Biology subjects

Bolnick, D. I.

Publications and source records attributed to Bolnick, D. I..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Macroevolutionary changes in gene expression response to an immune stimulus across the diversity of fishes

Our understanding of the vertebrate immune system is dominated by a few model organisms such as mice. This use of a few model systems is reasonable if major features of the immune systems evolve slowly and are conserved across most vertebrates, but may be problematic if there is substantial macroevolutionary change in immune responses. Here, we present a test of the macroevolutionary stability, across 15 species of jawed fishes, of the transcriptomic response to a standardized immune challenge. Intraperitoneal injection of an immune adjuvant (alum) induces a fibrosis response in nearly all jawed fishes, which in some species contributes to anti-helminth resistance. Despite this conserved phenotypic response, the underlying transcriptomic response is highly inconsistent across species. Although many gene orthogroups exhibit differential expression between saline versus alum-injected fish in at least one species, few orthogroups exhibit consistent differential expression across species. This result suggests that although the phenotypic response to alum (fibrosis) is highly conserved, the underlying gene regulatory architecture is very flexible and cannot readily be extrapolated from any one species to fishes (or vertebrates) more broadly. The vertebrate immune response is remarkably changeable over macroevolutionary time, requiring a diversity of model organisms to describe effectively.

evolutionary biology↗

bioRxiv2024

Constitutive differences in immune gene expression and energy storage phenotypes co-vary with winter environment in wood frogs

Many terrestrial ectotherms have gone to great evolutionary lengths to adapt to long cold winters; some have even evolved the ability to tolerate the freezing of most of the water in the body. Now, however, high-elevation, and high-latitude winters are experiencing an accelerated period of warming. Specialized winter adaptations that promoted fitness in a seasonally frozen environment may soon be superfluous or even maladaptive. We ask whether winter adaptations include changes in immune functions, and whether changing winter conditions could exert disparate effects on populations of a wide-ranging terrestrial ectotherm, the wood frog (Lithobates sylvaticus). By rearing wood frogs from ancestral winter environments that vary in length and temperature in a common garden, and reciprocally exposing post-metamorphic frogs to unfrozen and frozen artificial winter conditions in the lab, we were able to decompose transcriptomic differences in ventral skin gene expression into those that were environmentally induced (responsive to temperature), genetically determined, and those that varied as an interaction between genotype and environment. We found that frogs from harsh ancestral winter environments constitutively upregulated immune processes, including cellular immunity, inflammatory processes, and adaptive immune processes, as compared to frogs from mild ancestral winter environments. Further, we saw that expression of several genes varied in an interaction between genotype and artificial winter. We suggest that just as winter climates likely served as the selective force resulting in remarkable winter adaptations such as freeze tolerance, they also induced constitutive changes in immune gene expression.

evolutionary biology↗

bioRxiv2024

Rates of evolution differ between cell types identified by single-cell RNAseq in threespine stickleback

Rates of evolutionary change vary by gene. While some broad gene categories are highly conserved with little divergence over time, others undergo continuous selection pressure and are highly divergent. Here, we combine single-cell RNA sequencing (scRNAseq) with evolutionary genomics to understand whether certain cell types exhibit faster evolutionary divergence (using their characteristic genes), than other types of cells. Merging scRNAseq with population genomic data, we show that cell types differ in the rate at which their characteristic genes evolve, as measured by allele frequency divergence among many populations (FST) and between species (dN/dS ratios). Neutrophils, B cells, and fibroblasts exhibit elevated FST at characteristic genes, while eosinophils in the intestine and thrombocytes in the head kidney exhibit lower FST than the average for 1000 random genes. Gene network centrality also differed between immune- and non-immune-associated genes, and closeness centrality was positively related to gene FST. These results highlight the value of merging single cell RNA sequencing technology with evolutionary population genomic data, and reveal that genes which define immune cell types exhibit especially rapid evolution.

