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1. Intergenomic signatures of coevolution between Tasmanian devils and an infectious cancer

   https://doi.org/10.1073/pnas.2307780121  

   Gallinson, Dylan G.; Kozakiewicz, Christopher P.; Rautsaw, Rhett M.; Beer, Marc A.; Ruiz-Aravena, Manuel; Comte, Sebastien; Hamilton, David G.; Kerlin, Douglas H.; McCallum, Hamish I.; Hamede, Rodrigo; et al (March 2024, Proceedings of the National Academy of Sciences)

   Coevolution is common and frequently governs host–pathogen interaction outcomes. Phenotypes underlying these interactions often manifest as the combined products of the genomes of interacting species, yet traditional quantitative trait mapping approaches ignore these intergenomic interactions. Devil facial tumor disease (DFTD), an infectious cancer afflicting Tasmanian devils (Sarcophilus harrisii), has decimated devil populations due to universal host susceptibility and a fatality rate approaching 100%. Here, we used a recently developed joint genome-wide association study (i.e., co-GWAS) approach, 15 y of mark-recapture data, and 960 genomes to identify intergenomic signatures of coevolution between devils and DFTD. Using a traditional GWA approach, we found that both devil and DFTD genomes explained a substantial proportion of variance in how quickly susceptible devils became infected, although genomic architectures differed across devils and DFTD; the devil genome had fewer loci of large effect whereas the DFTD genome had a more polygenic architecture. Using a co-GWA approach, devil–DFTD intergenomic interactions explained ~3× more variation in how quickly susceptible devils became infected than either genome alone, and the top genotype-by-genotype interactions were significantly enriched for cancer genes and signatures of selection. A devil regulatory mutation was associated with differential expression of a candidate cancer gene and showed putative allele matching effects with two DFTD coding sequence variants. Our results highlight the need to account for intergenomic interactions when investigating host–pathogen (co)evolution and emphasize the importance of such interactions when considering devil management strategies. 

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2. Adaptive potential in the face of a transmissible cancer in Tasmanian devils

   https://doi.org/10.1111/mec.17531  

   Strickland, Kasha; Jones, Menna E; Storfer, Andrew; Hamede, Rodrigo K; Hohenlohe, Paul A; Margres, Mark J; McCallum, Hamish I; Comte, Sebastien; Lachish, Shelly; Kruuk, Loeske_E B (November 2024, Molecular Ecology)

   Abstract Emerging infectious diseases (EIDs) not only cause catastrophic declines in wildlife populations but also generate selective pressures that may result in rapid evolutionary responses. One such EID is devil facial tumour disease (DFTD) in the Tasmanian devil. DFTD is almost always fatal and has reduced the average lifespan of individuals by around 2 years, likely causing strong selection for traits that reduce susceptibility to the disease, but population decline has also left Tasmanian devils vulnerable to inbreeding depression. We analysed 22 years of data from an ongoing study of a population of Tasmanian devils on Freycinet Peninsula, Tasmania, to (1) identify whether DFTD may be causing selection on body size, by estimating phenotypic and genetic correlations between DFTD and size traits, (2) estimate the additive genetic variance of susceptibility to DFTD, and (3) investigate whether size traits or susceptibility to DFTD were under inbreeding depression. We found a positive phenotypic relationship between head width and susceptibility to DFTD, but this was not underpinned by a genetic correlation. Conversely, we found a negative phenotypic relationship between body weight and susceptibility to DFTD, and there was evidence for a negative genetic correlation between susceptibility to DFTD and body weight. There was additive genetic variance in susceptibility to DFTD, head width and body weight, but there was no evidence for inbreeding depression in any of these traits. These results suggest that Tasmanian devils have the potential to respond adaptively to DFTD, although the realised evolutionary response will critically further depend on the evolution of DFTD itself. 

