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Patients undergoing antineoplastic therapies often exhibit reduced immune response to COVID-19 vaccination, necessitating assessment of alternate boosting frequencies for these patients. However, data on reinfection risks to guide clinical decision-making is limited. We quantified reinfection risks of SARS-CoV-2 at different mRNA boosting frequencies of patients on antineoplastic therapies. Antibody levels following Pfizer-BioNTech BNT162b2 vaccination were analyzed for patients without cancer, with cancer undergoing various treatments, and treated with different antineoplastic therapeutics. Using long-term antibody data from other coronaviruses in an evolutionary framework, we estimated infection probabilities based on antibody levels and projected waning. We calculated cumulative probabilities of breakthrough infection for alternate booster schedules over two years. Annual boosting reduced risks for targeted or hormonal treatments, immunotherapy, and chemotherapy-immunotherapy combinations similarly to the general population. Patients receiving no treatment or chemotherapy exhibited higher risks, suggesting that accelerated vaccination schedules should be considered. Patients treated with rituximab therapy posed the highest infection risk, suggesting that a combination of frequent boosting and additional interventions may be warranted for mitigating SARS-CoV-2 infection in these patients.

Since its initial discovery over 50 years ago, understanding the evolution of the vertebrate adaptive immune response has been a major area of research focus for comparative geneticists. However, how the evolutionary novelty of an adaptive immune response impacted the diversity of receptors associated with the innate immune response has received considerably less attention until recently. Here we investigate the diversification of vertebrate Toll-like receptors (TLRs), one of the most ancient and well conserved innate immune receptor families found across the Tree of Life, integrating genomic data that represent all major vertebrate lineages with new transcriptomic data from Polypteriformes, the earliest diverging ray-finned fish lineage. Our analyses reveal TLR sequences that reflect the 6 major TLR subfamilies, TLR1, TLR3, TLR4, TLR5, TLR7, and TLR11, and also currently unnamed, yet phylogenetically distinct TLR clades. We additionally recover evidence for a pulse of gene gain coincident with the rise of the adaptive immune response in jawed vertebrates, followed by a period of rapid gene loss during the Cretaceous. These gene losses are primarily concentrated in marine teleost fish and synchronous with the mid Cretaceous anoxic event, a period of rapid extinction for marine species. Finally, we reveal a mismatch between phylogenetic placement and gene nomenclature for up to 50% of TLRs found in clades such as ray-finned fishes, cyclostomes, amphibians, and elasmobranchs. Collectively these results provide an unparalleled perspective of TLR diversity, and offer a ready framework for testing gene annotations in non-model species.

One of the most consequential unknowns of the COVID-19 pandemic is the frequency at which vaccine boosting provides sufficient protection from infection. We quantified the statistical likelihood of breakthrough infections over time following different boosting schedules with mRNA-1273 (Moderna) and BNT162b2 (Pfizer-BioNTech) by integration of anti-Spike IgG antibody optical densities with profiles of the waning of antibodies and corresponding probabilities of infection associated with endemic transmission. Projecting antibody levels over time given boosting every 6 months, 1 year, 1.5 years, 2 years, or 3 years yielded respective probabilities of fending off infection over a 6-year span of93%, 75%, 55%, 40%, and 24% (mRNA-1273) and89%, 69%, 49%, 36%, and 23% (BNT162b2). Delaying administration of boosters has bleak repercussions regarding the probability of individual infection by SARS-CoV-2, and correspondingly, to the course of ongoing disease spread, prevalence, morbidity, hospitalization, and mortality. Instituting regular, population-wide booster vaccination updated to predominant variants has the potential to substantially forestall-and with widespread uptake, eliminate-COVID-19. This article is protected by copyright. All rights reserved.

The emergence of a new phylogeny of ray-finned fishes at the turn of the twenty-first century marked a paradigm shift in understanding the evolutionary history of half of living vertebrates. We review how the new ray-finned fish phylogeny radically departs from classical expectations based on morphology. We focus on evolutionary relationships that span the backbone of ray-finned fish phylogeny, from the earliest divergences among teleosts and nonteleosts to the resolution of major lineages of Percomorpha. Throughout, we feature advances gained by the new phylogeny toward a broader understanding of ray-finned fish evolutionary history and the implications for topics that span from the genetics of human health to reconsidering the concept of living fossils. Additionally, we discuss conceptual challenges that involve reconciling taxonomic classification with phylogenetic relationships and propose an alternate higher-level classification for Percomorpha. Our review highlights remaining areas of phylogenetic uncertainty and opportunities for comparative investigations empowered by this new phylogenetic perspective on ray-finned fishes.

The ecological theory of adaptive radiation has profoundly shaped our conceptualization of the rules that govern diversification. However, while many radiations follow classic early burst patterns of diversification as they fill ecological space, the longer-term fates of these radiations depend on many factors, such as climatic stability. In systems with periodic disturbances, species-rich clades can contain nested adaptive radiations of subclades with their own distinct diversification histories, and how adaptive radiation theory applies in these cases is less clear. Here, we investigated patterns of ecological and phenotypic diversification within two iterative adaptive radiations of cryonotothenioid fishes in Antarctica’s Southern Ocean: crocodile icefishes and notoperches. For both clades, we observe evidence of repeated diversification into disparate regions of trait space between closely related taxa and into overlapping regions of trait space between distantly related taxa. We additionally find little evidence that patterns of ecological divergence are correlated with evolution of morphological disparity, suggesting that these axes of divergence may not be tightly linked. Finally, we reveal evidence of repeated convergence in sympatry that suggests niche complementarity. These findings reflect the dynamic history of Antarctic marine habitats, and may guide hypotheses of diversification dynamics in environments characterized by periodic disturbance.