evolutionary biology↗

bioRxiv2024

Effects of hybridization and gene flow on gene co-expression networks

Gene co-expression networks are a widely used tool for summarizing transcriptomic variation between individuals, and for inferring the transcriptional regulatory pathways that mediate genotype-phenotype relationships. However, these co-expression networks must be interpreted with caution, as they can arise from multiple processes. Here, we show that hybridization and gene flow between populations can greatly modify co-expression networks. Admixture between populations produces correlated expression between genes experiencing linkage disequilibrium. This correlated expression does not reflect functional relationships between genes, but rather depends on migration rates and physical linkage on chromosomes. Given the prevalence of gene flow between divergent populations in nature, these introgression effects likely represent a significant force in network evolution, even in populations where hybridization is historical rather than contemporary. These findings emphasize the critical importance of considering both evolutionary history and genomic architecture when analyzing gene co-expression networks in natural populations.

genetics↗

bioRxiv2024

Destabilized host-parasite dynamics in newly founded populations

When species disperse into previously unoccupied habitats, new populations encounter unfamiliar species interactions such as altered parasite loads. Theory predicts that newly founded populations should exhibit destabilized eco-evolutionary fluctuations in infection rates and immune traits. However, to understand founder effects biologists typically rely on retrospective studies of range expansions, missing early-generation infection dynamics. To remedy this, we experimentally founded whole-lake populations of threespine stickleback. Infection rates were temporally stable in native source lakes. In contrast, newly founded populations exhibit destabilized host-parasite dynamics: high starting infection rates led to increases in a heritable immune trait (peritoneal fibrosis), suppressing infection rates. The resulting temporal auto-correlation between infection and immunity suggest that newly founded populations can exhibit rapid host-parasite eco-evolutionary dynamics.

evolutionary biology↗

bioRxiv2024

A spectral framework to map QTLs affecting joint differential networks of gene co-expression

Studying the mechanisms underlying the genotype-phenotype association is crucial in genetics. Gene expression studies have deepened our understanding of the genotype [->] expression [->] phenotype mechanisms. However, traditional expression quantitative trait loci (eQTL) methods often overlook the critical role of gene co-expression networks in translating genotype into phenotype. This gap highlights the need for more powerful statistical methods to analyze genotype [->] network [->] phenotype mechanism. Here, we develop a network-based method, called snQTL, to map quantitative trait loci affecting gene co-expression networks. Our approach tests the association between genotypes and joint differential networks of gene co-expression via a tensor-based spectral statistics, thereby overcoming the ubiquitous multiple testing challenges in existing methods. We demonstrate the effectiveness of snQTL in the analysis of three-spined stickleback (Gasterosteus aculeatus) data. Compared to conventional methods, our method snQTL uncovers chromosomal regions affecting gene co-expression networks, including one strong candidate gene that would have been missed by traditional eQTL analyses. Our framework suggests the limitation of current approaches and offers a powerful network-based tool for functional loci discoveries. Significance statementThis work addresses a key gap in understanding the mechanistic foundations for genotype-phenotype associations. While existing expression quantitative trait loci (eQTL) methods identify candidate loci affecting gene expression variants, they often neglect the crucial role of gene co-expression networks. Here, we develop a network-based QTL framework to map genetic loci affecting the gene co-expression network. Utilizing a tensor-based spectral approach, our snQTL method estimates the differential co-expression patterns and effectively identifies the associated genetic loci. Application of snQTL to three-spined sticklebacks revealed candidate loci missed by standard methods. This work suggests the limitations of current approaches and highlights the potential of network-based functional loci discovery.

genetics↗

bioRxiv2023

Predictable and divergent change in the multivariate P-matrix during parallel adaptation

AbstractAdaptation to replicated environmental conditions can be remarkably predictable, suggesting parallel evolution may be a common feature of adaptive radiation. An open question, however, is how phenotypic variation itself evolves during repeated adaptation. Here, we use a dataset of morphological measurements from 35 populations of threespine stickleback, consisting of 16 parapatric lake- stream pairs and three marine populations, to understand how phenotypic variation has evolved during transitions from marine to freshwater environments, and during subsequent diversification across the lake-stream boundary. We find statistical support for divergent phenotypic covariance (P) across populations, with most diversification of P occurring across freshwater populations. Despite a close correspondence between within-population phenotypic variation and among population divergence, we find that variation in P is unrelated to total variation in population means across the set of populations. Within lake-stream pairs, however, we find that theoretical predictions for microevolutionary change can explain over 30% of the total divergence in P matrices across the habitat boundary. Together, our results indicate that variance evolution occurs primarily in dimensions of trait space with low phenotypic integration, driven by divergence into disparate lake and stream environments, illustrating how conserved and divergent features of multivariate variation can underlie adaptive radiation.

