Search

Summary Following antigen encounter, immunoglobulin genes are diversified by somatic hypermutation. The mechanism by which this mutational process preferentially targets immunoglobulin genes is not known, but is likely linked to transcription. However, transcription is not sufficient to ensure mutability. Here, by polymerase chain reaction amplification of bisulfite-modified DNA, the pattern of demethylation within the Igκ mutation domain is analysed and transgenes are used to identify an association between demethylation and mutability. In mice carrying an Igκ transgene that is well transcribed but only poorly targeted for hypermutation, the mutated transgene copies have been demethylated within the mutation domain, whereas the methylated copies remain unmutated. Thus, the hypermutation mechanism only acts on immunoglobulin gene targets that are demethylated as well as transcribed, although transcription and demethylation do not themselves guarantee mutability. [ABSTRACT FROM AUTHOR]

Earth's old animals are in decline. Despite this, emerging research is revealing the vital contributions of older individuals to cultural transmission, population dynamics, and ecosystem processes and services. Often the largest and most experienced, old individuals are most valued by humans and make important contributions to reproduction, information acquisition and cultural transmission, trophic dynamics, and resistance and resilience to natural and anthropogenic disturbance. These observations contrast with the senescence-focused paradigm of old age that has dominated the literature for over a century yet are consistent with findings from behavioral ecology and life-history theory. Here, we review why the global loss of old individuals can be particularly detrimental to long-lived animals with indeterminate growth, increasing reproductive output with age, and those dependent on migration, sociality and cultural transmission for survival. Longevity conservation is needed to protect the important ecological roles an ecosystem services provided by old animals.

With large wildfires becoming more frequent 1,2 , we must rapidly learn how megafires impact biodiversity to prioritize mitigation and improve policy. A key challenge is to discover how interactions among fire-regime components, drought and land tenure shape wildfire impacts. The globally unprecedented 3,4 2019-2020 Australian megafires burnt more than 10 million hectares 5 , prompting major investment in biodiversity monitoring. Collated data include responses of more than 2,000 taxa, providing an unparalleled opportunity to quantify how megafires affect biodiversity. We reveal that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas. Areas burnt at high severity, outside protected areas or under extreme drought also had larger effects. The effects included declines and increases after fire, with the largest responses in rainforests and by mammals. Our results implicate species interactions, dispersal and extent of in situ survival as mechanisms underlying fire responses. Building wildfire resilience into these ecosystems depends on reducing fire recurrence, including with rapid wildfire suppression in areas frequently burnt. Defending wet ecosystems, expanding protected areas and considering localized drought could also contribute. While these countermeasures can help mitigate the impacts of more frequent megafires, reversing anthropogenic climate change remains the urgent broad-scale solution., Competing Interests: Competing interests The authors declare that some of them work for government agencies involved in forestry and implementing planned burns (Supplementary Table 8). The lead author declares that, despite the potential for government agencies to impose policy positions on staff communications (see ref. 51), scientific independence and integrity has been maintained throughout this project., (© 2024. The Author(s).)

As urbanization expands globally, human-wildlife interactions will inevitably increase. Here, we analysed 10 years of wildlife rehabilitation records of squamate (snake and lizard) reptiles ( n = 37 075) from the Greater Sydney region, New South Wales, Australia, to explore their value to address management and conservation issues. Rescues were highly non-random regarding taxonomic focus, spatial occurrences and temporal trends due to the combined influence of (i) reptile phenology and behaviour and (ii) human perceptions of reptiles. Seasonal peaks in rescues reflect reptile and, to a lesser extent, human activity. Spatial patterns of rescues were informative about distributions and presence of easily identified taxa but were primarily driven by human presence. Larger squamate species were rescued more frequently, potentially reflecting a perception of greater danger or rescue priority. While uncommon species were often misidentified, accurate reports of these taxa may guide targeted surveys. The value of these data for conservation and management could be enhanced by emphasizing reptile identification training of volunteers and use of applications for informed species identification. Wildlife rehabilitation data offer a cost-effective means of quantifying thousands of human-reptile interactions, identifying foci (in both time and space) of human-wildlife conflict such as snakebite risk and roadkill-related reptile mortality., Competing Interests: We declare we have no competing interests., (© 2024 The Authors.)