Wastewater surveillance is a powerful tool for monitoring the prevalence of infectious disease in urban populations, with predictive value for upcoming increases in cases and hospitalizations. The approach primarily used in disease surveillance has been to measure the number of viral copies detected in wastewater for a study area of known population, and systems for wastewater monitoring have been put in place worldwide during the SARS-CoV-2 pandemic. However, the potential to measure other biomarkers such as proteins and metabolites in wastewater has not been fully explored. Here we develop an approach to determine antibody optical density and titer measurements from wastewater. We measured abundance of anti-SARS-CoV-2 spike IgG and IgA from typical fresh samples of community wastewater, and from a collection of frozen samples dating from 2020-22. The assay described can be performed with readily available commercial reagents, at a moderate per-sample cost, facilitating non-invasive population level immune surveillance. Our findings demonstrate the feasibility of indirect serological surveillance through wastewater for population level monitoring, and the protocol described will enable the collection of larger data sets and development of models that can be leveraged to anticipate public health needs.

Complex patterns of genome and life-history evolution associated with the end-Cretaceous (K– Pg) mass extinction event limit our understanding of the early evolutionary history of crown group birds [1-9]. Here, we assess molecular heterogeneity across living birds using a technique enabling inferred sequence substitution models to transition across the history of a clade [10]. Our approach identifies distinct and contrasting regimes of molecular evolution across exons, introns, untranslated regions, and mitochondrial genomes. Up to fifteen shifts in the mode of avian molecular evolution map to rapidly diversifying clades near the Cretaceous-Palaeogene boundary, demonstrating a burst of genomic disparity early in the evolutionary history of crown birds [11-13]. Using simulation and machine learning techniques, we show that shifts in developmental mode [14] or adult body mass [4] best explain transitions in the mode of nucleotide substitution. These patterns are related, in turn, to macroevolutionary shifts in the allometric scaling relationship between basal metabolic rate and body mass [15, 16]. In agreement with theoretical predictions, this scaling relationship appears to have weakened across the end-Cretaceous transition. Overall, our study provides evidence that the Chicxulub bolide impact [17] triggered integrated patterns of evolution across avian genomes, physiology, and life history that structured the evolutionary potential of modern birds.

Over 99% of ray-finned fishes (Actinopterygii) are teleosts, a clade that comprises half of all living vertebrates that have diversified across virtually all fresh and saltwater ecosystems. This ecological diversity raises the question of how the immunogenetic diversity required to persist under heterogeneous pathogen pressures evolved. The teleost genome duplication (TGD) has been hypothesized as the evolutionary event that provided the genomic substrate for rapid genomic evolution and innovation. However, studies of putative teleost-specific innate immune receptors have been largely limited to comparisons either among teleosts or between teleosts and distantly related vertebrate clades such as tetrapods. Here we describe and characterize the receptor diversity of two clustered innate immune gene families in the teleost sister lineage: Holostei (bowfin and gars). Using genomic and transcriptomic data, we provide a detailed investigation of the phylogenetic history and conserved synteny of gene clusters encoding diverse immunoglobulin domain-containing proteins (DICPs) and novel immune-type receptors (NITRs). These data demonstrate an ancient linkage of DICPs to the major histocompatibility complex (MHC) and reveal an evolutionary origin of NITR variable-joining (VJ) exons that predate the TGD by at least 50 million years. Further characterizing the receptor diversity of Holostean DICPs and NITRs illuminates a sequence diversity that rivals the diversity of these innate immune receptor families in many teleosts. Taken together, our findings provide important historical context for the evolution of these gene families that challenge prevailing expectations concerning the consequences of the TGD during actinopterygiian evolution.

Application of genetic data to species delimitation often builds confidence in delimitations previously hypothesized using morphological, ecological, and geographic data and frequently yields recognition of previously undescribed cryptic diversity. However, a recent critique of genomic data-based species delimitation approaches is that they have the potential to conflate population structure with species diversity, resulting in taxonomic oversplitting. The need for an integrative approach to species delimitation, in which molecular, morphological, ecological, and geographic lines of evidence are evaluated together, is becoming increasingly apparent. Here, we integrate phylogenetic, population genetic, and coalescent analyses of genome-wide sequence data with investigation of variation in multiple morphological traits to delimit species within the Antarctic barbeled plunderfishes (Artedidraconidae: Pogonophryne). Pogonophryne currently comprises 29 valid species, most of which are distinguished solely by variation in the ornamentation of the mental barbel that projects from the lower jaw, a structure previously shown to vary widely within a single species. However, our genomic and phenotypic analyses result in a dramatic reduction in the number of distinct species recognized within the clade, providing evidence to support the recognition of no more than six species. We propose to synonymize 24 of the currently recognized species with five species of Pogonophryne. We find genomic and phenotypic evidence for a new species of Pogonophryne from specimens collected in the Ross Sea. Our findings represent a rare example in which the application of molecular data provides evidence of taxonomic oversplitting on the basis of morphology, clearly demonstrating the utility of an integrative species delimitation framework.[ddRADseq; multispecies coalescent; Notothenioidei; SNPs; Southern Ocean.]

