinity gradient and suggest that both endogenous and exogenous mechanisms, but not assortative mating, contribute to divergence.

evolutionary biology↗

bioRxiv2019

Life out of water: Genomic and physiological mechanisms underlying skin phenotypic plasticity

The Devonian radiation of vertebrates from aquatic into terrestrial habitats required behavioral, physiological, and morphological adaptations. Changes to skin structure and function were likely crucial, but adaptations were needed to resolve contrasting demands of maintaining a mechanical and physiological barrier while also facilitating ion and gas transport. Little is known of the mechanisms that underlie skin plasticity and adaptation between water and air. We performed experiments using two isogenic lineages of an amphibious killifish (Kryptolebias marmoratus from brackish and freshwater habitats) and used transcriptional and morphological data to reveal mechanisms recruited to resolve the dual challenges of skin providing both a barrier and an exchange interface during terrestrial acclimation. Transcriptional regulators of skin morphogenesis were quickly activated upon emersion. Regulation of cell-cell adhesion complexes, coupled with pathways homologous with those that regulate stratum corneum formation, was consistent with barrier function and mechanical reinforcement. Cutaneous respiration was associated with regulation of angiogenesis pathways and with blood vessel architecture that facilitated extremely short diffusion distances and direct delivery to ionocyotes. Evolutionary analyses revealed directional selection operating on proteins involved in barrier and respiratory functions, reinforcing the importance of these mechanisms for enabling the amphibious lifestyle of K. marmoratus. Fish from brackish niches were more resilient to emersion and also differed from freshwater fish in ionoregulatory responses to emersion. We conclude that plasticity of barrier, respiratory, and ionoregulatory functions in skin evolved to support the amphibious lifestyle of K. marmoratus; similar processes may have facilitated the terrestrial radiation of ancient fishes.\n\nSignificance statementThe transition of vertebrate life from water to land coincided with solving multiple physiological challenges including avoiding drying out while also exchanging gases and ions with the environment. Though changes in the skin were likely important, little is known of the mechanisms that underlie skin flexibility and adaptation between water and air. We performed air exposure experiments with an amphibious killifish; gene expression profiling, microscopy, and evolutionary analysis of proteins revealed cell structures, proteins, and molecular pathways that support skin flexibility and adaptations during air exposure, and ion regulation contributed to differences in killifish abilities to adjust to air. Amphibious killifish are useful models to help us understand changes that enable water to air transitions in contemporary and ancient fishes.

physiology↗

bioRxiv2019

Draft genome assemblies using sequencing reads from Oxford Nanopore Technology and Illumina platforms for four species of North American killifish from the Fundulus genus

Draft de novo reference genome assemblies were obtained from four North American killifish species (Fundulus xenicus, Fundulus catenatus, Fundulus nottii, and Fundulus olivaceus) using sequence reads from Illumina and Oxford Nanopore Technologies PromethION platforms. For each species, the PromethION platform was used to generate 30-45x sequence coverage, and the Illumina platform was used to generate 50-160x sequence coverage. Contig N50 values ranged from 0.4 Mb to 2.7 Mb, and BUSCO scores were consistently above 90% complete using the Eukaryota database. Draft assemblies and raw sequencing data are available for public use. We encourage use and re-use of these data for assembly benchmarking and external analyses.

genomics↗

bioRxiv2018

Genome-wide selection scans integrated with association mapping reveal mechanisms of physiological adaptation across a salinity gradient in killifish

Adaptive divergence between marine and freshwater environments is important in generating phyletic diversity within fishes, but the genetic basis of adaptation to freshwater habitats remains poorly understood. Available approaches to detect adaptive loci include genome scans for selection, but these can be difficult to interpret because of incomplete knowledge of the connection between genotype and phenotype. In contrast, genome wide association studies (GWAS) are powerful tools for linking genotype to phenotype, but offer limited insight into the evolutionary forces shaping variation. Here, we combine GWAS and selection scans to identify loci important in the adaptation of complex physiological traits to freshwater environments. We focused on freshwater (FW)-native and brackish water (BW)-native populations of the Atlantic killifish (Fundulus heteroclitus) as well as a population that is a natural admixture of these two populations. We measured phenotypes for multiple physiological traits that differ between populations and that may contribute to adaptation across osmotic niches (salinity tolerance, hypoxia tolerance, metabolic rate, and body shape) and used a reduced representation approach for genome-wide genotyping. Our results show patterns of population divergence in physiological capabilities that are consistent with local adaptation. Selection scans between BW-native and FW-native populations identified genomic regions that presumably aect fitness between BW and FW environments, while GWAS revealed loci that contribute to variation for each physiological trait. There was substantial overlap in the genomic regions putatively under selection and loci associated with the measured physiological traits, suggesting that these phenotypes are important for adaptive divergence between BW and FW environments. Our analysis also implicates candidate genes likely involved in physiological capabilities, some of which validate a priori hypotheses. Together, these data provide insight into the mechanisms that enable diversification of fishes across osmotic boundaries.\n\nAuthor SummaryIdentifying the genes that underlie adaptation is important for understanding the evolutionary process, but this is technically challenging. We bring multiple lines of evidence to bear for identifying genes that underlie adaptive divergence. Specifically, we integrate genotype-phenotype association mapping with genome-wide scans for signatures of natural selection to reveal genes that underlie phenotypic variation and that are adaptive in populations of killifish that are diverging between marine and freshwater environments. Because adaptation is likely manifest in multiple physiological traits, we focus on hypoxia tolerance, salinity tolerance, and metabolic rate; traits that are divergent between marine and freshwater populations. We show that each of these phenotypes is evolving by natural selection between environments; genetic variants that contribute to variation in these physiological traits tend to be evolving by natural selection between marine and freshwater populations. Furthermore, one of our top candidate genes provides a mechanistic explanation for previous hypotheses that suggest the adaptive importance of cellular tight junctions. Together, these data demonstrate a powerful approach to identify genes involved in adaptation and help to reveal the mechanisms enabling transitions of fishes across osmotic boundaries.

evolutionary biology↗