Disruption of metapopulation structure reduces Tasmanian devil facial tumour disease spread at the expense of abundance and genetic diversity

Metapopulation structure plays a fundamental role in the persistence of wildlife populations. It can also drive the spread of infectious diseases and transmissible cancers such as the Tasmanian devil facial tumour disease (DFTD). While disrupting this structure can reduce disease spread, it can also impair host resilience by disrupting gene flow and colonisation dynamics. Using an individual-based metapopulation model we investigated the synergistic effects of host dispersal, disease transmission rate and inter-individual contact distance for transmission, on the spread and persistence of DFTD from local to regional scales. Disease spread, and the ensuing population declines, are synergistically determined by individuals’ dispersal, disease transmission rate and within-population mixing. Transmission rates can be magnified by high dispersal and inter-individual transmission distance. The isolation of local populations effectively reduced metapopulation-level disease prevalence but caused severe declines in metapopulation size and genetic diversity. The relative position of managed (i.e., isolated) local populations had a significant effect on disease prevalence, highlighting the importance of considering metapopulation structure when implementing metapopulation-scale disease control measures. Our findings suggest that population isolation is not an ideal management method for preventing disease spread in species inhabiting already fragmented landscapes, where genetic diversity and extinction risk are already a concern

In vitro competition between two transmissible cancers and potential implications for their host, the Tasmanian devil

Since the emergence of a transmissible cancer, devil facial tumour disease (DFT1), in the 1980s, wild Tasmanian devil populations have been in decline. In 2016, a second, independently evolved transmissible cancer (DFT2) was discovered raising concerns for survival of the host species. Here, we applied experimental and modelling frameworks to examine competition dynamics between the two transmissible cancers in vitro. Using representative cell lines for DFT1 and DFT2, we have found that in monoculture, DFT2 grows twice as fast as DFT1 but reaches lower maximum cell densities. Using co-cultures, we demonstrate that DFT2 outcompetes DFT1: the number of DFT1 cells decreasing over time, never reaching exponential growth. This phenomenon could not be replicated when cells were grown separated by a semi-permeable membrane, consistent with exertion of mechanical stress on DFT1 cells by DFT2. A logistic model and a Lotka-Volterra competition model were used to interrogate monoculture and co-culture growth curves, respectively, suggesting DFT2 is a better competitor than DFT1, but also showing that competition outcomes might depend on the initial number of cells, at least in the laboratory. We provide theories how the in vitro results could be translated to observations in the wild and propose that these results may indicate that although DFT2 is currently in a smaller geographic area than DFT1, it could have the potential to outcompete DFT1. Furthermore, we provide a framework for improving the parameterization of epidemiological models applied to these cancer lineages, which will inform future disease management.</p

The ecology and evolution of wildlife cancers: Applications for management and conservation

Evolutionary Applications published by John Wiley &amp; Sons Ltd Ecological and evolutionary concepts have been widely adopted to understand host&ndash;pathogen dynamics, and more recently, integrated into wildlife disease management. Cancer is a ubiquitous disease that affects most metazoan species; however, the role of oncogenic phenomena in eco-evolutionary processes and its implications for wildlife management and conservation remains undeveloped. Despite the pervasive nature of cancer across taxa, our ability to detect its occurrence, progression and prevalence in wildlife populations is constrained due to logistic and diagnostic limitations, which suggests that most cancers in the wild are unreported and understudied. Nevertheless, an increasing number of virus-associated and directly transmissible cancers in terrestrial and aquatic environments have been detected. Furthermore, anthropogenic activities and sudden environmental changes are increasingly associated with cancer incidence in wildlife. This highlights the need to upscale surveillance efforts, collection of critical data and developing novel approaches for studying the emergence and evolution of cancers in the wild. Here, we discuss the relevance of malignant cells as important agents of selection and offer a holistic framework to understand the interplay of ecological, epidemiological and evolutionary dynamics of cancer in wildlife. We use a directly transmissible cancer (devil facial tumour disease) as a model system to reveal the potential evolutionary dynamics and broader ecological effects of cancer epidemics in wildlife. We provide further examples of tumour&ndash;host interactions and trade-offs that may lead to changes in life histories, and epidemiological and population dynamics. Within this framework, we explore immunological strategies at the individual level as well as transgenerational adaptations at the population level. Then, we highlight the need to integrate multiple disciplines to undertake comparative cancer research at the human&ndash;domestic&ndash;wildlife interface and their environments. Finally, we suggest strategies for screening cancer incidence in wildlife and discuss how to integrate ecological and evolutionary concepts in the management of current and future cancer epizootics