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3. A transmissible cancer shifts from emergence to endemism in Tasmanian devils

   https://doi.org/10.1126/science.abb9772  

   Patton, Austin H.; Lawrance, Matthew F.; Margres, Mark J.; Kozakiewicz, Christopher P.; Hamede, Rodrigo; Ruiz-Aravena, Manuel; Hamilton, David G.; Comte, Sebastien; Ricci, Lauren E.; Taylor, Robyn L.; et al (December 2020, Science)

   Emerging infectious diseases pose one of the greatest threats to human health and biodiversity. Phylodynamics is often used to infer epidemiological parameters essential for guiding intervention strategies for human viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2). Here, we applied phylodynamics to elucidate the epidemiological dynamics of Tasmanian devil facial tumor disease (DFTD), a fatal, transmissible cancer with a genome thousands of times larger than that of any virus. Despite prior predictions of devil extinction, transmission rates have declined precipitously from ~3.5 secondary infections per infected individual to ~1 at present. Thus, DFTD appears to be transitioning from emergence to endemism, lending hope for the continued survival of the endangered Tasmanian devil. More generally, our study demonstrates a new phylodynamic analytical framework that can be applied to virtually any pathogen. 

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4. Adaptation and gene flow are insufficient to rescue a montane plant under climate change

   https://doi.org/10.1126/science.adr1010  

   Anderson, Jill T; DeMarche, Megan L; Denney, Derek A; Breckheimer, Ian; Santangelo, James; Wadgymar, Susana M (May 2025, Science)

   Climate change increasingly drives local population dynamics, shifts geographic distributions, and threatens persistence. Gene flow and rapid adaptation could rescue declining populations yet are seldom integrated into forecasts. We modeled eco-evolutionary dynamics under preindustrial, contemporary, and projected climates using up to 9 years of fitness data from 102,272 transplants (115 source populations) ofBoechera strictain five common gardens. Climate change endangers locally adapted populations and reduces genotypic variation in long-term population growth rate, suggesting limited adaptive potential. Upslope migration could stabilize high-elevation populations and preserve low-elevation ecotypes, but unassisted gene flow modeled with genomic data is too spatially restricted. Species distribution models failed to capture current dynamics and likely overestimate persistence under intermediate emissions scenarios, highlighting the importance of modeling evolutionary processes. 

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5. Spatial variation in gene expression of Tasmanian devil facial tumors despite minimal host transcriptomic response to infection

   https://doi.org/10.1186/s12864-021-07994-4  

   Kozakiewicz, Christopher P.; Fraik, Alexandra K.; Patton, Austin H.; Ruiz-Aravena, Manuel; Hamilton, David G.; Hamede, Rodrigo; McCallum, Hamish; Hohenlohe, Paul A.; Margres, Mark J.; Jones, Menna E.; et al (December 2021, BMC Genomics)

   Abstract Background Transmissible cancers lie at the intersection of oncology and infectious disease, two traditionally divergent fields for which gene expression studies are particularly useful for identifying the molecular basis of phenotypic variation. In oncology, transcriptomics studies, which characterize the expression of thousands of genes, have identified processes leading to heterogeneity in cancer phenotypes and individual prognoses. More generally, transcriptomics studies of infectious diseases characterize interactions between host, pathogen, and environment to better predict population-level outcomes. Tasmanian devils have been impacted dramatically by a transmissible cancer (devil facial tumor disease; DFTD) that has led to widespread population declines. Despite initial predictions of extinction, populations have persisted at low levels, due in part to heterogeneity in host responses, particularly between sexes. However, the processes underlying this variation remain unknown. Results We sequenced transcriptomes from healthy and DFTD-infected devils, as well as DFTD tumors, to characterize host responses to DFTD infection, identify differing host-tumor molecular interactions between sexes, and investigate the extent to which tumor gene expression varies among host populations. We found minimal variation in gene expression of devil lip tissues, either with respect to DFTD infection status or sex. However, 4088 genes were differentially expressed in tumors among our sampling localities. Pathways that were up- or downregulated in DFTD tumors relative to normal tissues exhibited the same patterns of expression with greater intensity in tumors from localities that experienced DFTD for longer. No mRNA sequence variants were associated with expression variation. Conclusions Expression variation among localities may reflect morphological differences in tumors that alter ratios of normal-to-tumor cells within biopsies. Phenotypic variation in tumors may arise from environmental variation or differences in host immune response that were undetectable in lip biopsies, potentially reflecting variation in host-tumor coevolutionary relationships among sites that differ in the time since DFTD arrival. 

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