Allopatry has traditionally been viewed as the primary driver of speciation in marine taxa, but the geography of the marine environment and the larval dispersal capabilities of many marine organisms render this view somewhat questionable. In marine fishes, one of the earliest and most highly cited empirical examples of ecological speciation with gene flow is the slippery dick wrasse, Halichoeres bivittatus. Evidence for this cryptic or incipient speciation event was primarily in the form of a deep divergence in a single mitochondrial locus between the northern and southern Gulf of Mexico, combined with a finding that these two haplotypes were associated with different habitat types (“tropical” vs. “subtropical”) in the Florida Keys and Bermuda, where they overlap. Here, we examine habitat assortment in the Florida Keys using a broader sampling of populations and habitat types than were available for the original study. We find no evidence to support the claim that haplotype frequencies differ between habitat types, and little evidence to support any differences between populations in the Keys. These results undermine claims of ecological speciation with gene flow in Halichoeres bivittatus. Future claims of this type should be supported by multiple lines of evidence that illuminate potential mechanisms and allow researchers to rule out alternative explanations for spatial patterns of genetic differences., In this study, we attempt to replicate one of the most highly cited cases of parapatric ecological speciation in marine fishes. Despite having larger sample sizes and a broader sampling of habitats than previous studies, we found no support for ecological speciation or speciation with gene flow.

Evolutionary transitions in water column usage have played a major role in shaping ray-finned fish diversity. However, the extent to which vision-associated trait complexity and water column usage is coupled remains unclear. Here we investigate the relationship between depth niche, eye size, and the molecular basis of light detection across the Antarctic notothenioid adaptive radiation. Using a phylogenetic comparative framework, we integrate sequence analyses of opsin tuning sites with data on eye size and depth occupancy from over two decades of NOAA trawl-based surveys. We find a consistent signature of changes in tuning sites suggestive of shifts in their ability to detect lower wavelengths of light. These represent repeated instances of independent tuning site changes across the notothenioid phylogeny that are generally not associated with habitat depth or species eye size. We further reveal an acceleration in the rate of eye size diversification nearly 20 million years after the initial radiation that has manifested in high levels of eye size divergence among closely related taxa. Collectively, our results strongly support a decoupling of the diversification dynamics between opsin tuning sites, eye size and depth, providing a new perspective of the evolution of the visual system in this iconic adaptive radiation.

The durability of vaccine-mediated immunity to SARS-CoV-2, the durations to breakthrough infection, and the optimal timings of booster vaccination are crucial knowledge for pandemic response. Here, we applied comparative evolutionary analyses to estimate the durability of immunity and the likelihood of breakthrough infections over time following vaccination by BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), ChAdOx1 (Oxford-AstraZeneca), and Ad26.COV2.S (Johnson & Johnson/Janssen). We evaluated anti-Spike (S) immunoglobulin G (IgG) antibody levels elicited by each vaccine relative to natural infection. We estimated typical trajectories of waning and corresponding infection probabilities, providing the distribution of times to breakthrough infection for each vaccine under endemic conditions. Peak antibody levels elicited by messenger RNA (mRNA) vaccines mRNA-1273 and BNT1262b2 exceeded that of natural infection and are expected to typically yield more durable protection against breakthrough infections (median 29.6 mo; 5 to 95% quantiles 10.9 mo to 7.9 y) than natural infection (median 21.5 mo; 5 to 95% quantiles 3.5 mo to 7.1 y). Relative to mRNA-1273 and BNT1262b2, viral vector vaccines ChAdOx1 and Ad26.COV2.S exhibit similar peak anti-S IgG antibody responses to that from natural infection and are projected to yield lower, shorter-term protection against breakthrough infection (median 22.4 mo and 5 to 95% quantiles 4.3 mo to 7.2 y; and median 20.5 mo and 5 to 95% quantiles 2.6 mo to 7.0 y; respectively). These results leverage the tools from evolutionary biology to provide a quantitative basis for otherwise unknown parameters that are fundamental to public health policy decision-making.

Multiple novel immunoglobulin-like transcripts (NILTs) have been identified from salmon, trout and carp. NILTs typically encode activating or inhibitory transmembrane receptors with extracellular immunoglobulin (Ig) domains. Although predicted to provide immune recognition in ray-finned fish, we currently lack a definitive framework of NILT diversity, thereby limiting our predictions for their evolutionary origin and function. In order to better understand the diversity of NILTs and their possible roles in immune function, we identified five NILT loci in the Atlantic salmon (Salmo salar) genome, defined 86 NILT Ig domains within a 3 Mbp region of zebrafish (Danio rerio) chromosome 1, and described 41 NILT Ig domains as part of an alternative haplotype for this same genomic region. We then identified transcripts encoded by 43 different NILT genes which reflect an unprecedented diversity of Ig domain sequences and combinations for a family of non-recombining receptors within a single species. Zebrafish NILTs include a sole putative activating receptor but extensive inhibitory and secreted forms as well as membrane-bound forms with no known signaling motifs. These results reveal a higher level of genetic complexity, interindividual variation and sequence diversity for NILTs than previously described, suggesting that this gene family likely plays multiple roles in host immunity.