Hypomethylating agents (HMAs) are frontline therapies for Myelodysplastic Neoplasms (MDS) and Acute Myeloid Leukemia (AML). However, acquired resistance and treatment failure are commonplace. To address this, we perform a genome-wide CRISPR-Cas9 screen in a human MDS-derived cell line, MDS-L, and identify TOPORS as a loss-of-function target that synergizes with HMAs, reducing leukemic burden and improving survival in xenograft models. We demonstrate that depletion of TOPORS mediates sensitivity to HMAs by predisposing leukemic blasts to an impaired DNA damage response (DDR) accompanied by an accumulation of SUMOylated DNMT1 in HMA-treated TOPORS-depleted cells. The combination of HMAs with targeting of TOPORS does not impair healthy hematopoiesis. While inhibitors of TOPORS are unavailable, we show that inhibition of protein SUMOylation with TAK-981 partially phenocopies HMA-sensitivity and DDR impairment. Overall, our data suggest that the combination of HMAs with inhibition of SUMOylation or TOPORS is a rational treatment option for High-Risk MDS (HR-MDS) or AML., (© 2024. The Author(s).)

Ecosystem engineers modify their environment and influence the availability of resources for other organisms. Burrowing species, a subset of allogenic engineers, are gaining recognition as ecological facilitators. Burrows created by these species provide habitat for a diverse array of other organisms. Following disturbances, burrows could also serve as ecological refuges, thereby enhancing ecological resistance to disturbance events. We explored the ecological role of Common Wombat ( Vombatus ursinus ) burrows using camera traps in forests of southeastern Australia. We compared animal activity at paired sites with and without burrows, from the same fire severity class and habitat. We examined how animal activity at Common Wombat burrows was affected by the 2019-20 Black Summer bushfires in Australia. We predicted that burrows would serve as hotspots for animal activity and as refuges in burned areas. The activity of several species including Bush Rat ( Rattus fuscipes ), Agile Antechinus ( Antechinus agilis ), Lace Monitor ( Varanus varius ), Painted Button-quail ( Turnix varius ), and Grey Shrike-thrush ( Colluricincla harmonica ) increased at sites where Common Wombat burrows were present, while other species avoided burrows. Species that were more active at burrows tended to be smaller mammal and bird species that are vulnerable to predation, whereas species that avoided burrows tended to be larger mammals that might compete with Common Wombat for resources. Species composition differed between sites with and without burrows, and burrow sites had higher native mammal species richness. The association of several species with burrows persisted or strengthened in areas that burned during the 2019-20 Black Summer bushfires, suggesting that Common Wombat burrows may act as ecological refuges for animals following severe wildfire. Our findings have relevance for understanding how animals survive, persist, and recover following extreme wildfire events., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society of Mammalogists.)

Noncoding DNA is central to our understanding of human gene regulation and complex diseases 1,2 , and measuring the evolutionary sequence constraint can establish the functional relevance of putative regulatory elements in the human genome 3-9 . Identifying the genomic elements that have become constrained specifically in primates has been hampered by the faster evolution of noncoding DNA compared to protein-coding DNA 10 , the relatively short timescales separating primate species 11 , and the previously limited availability of whole-genome sequences 12 . Here we construct a whole-genome alignment of 239 species, representing nearly half of all extant species in the primate order. Using this resource, we identified human regulatory elements that are under selective constraint across primates and other mammals at a 5% false discovery rate. We detected 111,318 DNase I hypersensitivity sites and 267,410 transcription factor binding sites that are constrained specifically in primates but not across other placental mammals and validate their cis-regulatory effects on gene expression. These regulatory elements are enriched for human genetic variants that affect gene expression and complex traits and diseases. Our results highlight the important role of recent evolution in regulatory sequence elements differentiating primates, including humans, from other placental mammals., (© 2023. The Author(s).)

