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

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.

Divergent hepaciviruses, delta-like viruses, and a chu-like virus in Australian marsupial carnivores (dasyurids)

“…We identified three species of novel RNA viruses in this study: two hepaciviruses (positive-sense RNA, family Flaviviridae), one in antechinus and one in a numbat, and a chu-like virus (negative-sense RNA virus, order Jingchuvirales) here named Tasmanian devil chu-like virus. The chu-like virus, which has an unsegmented, non-circular genome, was identified in a DFTD cell line that was cultured from primary tissue ( Kozakiewicz et al. 2021 ).…”

Transcriptomics of mussel transmissible cancer MtrBTN2 suggests accumulation of multiple cancerous traits and oncogenic pathways shared among bilaterians

“…As MtrBTN2 ploidy appears highly abnormal (varying between 8N to 18N, (18)), further investigations will be needed to determine whether the dysregulation of these DNA repair pathways favors recombination between homologous chromosomes and chromosomal abnormalities accumulation, or whether these pathways are activated in order to limit DNA damages. Interestingly, up-regulation of double-stranded DNA break repair via HR pathway was also found in DFTD (78).…”

“…Interestingly, up-regulation of double-stranded DNA break repair via HR pathway was also found in DFTD (78).…”

Complex associations between cancer progression and immune gene expression reveals early influence of transmissible cancer on Tasmanian devils

“…Expression of key adaptive immune genes decreased, and expression of some innate immune genes increased ( 21 ), whilst the T-cell repertoire constricted markedly ( 22 ). In contrast, a study using full transcriptomics showed little gene expression difference between infected and healthy animals ( 20 ). Our approach used both cross-sectional and longitudinal datasets, with a focus on DFTD infection, to allow insight into how individuals change their immune gene expression over the course of their life, particularly when confronted with DFTD infection.…”

“…Tasmanian devil responses to DFTD infection are complex, with no differences between the transcriptomes of healthy and DFTD infected animals detected in lip tissue ( 20 ). However, more targeted analysis from blood has shown shifts in immune gene expression with DFTD infection ( 21 ).…”