Although cancer rarely acts as an infectious disease, a recently emerged transmissible cancer in Tasmanian devils (Sarcophilus harrisii) is virtually 100% fatal. Devil facial tumour disease (DFTD) has swept across nearly the entire species' range, resulting in localized declines exceeding 90% and an overall species decline of more than 80% in less than 20 years. Despite epidemiological models that predict extinction, populations in long-diseased sites persist. Here we report rare genomic evidence of a rapid, parallel evolutionary response to strong selection imposed by a wildlife disease. We identify two genomic regions that contain genes related to immune function or cancer risk in humans that exhibit concordant signatures of selection across three populations. DFTD spreads between hosts by suppressing and evading the immune system, and our results suggest that hosts are evolving immune-modulated resistance that could aid in species persistence in the face of this devastating disease.

Identifying the genetic architecture of complex phenotypes is a central goal of modern biology, particularly for disease-related traits. Genome-wide association methods are a classical approach for identifying the genomic basis of variation in disease phenotypes, but such analyses are particularly challenging in natural populations due to sample size difficulties. Extensive mark-recapture data, strong linkage disequilibrium and a lethal transmissible cancer make the Tasmanian devil (Sarcophilus harrisii) an ideal model for such an association study. We used a RAD-capture approach to genotype 624 devils at ~16,000 loci and then used association analyses to assess the heritability of three cancer-related phenotypes: infection case-control (where cases were infected devils and controls were devils that were never infected), age of first infection and survival following infection. The SNP array explained much of the phenotypic variance for female survival (>80%) and female case-control (>61%). We found that a few large-effect SNPs explained much of the variance for female survival (~5 SNPs explained >61% of the total variance), whereas more SNPs (~56) of smaller effect explained less of the variance for female case-control (~23% of the total variance). By contrast, these same SNPs did not account for a significant proportion of phenotypic variance in males, suggesting that the genetic bases of these traits and/or selection differ across sexes. Loci involved with cell adhesion and cell-cycle regulation underlay trait variation, suggesting that the devil immune system is rapidly evolving to recognize and potentially suppress cancer growth through these pathways. Overall, our study provided necessary data for genomics-based conservation and management in Tasmanian devils.

Tasmanian devils face a combination of threats to persistence, including Devil Facial Tumor Disease (DFTD), an epidemic transmissible cancer. We used RAD sequencing to investigate genome-wide patterns of genetic diversity and geographic population structure. Consistent with previous results, we found very low genetic diversity in the species as a whole, and we detected two broad genetic clusters occupying the northwestern portion of the range, and the central and eastern portions. However, these two groups overlap across a broad geographic area, and differentiation between them is modest (FST = 0.1081). Our results refine the geographic extent of the zone of mixed ancestry and substructure within it, potentially informing management of genetic variation that existed in pre-diseased populations of the species. DFTD has spread across both genetic clusters, but recent evidence points to a genomic response to selection imposed by DFTD. Any allelic variation for resistance to DFTD may be able to spread across the devil population under selection by DFTD, and/or be present as standing variation in both genetic regions.

Landscape genomics studies focus on identifying candidate genes under selection via spatial variation in abiotic environmental variables, but rarely by biotic factors (i.e., disease). The Tasmanian devil (Sarcophilus harrisii) is found only on the environmentally heterogeneous island of Tasmania and is threatened with extinction by a transmissible cancer, devil facial tumor disease (DFTD). Devils persist in regions of long‐term infection despite epidemiological model predictions of species’ extinction, suggesting possible adaptation to DFTD. Here, we test the extent to which spatial variation and genetic diversity are associated with the abiotic environment (i.e., climatic variables, elevation, vegetation cover) and/or DFTD. We employ genetic‐environment association analyses using 6886 SNPs from 3287 individuals sampled pre‐ and post‐disease arrival across the devil's geographic range. Pre‐disease, we find significant correlations of allele frequencies with environmental variables, including 365 unique loci linked to 71 genes, suggesting local adaptation to abiotic environment. The majority of candidate loci detected pre‐DFTD are not detected post‐DFTD arrival. Several post‐DFTD candidate loci are associated with disease prevalence and were in linkage disequilibrium with genes involved in tumor suppression and immune response. Loss of apparent signal of abiotic local adaptation post‐disease suggests swamping by strong selection resulting from the rapid onset of DFTD.

This finding is consistent with a greater propensity for long-distance dispersal for species of open habitats and proxy evidence that expansive areas of dry vegetation occurred during times of exposure of Bass Strait during glacials. Overall, this study provides novel genetic evidence that habitat type and its interaction with dispersal traits are major influences on dispersal of plants.