evolutionary biology↗

bioRxiv2023

Locomotor effects of a fibrosis-based immune response in stickleback fish

The vertebrate immune system provides an impressively effective defense against parasites and pathogens. However, these benefits must be balanced against a range of costly side-effects including energy loss and risks of auto-immunity. These costs might include biomechanical impairment of movement, but little is known about the intersection between immunity and biomechanics. Here, we show that a fibrosis immune response in threespine stickleback (Gasterosteus aculeatus) has collateral effects on their locomotion. When freshwater stickleback are infected with the tapeworm parasite Schistocephalus solidus, they face an array of fitness consequences ranging from impaired body condition and fertility to an increased risk of mortality. To fight the infection, some stickleback will initiate a fibrosis immune response in which they produce excess collagenous tissue in their coelom. Although fibrosis is effective at reducing infection, some populations of stickleback actively suppress this immune response, possibly because the costs of fibrosis outweigh the benefits. Here we quantify the locomotor effects of the fibrosis immune response in the absence of parasites to investigate whether there are collateral costs of fibrosis that could help explain why some fish forego this effective defense. To do this, we induce fibrosis in stickleback and then test their C-start escape performance. Additionally, we measure the severity of fibrosis, body stiffness, and body curvature during the escape response. We were able to estimate performance costs of fibrosis by including these variables as intermediates in a structural equation model. This model reveals that among control fish without fibrosis, there is a performance cost associated with increased body stiffness. However, fish with fibrosis did not experience this cost but rather displayed increased performance with higher fibrosis severity. This result demonstrates that the adaptive landscape of immune responses can be complex with the potential for wide reaching and unexpected fitness consequences.

evolutionary biology↗

bioRxiv2023

Opening a can of worms: a test of the coinfection facilitation hypothesis

Parasitic infections are a global occurrence and impact the health of many species. Coinfections, where two or more species of parasite are present in a host, are a common phenomenon across species. Coinfecting parasites can interact directly, or indirectly via their manipulation of (and susceptibility to) the immune system of their shared host. Helminths, such as the cestode Schistocephalus solidus, are well known to suppress immunity of their host (threespine stickleback, Gasterosteus aculeatus), potentially facilitating other parasite species. Yet, hosts can evolve a more robust immune response (as seen in some stickleback populations), potentially turning facilitation into inhibition. Using wild-caught stickleback from 21 populations with non-zero S. solidus prevalence, we tested an a priori hypothesis that S. solidus infection facilitates infection by other parasites. Consistent with this hypothesis, individuals with S. solidus infections have 18.6% higher richness of other parasites, compared to S. solidus-uninfected individuals from the same lakes. This facilitation-like trend is stronger in lakes where S. solidus is particularly successful but is reversed in lakes with sparse and smaller cestodes (indicative of stronger host immunity). These results suggest that a geographic mosaic of host-parasite coevolution might lead to a mosaic of between-parasite facilitation/inhibition effects.

ecology↗

bioRxiv2023

The dominance of coinfecting parasites' indirect effects on host traits

Indirect genetic effects (IGEs) exist when there is heritable variation in one species ability to alter a second species traits. For example, parasites can evolve disparate strategies to manipulate host immune response, whether by evading detection or suppressing immunity. A complication arises during coinfection, when two or more parasite genotypes may try to impose distinct IGEs on the same host trait: which parasites IGE will be dominant? Here, we apply the notion of dominance to IGEs during coinfection. Using a mathematical model we show that the dominance of IGEs can alter the evolutionary dynamics of parasites. We consider a resident parasite population receiving rare immigrants with a different immune manipulation trait. These immigrants relative fitness depends on resident prevalence (e.g., the probability immigrants are alone in a host, or coinfecting with a native), and the dominance of the immigrants IGE on host immunity. Next, we show experimentally that the cestode Schistocephalus solidus exerts an IGE on a host immune trait: parasite antigens from different populations produced different intensities of fibrosis. We then evaluated IGE dominance, finding evidence for overdominance (coinjected antigens induced an even stronger host immune response) which would be detrimental to immigrants when resident prevalence is high. This combination of experimental and modeling results shows that parasites do exhibit IGEs on host traits, and that the dominance of these IGEs during coinfection can substantially alter parasite evolution.