Briefly considered extinct in the wild, the future of the wild population of the Wyoming toad (Anaxyrus baxteri) continues to rely on captive breeding to supplement the wild population. Given its small natural geographic range and history of rapid population decline at least partly due to fungal disease, investigation of the diversity of key receptor families involved in the host immune response represents an important conservation need. Population decline may have reduced immunogenetic diversity sufficiently to increase the vulnerability of the species to infectious diseases. Here we use comparative transcriptomics to examine the diversity of toll-like receptors and major histocompatibility complex (MHC) sequences across three individual Wyoming toads. We find reduced diversity at MHC genes compared to bufonid species with a similar history of bottleneck events. Our data provide a foundation for future studies that seek to evaluate the genetic diversity of Wyoming toads, identify biomarkers for infectious disease outcomes, and guide breeding strategies to increase genomic variability and wild release successes.

ImportanceSuccessive waves of infection by SARS-CoV-2 have left little doubt that COVID-19 will transition to an endemic disease, yet the future seasonality of COVID-19 remains one of its most consequential unknowns. Foreknowledge of spatiotemporal surges would have immediate and long-term consequences for medical and public health decision-making.ObjectiveTo estimate the impending endemic seasonality of COVID-19 in temperate population centers via a phylogenetic ancestral and descendent states approach that leverages long-term data on the incidence of circulating coronaviruses.DesignWe performed a comparative evolutionary analysis on literature-based monthly verified cases of HCoV-NL63, HCoV-229E, HCoV-HKU1, and HCoV-OC43 infection within populations across the Northern Hemisphere. Ancestral and descendent states analyses on human-infecting coronaviruses provided projections of the impending seasonality of endemic COVID-19.SettingQuantitative projections of the endemic seasonality of COVID-19 were based on human endemic coronavirus infection incidence data from New York City (USA); Denver (USA); Tampere (Finland); Trøndelag (Norway); Gothenburg (Sweden); Stockholm (Sweden); Amsterdam (Netherlands); Beijing (China); South Korea (Nationwide); Yamagata (Japan); Hong Kong; Nakon Si Thammarat (Thailand); Guangzhou (China); and Sarlahi (Nepal).Main Outcome(s) and Measure(s)The primary projection was the monthly relative frequency of SARS-CoV-2 infections in each geographic locale. Four secondary outcomes consisted of empirical monthly relative frequencies of the endemic human-infecting coronaviruses HCoV-NL63, -229E, -HKU1, and -OC43.ResultsWe project asynchronous surges of SARS-CoV-2 across locales in the Northern Hemisphere. In New York City, SARS-CoV-2 incidence is projected in late fall and winter months (Nov.–Jan.), In Tampere, Finland; Yamagata, Japan; and Sarlahi, Nepal incidence peaks in February. Gothenburg and Stockholm in Sweden reach peak incidence between November and February. Guangzhou, China; and South Korea. In Denver, incidence peaks in early Spring (Mar.). In Amsterdam, incidence rises in late fall (Dec.), and declines in late spring (Apr.). In Hong Kong, the projected apex of infection is in late fall (Nov.–Dec.), yet variation in incidence is muted across other seasons. Seasonal projections for Nakhon Si Thammarat, Thailand and for Beijing, China are muted compared to other locations.Conclusions and RelevanceThis knowledge of likely spatiotemporal surges of COVID-19 is fundamental to medical preparedness and expansions of public health interventions that anticipate the impending endemicity of this disease and mitigate COVID-19 transmission. These results provide crucial guidance for adaptive public health responses to this disease, and are vital to the long-term mitigation of COVID-19 transmission.Key PointsQuestionUnder endemic conditions, what are the projected spatiotemporal seasonal surges of COVID-19?FindingsWe applied a phylogenetic ancestral and descendent states approach, leveraging long-term data on the incidence of circulating coronaviruses. We found that seasonal surges are expected in or near the winter months; dependent on the specific population center, infections are forecasted to surge in the late fall, winter, or early spring.MeaningGlobally, endemic COVID-19 surges should be expected to occur asynchronously, often coincident with local expected surges of other human-infecting respiratory viruses.

Across the Tree of Life, most studies of phenotypic disparity and diversification have been restricted to adult organisms. However, many lineages have distinct ontogenetic phases that do not reflect the same traits as their adult forms. Non-adult disparity patterns are particularly important to consider for coastal ray-finned fishes, which often have juvenile phases with distinct phenotypes. These juvenile forms are often associated with sheltered nursery environments, with phenotypic shifts between adults and juvenile stages that are readily apparent in locomotor morphology. However, whether this ontogenetic variation in locomotor morphology reflects a decoupling of diversification dynamics between life stages remains unknown. Here we investigate the evolutionary dynamics of locomotor morphology between adult and juvenile triggerfishes. Integrating a time-calibrated phylogenetic framework with geometric morphometric approaches and measurement data of fin aspect ratio and incidence, we reveal a mismatch between morphospace occupancy, the evolution of morphological disparity, and the tempo of trait evolution between life stages. Collectively, our results illuminate how the heterogeneity of morpho-functional adaptations can decouple the mode and tempo of morphological diversification between ontogenetic stages.

