Kozakiewicz, CP and Fraik, AK and Patton, AH and Ruiz Aravena, M and Hamilton, DG and Hamede, R and McCallum, H and Hohenlohe, PA and Margres, MJ and Jones, ME and Storfer, A, Spatial variation in gene expression of Tasmanian devil facial tumors despite minimal host transcriptomic response to infection, BMC Genomics, 22 Article 698. ISSN 1471-2164 (2021) [Refereed Article]
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.
|Item Type:||Refereed Article|
|Keywords:||Tasmanian devil facial tumour disease, rapid evolution, transmissible cancer, host-pathogen coevolution, wildlife disease, population transcriptomics|
|Research Division:||Biological Sciences|
|Research Group:||Evolutionary biology|
|Research Field:||Biological adaptation|
|Objective Division:||Environmental Management|
|Objective Group:||Terrestrial systems and management|
|Objective Field:||Control of pests, diseases and exotic species in terrestrial environments|
|UTAS Author:||Ruiz Aravena, M (Mr Manuel Ruiz Aravena)|
|UTAS Author:||Hamilton, DG (Mr David Hamilton)|
|UTAS Author:||Hamede, R (Dr Rodrigo Hamede Ross)|
|UTAS Author:||Jones, ME (Professor Menna Jones)|
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