Disease swamps molecular signatures of genetic‐environmental associations to abiotic factors in Tasmanian devil ( Sarcophilus harrisii ) populations

Abstract

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.

Contemporary and historical selection in Tasmanian devils (Sarcophilus harrisii) support novel, polygenic response to transmissible cancer

“…Across six study sites that span the geographic range of Tasmanian devils, and genomic samples of over 2500 devils collected over 15 years, we found widespread signatures of rapid evolution in populations impacted by DFTD. Despite concerns that devils may not harbour sufficient genetic diversity to sufficiently respond to DFTD, we identified 186 candidate genes (Supplemental Table S4) with robust signatures of positive selection, reaffirming the adaptive potential of wild devils described in a growing body of work (2,47,48,70). Our targeted RADcapture sampling approach allowed us to sequence many more individual devils than previous studies and examine specific loci and regions of interest.…”

“…In the top 1% of DCMS scores, we identified 144 candidate SNPs for contemporary selection by DFTD; of these, 79 had annotated genes (186 total) within 100 kb (Figure 2; Supplemental Table S4). In our comparison of previously identified candidate genes in devils (47,48,50,63), we found many overlapping candidates (See Discussion), but only significant enrichment among our contemporary candidates for those associated with disease-related phenotypes (50), with the largest odds ratio for genes associated with phenotypes in females (14 genes, p-value=5.1e-08, Odds ratio=7.1). Gene ontology enrichment analysis found middle ear morphogenesis (GO:0042474) significantly enriched among contemporary candidate SNPs (FDR < 0.05).…”

“…To identify key mechanisms of adaptation among candidate genes, we used gene ontology (GO) term enrichment analysis using the SNP2GO package (61) and the PANTHER web-interface (62). We capitalized on the wealth of ongoing research in devils and DFTD by comparing our contemporary and historical candidates to those previously identified using different datasets and analytical approaches (2,47,48,50,63). We then tested for overrepresentation of contemporary and historical candidates in gene sets of the molecular signatures database (MsigDB) (64).…”

“…A high-quality reference genome for the devil yields deep evolutionary history insight and fine-scale mapping for functional inference of individual genotypes (27,32). Population genomic studies have already shown that devils are rapidly evolving in response to DFTD (2,47,48). From these data, a RAD-capture (Rapture; 49) panel has been developed to target 16,000 putative candidates and demographically-informative loci, facilitating the collection of data across hundreds of individuals in a single lane of sequencing.…”

Comparative landscape genetics reveals differential effects of environment on host and pathogen genetic structure in Tasmanian devils (Sarcophilus harrisii) and their transmissible tumour

“…Previous work indicates up to six genetic populations island-wide, including a clear distinction between individuals sampled from northwestern Tasmania and those from elsewhere on the island (Brüniche-Olsen, Jones, Austin, Burridge, & Holland, 2014;Fraik et al, 2020;Hendricks et al, 2017;Miller et al, 2011;Storfer et al, 2017). The cause of this east-to-west spatial genetic heterogeneity remains unclear, with previous landscape genetics work implementing least-cost path modelling and microsatellite loci unable to identify any landscape factors driving this variation (Storfer et al, 2017).…”