Darwin, the devil, and the management of transmissible cancers

Modern conservation science frequently relies on genetic tools to manage imperiled populations threatened by processes such as habitat fragmentation and infectious diseases. Translocation of individuals to restore genetic diversity (genetic rescue) is increasingly used to manage vulnerable populations, but it can swamp local adaptations and lead to outbreeding depression. Thus, genetic management is context dependent and needs evaluation across multiple generations . Genomic studies can help evaluate the extent to which populations are locally adapted to assess the costs and benefits of translocations. Predicting the long‐term fitness effects of genetic interventions and their evolutionary consequences is a vital step in managing dwindling populations threatened by emerging infectious diseases

Transmissible cancer and the evolution of sex

The origin and subsequent maintenance of sex and recombination are among the most elusive and controversial problems in evolutionary biology. Here, we propose a novel hypothesis, suggesting that sexual reproduction not only evolved to reduce the negative effects of the accumulation of deleterious mutations and processes associated with pathogen and/or parasite resistance but also to prevent invasion by transmissible selfish neoplastic cheater cells, henceforth referred to as transmissible cancer cells. Sexual reproduction permits systematic change of the multicellular organism\u27s genotype and hence an enhanced detection of transmissible cancer cells by immune system. Given the omnipresence of oncogenic processes in multicellular organisms, together with the fact that transmissible cancer cells can have dramatic effects on their host fitness, our scenario suggests that the benefits of sex and concomitant recombination will be large and permanent, explaining why sexual reproduction is, despite its costs, the dominant mode of reproduction among eukaryotes

Global meta‐analysis of over 50 years of multidisciplinary and international collaborations on transmissible cancers

International audienceAlthough transmissible cancers have, so far, only been documented in three independent animal groups, they not only impact animals that have high economic, environmental and social significance, but they are also one of the most virulent parasitic life forms. Currently known transmissible cancers traverse terrestrial and marine environments, and are predicted to be more widely distributed across animal groups; thus, the implementation of effective collaborative scientific networks is important for combating existing and emerging forms. Here, we quantify how collaborative effort on the three known transmissible cancers has advanced through the formation of collaborative networks among institutions and disciplines. These three cancers occur in bivalves (invertebrates—disseminated neoplasia; DN), Tasmanian devils (vertebrate—marsupial; devil facial tumour disease; DFTD) and dogs (vertebrate—eutherian mammal; canine transmissible venereal tumour; CTVT). Research on CTVT and DN has been conducted since 1876 and 1969, respectively, whereas systematic research on DFTD only started in 2006. Yet, collaborative effort on all three diseases is global, encompassing six major Scopus subject areas. Collaborations steadily increased between 1963 and 2006 for CTVT and DN, with similar acceleration for all three cancers since 2006. Network analyses demonstrated that scientists are organizing themselves into efficient collaborative networks; however, these networks appear to be far stronger for DFTD and DN, possibly due to the recent detection of new strains adding impetus to research and associated publications (enhancing citation trajectories). In particular, global and multidisciplinary collaborations formed almost immediately after DFTD research was initiated, leading to similar research effort and relatively greater research outputs compared to the other two diseases. Therefore, in the event of outbreaks of new lineages of existing transmissible cancers, or the discovery of new transmissible cancers in the future, the rapid formation of international collaborations spanning relevant disciplines is vital for the efficient management of these diseases