The rich diversity of morphology and behavior displayed across primate species provides an informative context in which to study the impact of genomic diversity on fundamental biological processes. Analysis of that diversity provides insight into long-standing questions in evolutionary and conservation biology and is urgent given severe threats these species are facing. Here, we present high-coverage whole-genome data from 233 primate species representing 86% of genera and all 16 families. This dataset was used, together with fossil calibration, to create a nuclear DNA phylogeny and to reassess evolutionary divergence times among primate clades. We found within-species genetic diversity across families and geographic regions to be associated with climate and sociality, but not with extinction risk. Furthermore, mutation rates differ across species, potentially influenced by effective population sizes. Lastly, we identified extensive recurrence of missense mutations previously thought to be human specific. This study will open a wide range of research avenues for future primate genomic research.

Baboons (genus Papio ) are a morphologically and behaviorally diverse clade of catarrhine monkeys that have experienced hybridization between phenotypically and genetically distinct phylogenetic species. We used high-coverage whole-genome sequences from 225 wild baboons representing 19 geographic localities to investigate population genomics and interspecies gene flow. Our analyses provide an expanded picture of evolutionary reticulation among species and reveal patterns of population structure within and among species, including differential admixture among conspecific populations. We describe the first example of a baboon population with a genetic composition that is derived from three distinct lineages. The results reveal processes, both ancient and recent, that produced the observed mismatch between phylogenetic relationships based on matrilineal, patrilineal, and biparental inheritance. We also identified several candidate genes that may contribute to species-specific phenotypes.

Personalized genome sequencing has revealed millions of genetic differences between individuals, but our understanding of their clinical relevance remains largely incomplete. To systematically decipher the effects of human genetic variants, we obtained whole-genome sequencing data for 809 individuals from 233 primate species and identified 4.3 million common protein-altering variants with orthologs in humans. We show that these variants can be inferred to have nondeleterious effects in humans based on their presence at high allele frequencies in other primate populations. We use this resource to classify 6% of all possible human protein-altering variants as likely benign and impute the pathogenicity of the remaining 94% of variants with deep learning, achieving state-of-the-art accuracy for diagnosing pathogenic variants in patients with genetic diseases.

High-risk childhood leukemia has a poor prognosis because of treatment failure and toxic side effects of therapy. Drug encapsulation into liposomal nanocarriers has shown clinical success at improving biodistribution and tolerability of chemotherapy. However, enhancements in drug efficacy have been limited because of a lack of selectivity of the liposomal formulations for the cancer cells. Here, we report on the generation of bispecific antibodies (BsAbs) with dual binding to a leukemic cell receptor, such as CD19, CD20, CD22, or CD38, and methoxy polyethylene glycol (PEG) for the targeted delivery of PEGylated liposomal drugs to leukemia cells. This liposome targeting system follows a "mix-and-match" principle where BsAbs were selected on the specific receptors expressed on leukemia cells. BsAbs improved the targeting and cytotoxic activity of a clinically approved and low-toxic PEGylated liposomal formulation of doxorubicin (Caelyx) toward leukemia cell lines and patient-derived samples that are immunophenotypically heterogeneous and representative of high-risk subtypes of childhood leukemia. BsAb-assisted improvements in leukemia cell targeting and cytotoxic potency of Caelyx correlated with receptor expression and were minimally detrimental in vitro and in vivo toward expansion and functionality of normal peripheral blood mononuclear cells and hematopoietic progenitors. Targeted delivery of Caelyx using BsAbs further enhanced leukemia suppression while reducing drug accumulation in the heart and kidneys and extended overall survival in patient-derived xenograft models of high-risk childhood leukemia. Our methodology using BsAbs therefore represents an attractive targeting platform to potentiate the therapeutic efficacy and safety of liposomal drugs for improved treatment of high-risk leukemia.