Summary Background Among the most consequential unknowns of the devastating COVID-19 pandemic are the durability of immunity and time to likely reinfection. There are limited direct data on SARS-CoV-2 long-term immune responses and reinfection. The aim of this study is to use data on the durability of immunity among evolutionarily close coronavirus relatives of SARS-CoV-2 to estimate times to reinfection by a comparative evolutionary analysis of related viruses SARS-CoV, MERS-CoV, human coronavirus (HCoV)-229E, HCoV-OC43, and HCoV-NL63. Methods We conducted phylogenetic analyses of the S, M, and ORF1b genes to reconstruct a maximum-likelihood molecular phylogeny of human-infecting coronaviruses. This phylogeny enabled comparative analyses of peak-normalised nucleocapsid protein, spike protein, and whole-virus lysate IgG antibody optical density levels, in conjunction with reinfection data on endemic human-infecting coronaviruses. We performed ancestral and descendent states analyses to estimate the expected declines in antibody levels over time, the probabilities of reinfection based on antibody level, and the anticipated times to reinfection after recovery under conditions of endemic transmission for SARS-CoV-2, as well as the other human-infecting coronaviruses. Findings We obtained antibody optical density data for six human-infecting coronaviruses, extending from 128 days to 28 years after infection between 1984 and 2020. These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans (5–95% quantiles 15 months to 10 years for HCoV-OC43, 31 months to 12 years for HCoV-NL63, and 16 months to 12 years for HCoV-229E). For SARS-CoV, the 5–95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset. Interpretation The timeframe for reinfection is fundamental to numerous aspects of public health decision making. As the COVID-19 pandemic continues, reinfection is likely to become increasingly common. Maintaining public health measures that curb transmission—including among individuals who were previously infected with SARS-CoV-2—coupled with persistent efforts to accelerate vaccination worldwide is critical to the prevention of COVID-19 morbidity and mortality. Funding US National Science Foundation.

The bowfin (Amia calva) is a ray-finned fish that possesses a unique suite of ancestral and derived phenotypes, which are key to understanding vertebrate evolution. The phylogenetic position of bowfin as a representative of neopterygian fishes, its archetypical body plan and its unduplicated and slowly evolving genome make bowfin a central species for the genomic exploration of ray-finned fishes. Here we present a chromosome-level genome assembly for bowfin that enables gene-order analyses, settling long-debated neopterygian phylogenetic relationships. We examine chromatin accessibility and gene expression through bowfin development to investigate the evolution of immune, scale, respiratory and fin skeletal systems and identify hundreds of gene-regulatory loci conserved across vertebrates. These resources connect developmental evolution among bony fishes, further highlighting the bowfin’s importance for illuminating vertebrate biology and diversity in the genomic era., Analysis of a chromosome-level bowfin genome assembly sheds light into neopterygian fish evolution. Chromatin accessibility and gene expression profiling provides insight into bowfin embryonic development.

The progression of cancer is an evolutionary process that is challenging to assess between sampling timepoints. However, investigation of cancer evolution over specific time periods is crucial to the elucidation of key events such as the acquisition of therapeutic resistance and subsequent fatal metastatic spread of therapy-resistant cell populations. Here we apply mutational signature analyses within clinically annotated cancer chronograms to detect and describe the shifting mutational processes caused by both endogenous (e.g. mutator gene mutation) and exogenous (e.g. mutagenic therapeutics) factors between tumor sampling timepoints. In one patient, we find that cisplatin therapy can introduce mutations that confer genetic resistance to subsequent targeted therapy with Erlotinib. In another patient, we trace detection of defective mismatch-repair associated mutational signature SBS3 to the emergence of known driver mutation CTNNB1 S37C. In both of these patients, metastatic lineages emerged from a single ancestral lineage that arose during therapy—a finding that argues for the consideration of local consolidative therapy over other therapeutic approaches in EGFR-positive non-small cell lung cancer. Broadly, these results demonstrate the utility of phylogenetic analysis that incorporates clinical time course and mutational signature deconvolution to inform therapeutic decision making and retrospective assessment of disease etiology.

Spiny-rayed fishes (Acanthomorpha) dominate modern marine habitats and comprise more than a quarter of all living vertebrate species1–3. It is believed that this dominance resulted from explosive lineage and phenotypic diversification coincident with the Cretaceous-Paleogene (K-Pg) mass-extinction event4. It remains unclear, however, if living acanthomorph diversity is the result of a punctuated burst or gradual accumulation of diversity following the K-Pg. We assess these hypotheses with a time-calibrated phylogeny inferred using ultraconserved elements from a sampling of species that represent over 91% of all acanthomorph families, as well as an extensive body shape dataset of extant species. Our results indicate that several million years after the end-Cretaceous, acanthomorphs underwent a prolonged and significant expansion of morphological disparity primarily driven by changes in body elongation, and that acanthomorph lineages containing the bulk of the living species diversity originated throughout the Cenozoic. These acanthomorph lineages radiated into distinct regions of morphospace and retained their iconic phenotypes, including a large group of laterally compressed reef fishes, fast-swimming open-ocean predators, bottom-dwelling flatfishes, seahorses, and pufferfishes. The evolutionary success of spiny-rayed fishes is the culmination of a post K-Pg adaptive radiation in which rates of lineage diversification were decoupled from periods of high phenotypic disparity.

Cancer progression is an evolutionary process. During this process, evolving cancer cell populations encounter restrictive ecological niches within the body, such as the primary tumor, circulatory system, and diverse metastatic sites. Efforts to prevent or delay cancer evolution—and progression—require a deep understanding of the underlying molecular evolutionary processes. Herein we discuss a suite of concepts and tools from evolutionary and ecological theory that can inform cancer biology in new and meaningful ways. We also highlight current challenges to applying these concepts, and propose ways in which incorporating these concepts could identify new therapeutic modes and vulnerabilities in cancer.