Ecological and evolutionary consequences of anticancer adaptations

Cellular cheating leading to cancers exists in all branches of multicellular life, favoring the evolution of adaptations to avoid or suppress malignant progression, and/or to alleviate its fitness consequences. Ecologists have until recently largely neglected the importance of cancer cells for animal ecology, presumably because they did not consider either the potential ecological or evolutionary consequences of anticancer adaptations. Here, we review the diverse ways in which the evolution of anticancer adaptations has significantly constrained several aspects of the evolutionary ecology of multicellular organisms at the cell, individual, population, species, and ecosystem levels and suggest some avenues for future research

New Insights into the Role of MHC Diversity in Devil Facial Tumour Disease

Devil facial tumour disease (DFTD) is a fatal contagious cancer that has decimated Tasmanian devil populations. The tumour has spread without invoking immune responses, possibly due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. Animals from a region in north-western Tasmania have lower infection rates than those in the east of the state. This area is a genetic transition zone between sub-populations, with individuals from north-western Tasmania displaying greater diversity than eastern devils at MHC genes, primarily through MHC class I gene copy number variation. Here we test the hypothesis that animals that remain healthy and tumour free show predictable differences at MHC loci compared to animals that develop the disease

Is adaptive therapy natural?

Research suggests that progression-free survival can be prolonged by integrating evolutionary principles into clinical cancer treatment protocols. The goal is to prevent or slow the proliferation of resistant malignant cell populations. The logic behind this therapy relies on ecological and evolutionary processes. These same processes would be available to natural selection in decreasing the probability of an organism\u27s death due to cancer. We propose that organisms\u27 anticancer adaptions include not only ones for preventing cancer but also ones for directing and retarding the evolution of life-threatening cancer cells. We term this last strategy natural adaptive therapy (NAT). The body\u27s NAT might include a lower than otherwise possible immune response. A restrained immune response might forego maximum short-term kill rates. Restraint would forestall immune-resistant cancer cells and produce long-term durable control of the cancer population. Here, we define, develop, and explore the possibility of NAT. The discovery of NAT mechanisms could identify new strategies in tumor prevention and treatments. Furthermore, we discuss the potential risks of immunotherapies that force the immune system to ramp up the short-term kill rates of malignant cancer cells in a manner that undermines the body\u27s NAT and accelerates the evolution of immune resistance

Human habitat modification, not apex scavenger decline, drives isotopic niche variation in a carnivore community

Top carnivores can influence the structure of ecological communities, primarily through competition and predation; however, communities are also influenced by bottom-up forces such as anthropogenic habitat disturbance. Top carnivore declines will likely alter competitive dynamics within and amongst sympatric carnivore species. Increasing intraspecific competition is generally predicted to drive niche expansion and/or individual specialisation, while interspecific competition tends to constrain niches. Using stable isotope analysis of whiskers, we studied the effects of Tasmanian devil Sarcophilus harrisii declines upon the population- and individual-level isotopic niches of Tasmanian devils and sympatric spotted-tailed quolls Dasyurus maculatus subsp. maculatus. We investigated whether time since the onset of devil decline (a proxy for severity of decline) and landscape characteristics affected the isotopic niche breadth and overlap of devil and quoll populations. We quantified individual isotopic niche breadth for a subset of Tasmanian devils and spotted-tailed quolls and assessed whether between-site population niche variation was driven by individual-level specialisation. Tasmanian devils and spotted-tailed quolls demonstrated smaller population-level isotopic niche breadths with increasing human-modified habitat, while time since the onset of devil decline had no effect on population-level niche breadth or interspecific niche overlap. Individual isotopic niche breadths of Tasmanian devils and spotted-tailed quolls were narrower in human-modified landscapes, likely driving population isotopic niche contraction, however, the degree of individuals’ specialisation relative to one another remained constant. Our results suggest that across varied landscapes, mammalian carnivore niches can be more sensitive to the bottom-up forces of anthropogenic habitat disturbance than to the top-down effects of top carnivore decline