Myelodysplastic neoplasms (MDSs) and chronic myelomonocytic leukemia (CMML) are clonal disorders driven by progressively acquired somatic mutations in hematopoietic stem cells (HSCs). Hypomethylating agents (HMAs) can modify the clinical course of MDS and CMML. Clinical improvement does not require eradication of mutated cells and may be related to improved differentiation capacity of mutated HSCs. However, in patients with established disease it is unclear whether (1) HSCs with multiple mutations progress through differentiation with comparable frequency to their less mutated counterparts or (2) improvements in peripheral blood counts following HMA therapy are driven by residual wild-type HSCs or by clones with particular combinations of mutations. To address these questions, the somatic mutations of individual stem cells, progenitors (common myeloid progenitors, granulocyte monocyte progenitors, and megakaryocyte erythroid progenitors), and matched circulating hematopoietic cells (monocytes, neutrophils, and naïve B cells) in MDS and CMML were characterized via high-throughput single-cell genotyping, followed by bulk analysis in immature and mature cells before and after AZA treatment. The mutational burden was similar throughout differentiation, with even the most mutated stem and progenitor clones maintaining their capacity to differentiate to mature cell types in vivo. Increased contributions from productive mutant progenitors appear to underlie improved hematopoiesis in MDS following HMA therapy., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Mammal declines across northern Australia are one of the major biodiversity loss events occurring globally. There has been no regional assessment of the implications of these species declines for genomic diversity. To address this, we conducted a species-wide assessment of genomic diversity in the northern quoll (Dasyurus hallucatus), an Endangered marsupial carnivore. We used next generation sequencing methods to genotype 10,191 single nucleotide polymorphisms (SNPs) in 352 individuals from across a 3220-km length of the continent, investigating patterns of population genomic structure and diversity, and identifying loci showing signals of putative selection. We found strong heterogeneity in the distribution of genomic diversity across the continent, characterized by (i) biogeographical barriers driving hierarchical population structure through long-term isolation, and (ii) severe reductions in diversity resulting from population declines, exacerbated by the spread of introduced toxic cane toads (Rhinella marina). These results warn of a large ongoing loss of genomic diversity and associated adaptive capacity as mammals decline across northern Australia. Encouragingly, populations of the northern quoll established on toad-free islands by translocations appear to have maintained most of the initial genomic diversity after 16 years. By mapping patterns of genomic diversity within and among populations, and investigating these patterns in the context of population declines, we can provide conservation managers with data critical to informed decision-making. This includes the identification of populations that are candidates for genetic management, the importance of remnant island and insurance/translocated populations for the conservation of genetic diversity, and the characterization of putative evolutionarily significant units., (© 2022 The Authors. Molecular Ecology published by John Wiley & Sons Ltd.)

(1) Background: MALDI imaging is a technique that still largely depends on time of flight (TOF)-based instrument such as the Bruker UltrafleXtreme. While capable of performing targeted MS/MS, these instruments are unable to perform fragmentation while imaging a tissue section necessitating the reliance of MS1 values for peptide level identifications. With this premise in mind, we have developed a hybrid bioinformatic/image-based method for the identification and validation of viral biomarkers. (2) Methods: Formalin-Fixed Paraffin-Embedded (FFPE) mouse samples were sectioned, mounted and prepared for mass spectrometry imaging using our well-established methods. Peptide identification was achieved by first extracting confident images corresponding to theoretical viral peptides. Next, those masses were used to perform a Peptide Mmass Fingerprint (PMF) searched against known viral FASTA sequences against a background mouse FASTA database. Finally, a correlational analysis was performed with imaging data to confirm pixel-by-pixel colocalization and intensity of viral peptides. (3) Results: 14 viral peptides were successfully identified with significant PMF Scores and a correlational result of >0.79 confirming the presence of the virus and distinguishing it from the background mouse proteins. (4) Conclusions: this novel approach leverages the power of mass spectrometry imaging and provides confident identifications for viral proteins without requiring MS/MS using simple MALDI Time Of Flight/Time Of Flight (TOF/TOF) instrumentation.