Leeches (Hirudinida) comprise a charismatic, yet often maligned group of organisms. Despite their ecological, economic, and medical importance, a general consensus on the phylogenetic relationships of major hirudinidan lineages is lacking. This absence of a consistent, robust phylogeny of early-diverging lineages has hindered our understanding of the underlying processes that enabled evolutionary diversification of this clade. Here, we used an anchored hybrid enrichment-based phylogenomic approach, capturing hundreds of loci to investigate phylogenetic relationships among major hirudinidan lineages and their closest living relatives. Our results suggest that a dramatic reinterpretation of early leech evolution is warranted. We recovered Branchiobdellida as sister to a clade that includes all major lineages of hirudinidans, but found Acanthobdella to be nested within Oceanobdelliformes. These results cast doubt on the utility of Acanthobdella as a “missing link” used to explain the origin of blood-feeding in hirudineans. Further, our results support a deep divergence between predominantly marine and freshwater lineages, while not supporting the reciprocal monophyly of jawed and proboscis-bearing leeches. To sum up, our phylogenomic resolution of early-diverging leeches provides a necessary foundation for illuminating the evolution of host–symbiont associations and key adaptations that have allowed leeches to colonize a wide diversity of habitats worldwide.

A major emerging challenge to resolution of a stable phylogenetic Tree of Life has been incongruent inference among studies. Given the increasing ubiquity of incongruent studies, analyzing the predicted phylogenetic utility and quantitative evidence regarding contributions toward resolution of commonly-used markers in historical studies over the last decade represents an important, yet neglected, component of phylogenetics. Here we examine the phylogenetic utility of two sets of commonly-used legacy markers for understanding the evolutionary relationships among goodeines, a group of viviparous freshwater fishes endemic to central Mexico. Our analyses reveal that the validity of existing inferences is compromised by both lack of information and substantially biased patterns of nucleotide substitution. Our analyses demonstrate that many of the evolutionary relationships of goodeines remain uncertain – despite over a century of work. Our results provide an updated baseline of critically needed areas of investigation for the group and underscore the importance of quantifying phylogenetic information content as a fundamental step towards eroding false confidence in results based on weak and biased evidence.

Notothenioids are among the most intensively studied lineages of marine fishes. However, notothenioid research is predominately focused on the approximately 100 species of Antarctic cryonotothenioids. Far less attention is devoted to the non-Antarctic lineages Bovichtidae, Pseudaphritis urvillii, and Eleginops maclovinus, all of which originated prior to the diversification of cryonotothenioid species. Here we utilize DNA sequence data from mitochondrial and nuclear genes, as well as meristic trait morphology to investigate the evolutionary history of Bovichtidae. Bovichtus is the only polytypic lineage of early diverging non-Antarctic notothenioids providing a unique opportunity to contextualize the diversification dynamics of cryonotothenioids with their non-Antarctic relatives. We find strong evidence that species of Bovichtus represent a recent evolutionary radiation with divergence times similar to those estimated among the most closely related species of cryonotothenioids. The divergence in traditional meristic trait morphology among species of Bovichtus is consistent with their phylogenetic relationships. The phylogeny of Bovichtus implies the wide geographic distribution of species in the clade is likely the result of West Wind drift-driven dispersal. The phylogeny and divergence time estimates results reject a hypothesis that species persistence in Bovichtus reflects long periods of evolutionary stasis. Instead, we hypothesize that patterns of extinction and diversification in Bovichtus closely mirror those observed in their Antarctic relatives.

Spiny-rayed fishes (Acanthomorpha) dominate modern marine habitats and account for more than a quarter of all living vertebrate species. Previous time-calibrated phylogenies and patterns from the fossil record explain this dominance by correlating the origin of major acanthomorph lineages with the Cretaceous-Palaeogene mass extinction. Here we infer a time-calibrated phylogeny using ultraconserved elements that samples 91.4% of all acanthomorph families and investigate patterns of body shape disparity. Our results show that acanthomorph lineages steadily accumulated throughout the Cenozoic and underwent a significant expansion of among-clade morphological disparity several million years after the end-Cretaceous. These acanthomorph lineages radiated into and diversified within distinct regions of morphospace that characterize iconic lineages, including fast-swimming open-ocean predators, laterally compressed reef fishes, bottom-dwelling flatfishes, seahorses and pufferfishes. The evolutionary success of spiny-rayed fishes is the culmination of multiple species-rich and phenotypically disparate lineages independently diversifying across the globe under a wide range of ecological conditions.

The progression of cancer—including the acquisition of therapeutic resistance and the fatal metastatic spread of therapy-resistant cell populations—is an evolutionary process that is challenging to monitor between sampling timepoints. Here we apply mutational signature analysis to clinically correlated cancer chronograms to detect and describe the shifting mutational processes caused by both endogenous (e.g. mutator mutation) and exogenous (e.g. therapeutic) factors between tumor sampling timepoints. In one patient, we find that cisplatin therapy can introduce mutations that increase the likelihood of genetic adaptation to subsequent targeted therapeutics. In another patient, we trace the emergence of known driver mutation CTNNB1 S37C to specific detection of defective mismatch repair associated mutational signature SBS3. Metastatic lineages were found to emerge from a single ancestral lineage arising during therapy—a finding that argues for the consideration of local consolidative therapy over other therapeutic approaches in EGFR-positive non-small cell lung cancer. Broadly, these results demonstrate the utility of phylogenetic analysis that incorporates clinical time course and mutational signature detection to inform clinical decision making and retrospective assessment of disease etiology.