evolutionary biology↗

bioRxiv2022

Population genomics of a threespine stickleback tapeworm in Vancouver Island

We surveyed the genetic structuring of 12 Schistocephalus solidus tapeworm populations from Vancouver Island (BC, Canada) using ddRAD sequencing and compared it to that of their threespine stickleback fish hosts. There were small but mostly significant genetic differences among the tapeworm populations. PCA results separated the populations by watershed (from the lakes where the tapeworms were collected), but we could not determine if the genetic structures seen were due to discrete models (i.e. watershed) or to a continuous model (i.e. isolation by distance). However, the tapeworm genetic differences were significantly smaller (P < 0.001) than those of the fish, which indicates that the parasite disperses more readily than their fish hosts.

evolutionary biology↗

bioRxiv2022

Local adaptation and host specificity to copepod intermediate hosts by the Schistocephalus solidus tapeworm

We investigated if there was local adaptation and host specify in the tapeworm Schistocephalus solidus to its copepod first intermediate hosts. The tapeworm is locally adapted and host specific to its threespine stickleback second intermediate host. We exposed copepods from five lakes in Vancouver Island (BC, Canada) to local (i.e. same lake) and foreign tapeworms in a reciprocal exposure experiment. Results indicate that the tapeworm is not locally adapted to the copepods, but there was host specificity as a copepod genus was more parasitized than another genus.

evolutionary biology↗

bioRxiv2022

Evidence of divergent selection in a parasite due to its host immunological respond

We investigated if an immunological response (i.e. fibrosis) in threespine stickleback fish can cause divergent selection in its tapeworm Schistocephalus solidus. We pooled tapeworms from six populations in Vancouver Island (BC, Canada) and sequenced the whole genome of these pools. Then we used a modified Population Branch Statistics (PBS) technique based on FST comparisons to find loci under divergent selection due to fibrosis. We found at least eight loci under divergent selection in tapeworm populations caused by this strong immunological respond to infection from the fish.

evolutionary biology↗

bioRxiv2022

Elemental content of a host-parasite relationship in the threespine stickleback

Parasite infections are ubiquitous and their effects on hosts may play a role in ecosystem processes. Ecological stoichiometry provides a framework to study linkages between consumers and ecosystem process, but the stoichiometric traits of host-parasite associations are rarely quantified. Specifically, whether parasites elemental ratios closely resemble those of their host or if infection is related to host stoichiometry remains less known. To answer such questions, we measured the elemental content (%C, %N, and %P) and ratios (C:N, C:P, and N:P) of parasitized and unparasitized Gasterosteus aculeatus (three-spined stickleback) and their cestode parasite, Schistocephalus solidus. Host and parasite elemental content were distinct from each other, and parasites were generally higher in %C and lower in %N and %P. Parasite infections were related to some elemental ratios, specifically C:N, with more intense parasite infections corresponding to hosts with lower C:N ratio. Parasite stoichiometry was independent of their host and there was no relationship between host and parasite stoichiometry. Instead, parasite body mass and parasite density were important drivers of parasite stoichiometry where larger parasites had lower %C, %N, and %P. Overall, these potential effects of parasite infections on host stoichiometry along with parasites distinct elemental compositions suggest parasites may further contribute to how hosts store and cycle nutrients.

ecology↗

bioRxiv2021

Single-cell RNA sequencing reveals micro-evolution of the stickleback immune system

Pathogenic infection is an important driver of many ecological processes. Furthermore, variability in immune function is an important driver of differential infection outcomes. New evidence would suggest that immune variation extends to broad cellular structure of immune systems. However, variability at such broad levels is traditionally difficult to detect in non-model systems. Here we leverage single cell transcriptomic approaches to document signatures of microevolution of immune system structure in a natural system, the three-spined stickleback (Gasterosteus aculeatus). We sampled nine adult fish from three populations with variability in resistance to a cestode parasite, Schistocephalus solidus, to create the first comprehensive immune cell atlas for G. aculeatus. Eight major immune cell types, corresponding to major vertebrate immune cells, were identified. We were also able to document significant variation in both abundance and expression profiles of the individual immune cell types, among the three populations of fish. This variability may contribute to observed variability in parasite susceptibility. Finally, we demonstrate that identified cell type markers can be used to reinterpret traditional transcriptomic data. Combined our study demonstrates the power of single cell sequencing to not only document evolutionary phenomena (i.e. microevolution of immune cells), but also increase the power of traditional transcriptomic datasets.