Both fire and predators have strong influences on the population dynamics and behaviour of animals, and the effects of predators may either be strengthened or weakened by fire. However, knowledge of how fire drives or mediates predator-prey interactions is fragmented and has not been synthesised. Here, we review and synthesise knowledge of how fire influences predator and prey behaviour and interactions. We develop a conceptual model based on predator-prey theory and empirical examples to address four key questions: (i) how and why do predators respond to fire; (ii) how and why does prey vulnerability change post-fire; (iii) what mechanisms do prey use to reduce predation risk post-fire; and (iv) what are the outcomes of predator-fire interactions for prey populations? We then discuss these findings in the context of wildlife conservation and ecosystem management before outlining priorities for future research. Fire-induced changes in vegetation structure, resource availability, and animal behaviour influence predator-prey encounter rates, the amount of time prey are vulnerable during an encounter, and the conditional probability of prey death given an encounter. How a predator responds to fire depends on fire characteristics (e.g. season, severity), their hunting behaviour (ambush or pursuit predator), movement behaviour, territoriality, and intra-guild dynamics. Prey species that rely on habitat structure for avoiding predation often experience increased predation rates and lower survival in recently burnt areas. By contrast, some prey species benefit from the opening up of habitat after fire because it makes it easier to detect predators and to modify their behaviour appropriately. Reduced prey body condition after fire can increase predation risk either through impaired ability to escape predators, or increased need to forage in risky areas due to being energetically stressed. To reduce risk of predation in the post-fire environment, prey may change their habitat use, increase sheltering behaviour, change their movement behaviour, or use camouflage through cryptic colouring and background matching. Field experiments and population viability modelling show instances where fire either amplifies or does not amplify the impacts of predators on prey populations, and vice versa. In some instances, intense and sustained post-fire predation may lead to local extinctions of prey populations. Human disruption of fire regimes is impacting faunal communities, with consequences for predator and prey behaviour and population dynamics. Key areas for future research include: capturing data continuously before, during and after fires; teasing out the relative importance of changes in visibility and shelter availability in different contexts; documenting changes in acoustic and olfactory cues for both predators and prey; addressing taxonomic and geographic biases in the literature; and predicting and testing how changes in fire-regime characteristics reshape predator-prey interactions. Understanding and managing the consequences for predator-prey communities will be critical for effective ecosystem management and species conservation in this era of global change., (© 2022 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Primates have adapted to numerous environments and lifestyles but very few species are native to high elevations. Here we investigated high-altitude adaptations in the gelada (Theropithecus gelada), a monkey endemic to the Ethiopian Plateau. We examined genome-wide variation in conjunction with measurements of haematological and morphological traits. Our new gelada reference genome is highly intact and assembled at chromosome-length levels. Unexpectedly, we identified a chromosomal polymorphism in geladas that could potentially contribute to reproductive barriers between populations. Compared with baboons at low altitude, we found that high-altitude geladas exhibit significantly expanded chest circumferences, potentially allowing for greater lung surface area for increased oxygen diffusion. We identified gelada-specific amino acid substitutions in the alpha-chain subunit of adult haemoglobin but found that gelada haemoglobin does not exhibit markedly altered oxygenation properties compared with lowland primates. We also found that geladas at high altitude do not exhibit elevated blood haemoglobin concentrations, in contrast to the normal acclimatization response to hypoxia in lowland primates. The absence of altitude-related polycythaemia suggests that geladas are able to sustain adequate tissue-oxygen delivery despite environmental hypoxia. Finally, we identified numerous genes and genomic regions exhibiting accelerated rates of evolution, as well as gene families exhibiting expansions in the gelada lineage, potentially reflecting altitude-related selection. Our findings lend insight into putative mechanisms of high-altitude adaptation while suggesting promising avenues for functional hypoxia research., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Earth's rapidly warming climate is propelling us towards an increasingly fire-prone future. Currently, knowledge of the extent and characteristics of animal mortality rates during fire remains rudimentary, hindering our ability to predict how animal populations may be impacted in the future. To address this knowledge gap, we conducted a global systematic review of the direct effects of fire on animal mortality rates, based on studies that unequivocally determined the fate of animals during fire. From 31 studies spanning 1984-2020, we extracted data on the direct impacts of fire on the mortality of 31 species from 23 families. From these studies, there were 43 instances where direct effects were measured by reporting animal survival from pre- to post-fire. Most studies were conducted in North America (52%) and Oceania (42%), focused largely on mammals (53%) and reptiles (30%), and reported mostly on animal survival in planned (82%) and/or low severity (70%) fires. We found no studies from Asia, Europe or South America. Although there were insufficient data to conduct a formal meta-analysis, we tested the effect of fire type, fire severity, fire regime, animal body mass, ecological attributes and class on survival. Only fire severity affected animal mortality, with a higher proportion of animals being killed by high than low severity fires. Recent catastrophic fires across the globe have drawn attention to the plight of animals exposed to wildfire. Yet, our systematic review suggests that a relatively low proportion of animals (mean predicted mortality [95% CI] = 3% [1%-9%]) are killed during fire. However, our review also underscores how little we currently know about the direct effects of fire on animal mortality, and highlights the critical need to understand the effects of high severity fire on animal populations., (© 2022 John Wiley & Sons Ltd.)