Understanding the role of ecological processes in speciation has become one of the most active areas of research in marine population biology in recent decades. The traditional view was that allopatry was the primary driver of speciation in marine taxa, but the geography of the marine environment and the dispersal capabilities of many marine organisms render this view somewhat questionable. One of the earliest and most highly cited empirical examples of ecological speciation with gene flow in marine fishes is that of the slippery dick wrasse, Halichoeres bivittatus. Evidence for this cryptic or incipient speciation event was primarily in the form of a deep north-south divergence in a single mitochondrial locus, combined with a finding that these two haplotypes were associated with different habitat types in the Florida Keys and Bermuda, where they overlap. Here we examine habitat assortment in the Florida Keys using a broader sampling of populations and habitat types than were available for the original study, and find no evidence to support the claim that haplotype frequencies differ between habitat types, and little evidence to support any differences between populations. These results severely undermine claims of ecological speciation with gene flow in Halichoeres bivittatus. We argue that future claims of this type should be supported by multiple lines of evidence that illuminate potential mechanisms and allow researchers to rule out alternative explanations for spatial patterns of genetic differences.

1. Species distribution models (SDMs) are frequently used to predict the effects of climate change on species of conservation concern. Biases inherent in the process of constructing SDMs and transferring them to new climate scenarios may result in undesirable conservation outcomes. We explore these issues and demonstrate new methods to estimate biases induced by the design of SDM studies. We present these methods in the context of estimating the effects of climate change on Australia's only endemic Pokémon.2. Using a citizen science dataset, we build species distribution models for Garura kangaskhani to predict the effects of climate change on the suitability of habitat for the species. We demonstrate a novel Monte Carlo procedure for estimating the biases implicit in a given study design, and compare the results seen for Pokémon to those seen from our Monte Carlo tests as well as previous studies in the same region using both simulated and real data.3. Our models suggest that climate change will impact the suitability of habitat for G. kangaskhani, which may compound the effects of threats such as habitat loss and their use in blood sport. However, we also find that using SDMs to estimate the effects of climate change can be accompanied by biases so strong that the data themselves have minimal impact on modelling outcomes. 4. We show that the direction and magnitude of bias in estimates of climate change impacts are affected by every aspect of the modelling process, and suggest that bias estimates should be included in future studies of this type. Given the widespread use of SDMs, systemic biases could have substantial financial and opportunity costs. By demonstrating these biases and presenting a novel statistical tool to estimate them, we hope to provide a more secure future for G. kangaskhani and the rest of the world's biodiversity.

Comparative genomic analyses have enormous potential for identifying key genes central to human health phenotypes, including those that promote cancers. In particular, the successful development of novel therapeutics using model species requires phylogenetic analyses to determine molecular homology. Accordingly, we investigate the evolutionary histories of anaplastic lymphoma kinase (ALK)—which can underlie tumorigenesis in neuroblastoma, nonsmall cell lung cancer, and anaplastic large-cell lymphoma—its close relative leukocyte tyrosine kinase (LTK) and their candidate ligands. Homology of ligands identified in model organisms to those functioning in humans remains unclear. Therefore, we searched for homologs of the human genes across metazoan genomes, finding that the candidate ligands Jeb and Hen-1 were restricted to nonvertebrate species. In contrast, the ligand augmentor (AUG) was only identified in vertebrates. We found two ALK-like and four AUG-like protein-coding genes in lamprey. Of these six genes, only one ALK-like and two AUG-like genes exhibited early embryonic expression that parallels model mammal systems. Two copies of AUG are present in nearly all jawed vertebrates. Our phylogenetic analysis strongly supports the presence of previously unrecognized functional convergences of ALK and LTK between actinopterygians and sarcopterygians—despite contemporaneous, highly conserved synteny of ALK and LTK. These findings provide critical guidance regarding the propriety of fish and mammal models with regard to model organism-based investigation of these medically important genes. In sum, our results provide the phylogenetic context necessary for effective investigations of the functional roles and biology of these critically important receptors.

The bowfin fish (Amia calva) diverged before the genome duplication in teleost fishes, and its archetypical body plan and slow rate of molecular evolution make it a key species for genomic exploration as a basal representative of the neopterygian fishes. To investigate the evolution and development of ray-finned fishes, we generated a chromosome-level genome assembly for bowfin that enables gene-order analyses which settle its long-debated, phylogenetic relationship with gars. We analyze the genomic underpinnings of the bowfin’s unique combination of derived and ancestral phenotypes involving the immune system as well as scale, respiratory organ, and skeletal development. By detailing chromatin accessibility and gene expression through bowfin development, we connect developmental gene regulatory loci across vertebrates. We illustrate the utility of these genomic resources to connect developmental evolution across bony fishes, showing the importance of bowfin in understanding vertebrate biology and diversity.

Hemidactylus spp. (House geckos) rank among the most successful invasive reptile species worldwide. Hemidactylus mabouia in particular has become ubiquitous across tropical urban settings in the Western Hemisphere. H. mabouia’s ability to thrive in close proximity to humans has led to the rapid displacement of native geckos in urban areas, however the mechanisms driving this displacement remain understudied. Here we combine data from nitrogen and carbon stable isotopes, stomach contents, and morphometric analyses of traits associated with feeding and locomotion to test alternate hypotheses of displacement between H. mabouia and a native gecko, Phyllodactylus martini, on the island of Curaçao. Consistent with expectations of direct food resource competition, we demonstrate substantial overlap of invertebrate prey resources between the species. Additionally, we found strong evidence from both diet content and stable isotope analyses that H. mabouia acts as a vertebrate predator, preying upon P. martini as well as other native and non-native reptiles. Finally, we show that H. mabouia possesses several morphological advantages, including larger sizes in feeding-associated traits and limb proportions that could offer a propulsive locomotor advantage on vertical surfaces. Together, these findings suggest the successful establishment of H. mabouia likely involves a combination of both exploitative interspecific competition and predation. Given the ubiquity of H. mabouia, illuminating the role of this species as both a competitor and a predator casts new concerns on the ecological and demographic impacts of this widespread urban invader.

