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


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Kozakiewicz, CP, Fraik, AK, Patton, AH, Ruiz Aravena, M, Hamilton, DG, Hamede, R ORCID: 0000-0003-1526-225X, McCallum, H, Hohenlohe, PA, Margres, MJ, Jones, ME ORCID: 0000-0001-7558-9022 and Storfer, A 2021 , 'Spatial variation in gene expression of Tasmanian devil facial tumors despite minimal host transcriptomic response to infection' , BMC Genomics, vol. 22 , pp. 1-19 , doi: 10.1186/s12864-021-07994-4.

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Background: Transmissible cancers lie at the intersection of oncology and infectious disease, two traditionallydivergent fields for which gene expression studies are particularly useful for identifying the molecular basis ofphenotypic 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 tobetter predict population-level outcomes. Tasmanian devils have been impacted dramatically by a transmissiblecancer (devil facial tumor disease; DFTD) that has led to widespread population declines. Despite initial predictionsof extinction, populations have persisted at low levels, due in part to heterogeneity in host responses, particularlybetween sexes. However, the processes underlying this variation remain unknown.Results: We sequenced transcriptomes from healthy and DFTD-infected devils, as well as DFTD tumors, tocharacterize 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 minimalvariation in gene expression of devil lip tissues, either with respect to DFTD infection status or sex. However, 4088genes were differentially expressed in tumors among our sampling localities. Pathways that were up- ordownregulated in DFTD tumors relative to normal tissues exhibited the same patterns of expression with greaterintensity in tumors from localities that experienced DFTD for longer. No mRNA sequence variants were associatedwith expression variation.Conclusions: Expression variation among localities may reflect morphological differences in tumors that alter ratiosof normal-to-tumor cells within biopsies. Phenotypic variation in tumors may arise from environmental variation ordifferences in host immune response that were undetectable in lip biopsies, potentially reflecting variation in host-tumorcoevolutionary relationships among sites that differ in the time since DFTD arrival.

Item Type: Article
Authors/Creators: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
Keywords: Tasmanian devil facial tumour disease, rapid evolution, transmissible cancer, host-pathogen coevolution, wildlife disease, population transcriptomics
Journal or Publication Title: BMC Genomics
Publisher: Biomed Central Ltd
ISSN: 1471-2164
DOI / ID Number: 10.1186/s12864-021-07994-4
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© The Author(s) 2021. Open Access This article is licensed under a Creative CommonsAttribution 4.0 International (CC BY 4.0) License, ( which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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