Urban ecosystems and remnant habitat 'islands' therein, provide important strongholds for many wildlife species including those of conservation significance. However, the persistence of these habitats can be undermined if their structure and function are too severely disrupted. Urban wetlands, specifically, are usually degraded by a monoculture of invasive vegetation, disrupted hydrology, and chronic-contamination from a suite of anthropogenic pollutants. Top predators-as bioindicators-can be used to assess and monitor the health of these ecosystems. We measured eight health parameters (e.g., parasites, wounds and scars, tail loss and body condition) in a wetland top predator, the western tiger snake, Notechis scutatus occidentalis. For three years, snakes were sampled across four wetlands along an urban gradient. For each site, we used GIS software to measure the area of different landscapes and calculate an urbanisation-landscape score. Previously published research on snake contamination informed our calculations of a metal-pollution index for each site. We used generalised linear mixed models to assess the relationship between all health parameters and site variables. We found the metal-pollution index to have the most significant association with poor body condition. Although parasitism, tail loss and wounds differed among sites, none of these parameters influenced body condition. Additionally, the suite of health parameters suggested differing health status among sites; however, our measure of contemporary landscape urbanisation was never a significant predictor variable. Our results suggest that the health of wetland predators surrounding a rapidly growing city may be offset by higher levels of environmental pollution., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chronic kidney disease (CKD) is a common cause of morbidity and mortality in domestic cats, but the cause is still largely elusive. While some viruses have been associated with this disease, none have been definitively implicated as causative. Recently, Rodent chaphamaparvovirus 1 was recognized as the cause of murine inclusion body nephropathy, a disease reported for over 40 years in laboratory mice. A novel virus belonging to the same genus, Carnivore chaphamaparvovirus 2, was recently identified in the feces of cats with diarrhea. The goal of this study was to investigate the possible role of chaphamaparvoviruses including members of Rodent chaphamaparvovirus 1 and Carnivore chaphamaparvovirus 2 in the development of feline CKD. The presence of these viruses was retrospectively investigated in formalin-fixed paraffin-embedded feline kidney samples using polymerase chain reaction, in situ hybridization, and immunohistochemistry. Cats were divided into 3 groups: normal ( N = 24), CKD ( N = 26), and immunocompromised ( N = 25). None of the kidney tissues from any of the 75 cats revealed the presence of chaphamaparvovirus DNA, RNA, or antigen. We conclude that viruses belonging to the chaphamaparvovirus genus are unlikely to contribute to the occurrence of feline CKD.