immunology↗

bioRxiv2021

Evolution of a costly immunity to cestode parasites is a pyrrhic victory

Parasites impose fitness costs on their hosts. Biologists therefore tend to assume that natural selection favors infection-resistant hosts. Yet, when the immune response itself is costly, theory suggests selection may instead favor loss of resistance. Immune costs are rarely documented in nature, and there are few examples of adaptive loss of resistance. Here, we show that when marine threespine stickleback colonized freshwater lakes they gained resistance to the freshwater-associated tapeworm, Schistocephalus solidus. Extensive peritoneal fibrosis and inflammation contribute to suppression of cestode growth and viability, but also impose a substantial cost of reduced fecundity. Combining genetic mapping and population genomics, we find that the immune differences between tolerant and resistant populations arise from opposing selection in both populations acting, respectively, to reduce and increase resistance consistent with divergent optimization. One Sentence SummaryRecently-evolved freshwater populations of stickleback frequently evolve increased resistance to tapeworms, involving extensive fibrosis that suppresses parasite growth; because this fibrosis greatly reduces fish fecundity, in some freshwater populations selection has favored an infection-tolerant strategy with fibrosis suppression.

evolutionary biology↗

bioRxiv2021

Interacting Phenotypes and the Coevolutionary Process

Coevolution occurs when species interact to influence one anothers fitness, resulting in reciprocal evolutionary change. In many coevolving lineages, trait expression in one species is modified by the genotypes and phenotypes of the other, forming feedback loops reminiscent of models of intraspecific social evolution. Here, we adapt the theory of within-species social evolution, characterized by indirect genetic effects and social selection imposed by interacting individuals, to the case of interspecific interactions. In a trait-based model, we derive general expressions for multivariate evolutionary change in two species and the expected between-species covariance in evolutionary change when selection varies across space. We show that reciprocal interspecific indirect genetic effects can dominate the coevolutionary process and drive patterns of correlated evolution beyond what is expected from direct selection alone. In extreme cases, interspecific indirect genetic effects can lead to coevolution when selection does not covary between species or even when one species lacks genetic variance. Moreover, our model indicates that interspecific indirect genetic effects may interact in complex ways with cross-species selection to determine the course of coevolution. Importantly, our model makes empirically testable predictions for how different forms of reciprocal interactions contribute to the coevolutionary process.

evolutionary biology↗

bioRxiv2020

What evolutionary processes maintain MHCIIβ diversity within and among populations of stickleback?

Major Histocompatibility Complex (MHC) genes encode for proteins that recognize foreign protein antigens to initiate T-cell mediated adaptive immune responses. They are often the most polymorphic genes in vertebrate genomes. How evolution maintains this diversity is still an unsettled issue. Three main hypotheses seek to explain the maintenance of MHC diversity by invoking pathogen-mediated selection: heterozygote advantage, frequency-dependent selection, and fluctuating selection across landscapes or through time. Here, we use a large-scale field parasite survey in a stickleback metapopulation to test predictions derived from each of these hypotheses. We identify over a thousand MHCII{beta} alleles and find that many of them covary positively or negatively with parasite load, suggesting that these genes contribute to resistance or susceptibility. However, despite our large sample-size, we find no evidence for the widely-cited stabilizing selection on MHC heterozygosity, in which individuals with an intermediate number of MHC alleles have the lowest parasite burden. Nor do we observe a rare-allele advantage, or widespread fluctuating selection across populations. In contrast, we find that MHC diversity is best predicted by neutral genome-wide heterozygosity and between-population genomic divergence, suggesting neutral processes are important in shaping the pattern of metapopulation MHC diversity. Thus, although MHCII{beta} is highly diverse and relevant to the type and intensity of macroparasite infection in these populations of stickleback, the main models of MHC evolution still provide little explanatory power in this system.

evolutionary biology↗