An understanding of host-parasite interactions represents an important, but often overlooked, axis for predicting how marine biodiversity may be impacted by continued environmental change over the next century. For host and parasite communities in the Southern Ocean, investigations of many major groups of parasites have largely been limited to taxonomic and phylogenetic studies, creating an urgent need for the collection of baseline ecological data if we are to detect changes in host-parasite interactions in the future. Here, we survey three species of Crocodile icefish (Notothenioidei: Channichthyidae) collected from two island archipelagos in Antarctica’s South Scotia Arc region for evidence of leech infestations. Specifically, we report on infestation prevalence and intensity of three leech species (Trulliobdella bacilliformis, Trulliobdella capitis, and Nototheniobdella sawyeri) on the host fish species Chaenocephalus aceratus, Champsocephalus gunnari, and Chionodraco rastrospinosus. Additionally, we characterize spatial patterns of relative abundances of each leech species across the Elephant and South Orkney Islands, size distribution of parasitized fish, and patterns of host and attachment site specificity. Our results reveal high levels of attachment area fidelity for each leech species. These results suggest skin thickness and density of the vascular network constrain leech attachment sites and further suggest trophic transmission to be an important axis of parasitization. We also demonstrate that, while leech species appear to be clustered spatially, this clustering does not appear to be correlated with fish biomass. This study illuminates the complex interactions among fish hosts and leech parasites in the Southern Ocean and lays the groundwork for future studies of Antarctic marine leech ecology that can aid in forecasting how host-parasite interactions may shift in the face of ongoing climate change., Sí

With the rise of genome-scale data sets, there has been a call for increased data scrutiny and careful selection of loci that are appropriate to use in an attempt to resolve a phylogenetic problem. Such loci should maximize phylogenetic information content while minimizing the risk of homoplasy. Theory posits the existence of characters that evolve at an optimum rate, and efforts to determine optimal rates of inference have been a cornerstone of phylogenetic experimental design for over two decades. However, both theoretical and empirical investigations of optimal rates have varied dramatically in their conclusions: spanning no relationship to a tight relationship between the rate of change and phylogenetic utility. Herein, we synthesize these apparently contradictory views, demonstrating both empirical and theoretical conditions under which each is correct. We find that optimal rates of characters-not genes-are generally robust to most experimental design decisions. Moreover, consideration of site rate heterogeneity within a given locus is critical to accurate predictions of utility. Factors such as taxon sampling or the targeted number of characters providing support for a topology are additionally critical to the predictions of phylogenetic utility based on the rate of character change. Further, optimality of rates and predictions of phylogenetic utility are not equivalent, demonstrating the need for further development of comprehensive theory of phylogenetic experimental design. [Divergence time; GC bias; homoplasy; incongruence; information content; internode length; optimal rates; phylogenetic informativeness; phylogenetic theory; phylogenetic utility; phylogenomics; signal and noise; subtending branch length; state space; taxon and character sampling.].

Understanding how organismal design evolves in response to environmental challenges is a central goal of evolutionary biology. In particular, assessing the extent to which environmental requirements drive general design features among distantly related groups is a major research question. The visual system is a critical sensory apparatus that evolves in response to changing light regimes. In vertebrates, the optic tectum is the primary visual processing centre of the brain and yet it is unclear how or whether this structure evolves while lineages adapt to changes in photic environment. On one hand, dim-light adaptation is associated with larger eyes and enhanced light-gathering power that could require larger information processing capacity. On the other hand, dim-light vision may evolve to maximize light sensitivity at the cost of acuity and colour sensitivity, which could require less processing power. Here, we use X-ray microtomography and phylogenetic comparative methods to examine the relationships between diel activity pattern, optic morphology, trophic guild and investment in the optic tectum across the largest radiation of vertebrates-teleost fishes. We find that despite driving the evolution of larger eyes, enhancement of the capacity for dim-light vision generally is accompanied by a decrease in investment in the optic tectum. These findings underscore the importance of considering diel activity patterns in comparative studies and demonstrate how vision plays a role in brain evolution, illuminating common design principles of the vertebrate visual system.

Trade‐offs associated with sexual size dimorphism (SSD) are well documented across the Tree of Life. However, studies of SSD often do not consider potential investment trade‐offs between metabolically expensive structures under sexual selection and other morphological modules. Based on the expectations of the expensive tissue hypothesis, investment in one metabolically expensive structure should come at the direct cost of investment in another. Here, we examine allometric trends in the ontogeny of oyster toadfish (Opsanus tau) to test whether investment in structures known to have been influenced by strong sexual selection conform to these expectations. Despite recovering clear changes in the ontogeny of a sexually selected trait between males and females, we find no evidence for predicted ontogenetic trade‐offs with metabolically expensive organs. Our results are part of a growing body of work demonstrating that increased investment in one structure does not necessarily drive a wholesale loss of mass in one or more organs.