Planet Earth is entering the age of megafire, pushing ecosystems to their limits and beyond. While fire causes mortality of animals across vast portions of the globe, scientists are only beginning to consider fire as an evolutionary force in animal ecology. Here, we generate a series of hypotheses regarding animal responses to fire by adopting insights from the predator-prey literature. Fire is a lethal threat; thus, there is likely strong selection for animals to recognize the olfactory, auditory, and visual cues of fire, and deploy fire avoidance behaviours that maximize survival probability. If fire defences are costly, it follows that intraspecific variation in fire avoidance behaviours should correspond with variation in fire behaviour and regimes. Species and populations inhabiting ecosystems that rarely experience fire may lack these traits, placing 'fire naive' populations and species at enhanced extinction risk as the distribution of fire extends into new ecosystem types. We outline a research agenda to understand behavioural responses to fire and to identify conservation interventions that could be used to overcome fire naivety., (© 2021 John Wiley & Sons Ltd.)

Cultural adaptation is one means by which conservationists may help populations adapt to threats. A learned behavior may protect an individual from a threat, and the behavior can be transmitted horizontally (within generations) and vertically (between generations), rapidly conferring population-level protection. Although possible in theory, it remains unclear whether such manipulations work in a conservation setting; what conditions are required for them to work; and how they might affect the evolutionary process. We examined models in which a population can adapt through both genetic and cultural mechanisms. Our work was motivated by the invasion of highly toxic cane toads (Rhinella marina) across northern Australia and the resultant declines of endangered northern quolls (Dasyurus hallucatus), which attack and are fatally poisoned by the toxic toads. We examined whether a novel management strategy in which wild quolls are trained to avoid toads can reduce extinction probability. We used a simulation model tailored to quoll life history. Within simulations, individuals were trained and a continuous evolving trait determined innate tendency to attack toads. We applied this model in a population viability setting. The strategy reduced extinction probability only when heritability of innate aversion was low (<20%) and when trained mothers trained >70% of their young to avoid toads. When these conditions were met, genetic adaptation was slower, but rapid cultural adaptation kept the population extant while genetic adaptation was completed. To gain insight into the evolutionary dynamics (in which we saw a transitory peak in cultural adaptation over time), we also developed a simple analytical model of evolutionary dynamics. This model showed that the strength of natural selection declined as the cultural transmission rate increased and that adaptation proceeded only when the rate of cultural transmission was below a critical value determined by the relative levels of protection conferred by genetic versus cultural mechanisms. Together, our models showed that cultural adaptation can play a powerful role in preventing extinction, but that rates of cultural transmission need to be high for this to occur., (© 2021 Society for Conservation Biology.)

The arrival of novel predators can trigger trophic cascades driven by shifts in prey numbers. Predators also elicit behavioral change in prey populations, via phenotypic plasticity and/or rapid evolution, and such changes may also contribute to trophic cascades. Here, we document rapid demographic and behavioral changes in populations of a prey species (grassland melomys Melomys burtoni, a granivorous rodent) following the introduction of a novel marsupial predator (northern quoll Dasyurus hallucatus). Within months of quolls appearing, populations of melomys exhibited reduced survival and population declines relative to control populations. Quoll-invaded populations were also significantly shyer than nearby, quoll-free populations of conspecifics. This rapid but generalized response to a novel threat was replaced over the following 2 yr with more threat-specific antipredator behaviors (i.e., predator-scent aversion). Predator-exposed populations, however, remained more neophobic than predator-free populations throughout the study. These behavioral responses manifested rapidly in changed rates of seed predation by melomys across treatments. Quoll-invaded melomys populations exhibited lower per-capita seed take rates, and rapidly developed an avoidance of seeds associated with quoll scent, with discrimination playing out over a spatial scale of tens of meters. Presumably the significant and novel predation pressure induced by quolls drove melomys populations to fine-tune behavioral responses to be more predator specific through time. These behavioral shifts could reflect individual plasticity (phenotypic flexibility) in behavior or may be adaptive shifts from natural selection imposed by quoll predation. Our study provides a rare insight into the rapid ecological and behavioral shifts enacted by prey to mitigate the impacts of a novel predator and shows that trophic cascades can be strongly influenced by behavioral as well as numerical responses., (© 2021 by the Ecological Society of America.)