The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils.
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ABSTRACT:
SUBMITTER: Stammnitz MR
PROVIDER: S-EPMC5896245 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Tasmanian devils have spawned two transmissible cancer lineages, named devil facial tumor 1 (DFT1) and devil facial tumor 2 (DFT2). We investigated the genetic diversity and evolution of these clones by analyzing 78 DFT1 and 41 DFT2 genomes relative to a newly assembled, chromosome-level reference. Time-resolved phylogenetic trees reveal that DFT1 first emerged in 1986 (1982 to 1989) and DFT2 in 2011 (2009 to 2012). Subclone analysis documents transmission of heterogeneous cell populations. DFT2 has faster mutation rates than DFT1 across all variant classes, including substitutions, indels, rearrangements, transposable element insertions, and copy number alterations, and we identify a hypermutated DFT1 lineage with defective DNA mismatch repair. Several loci show plausible evidence of positive selection in DFT1 or DFT2, including loss of chromosome Y and inactivation of MGA, but none are common to both cancers. This study reveals the parallel long-term evolution of two transmissible cancers inhabiting a common niche in Tasmanian devils.
| S-EPMC7614631 | biostudies-literature
Project description:Clonally transmissible cancers are somatic cell lineages that are spread between individuals via the transfer of living cancer cells. There are only three known naturally occurring transmissible cancers, and these affect dogs, soft-shell clams, and Tasmanian devils, respectively. The Tasmanian devil transmissible facial cancer was first observed in 1996, and is threatening its host species with extinction. Until now, this disease has been consistently associated with a single aneuploid cancer cell lineage that we refer to as DFT1. Here we describe a second transmissible cancer, DFT2, in five devils located in southern Tasmania in 2014 and 2015. DFT2 causes facial tumors that are grossly indistinguishable but histologically distinct from those caused by DFT1. DFT2 bears no detectable cytogenetic similarity to DFT1 and carries a Y chromosome, which contrasts with the female origin of DFT1. DFT2 shows different alleles to both its hosts and DFT1 at microsatellite, structural variant, and major histocompatibility complex (MHC) loci, confirming that it is a second cancer that can be transmitted between devils as an allogeneic, MHC-discordant graft. These findings indicate that Tasmanian devils have spawned at least two distinct transmissible cancer lineages and suggest that transmissible cancers may arise more frequently in nature than previously considered. The discovery of DFT2 presents important challenges for the conservation of Tasmanian devils and raises the possibility that this species is particularly prone to the emergence of transmissible cancers. More generally, our findings highlight the potential for cancer cells to depart from their hosts and become dangerous transmissible pathogens.
| S-EPMC4720317 | biostudies-literature
Project description:Emerging infectious diseases are rising globally and understanding host-pathogen interactions during the initial stages of disease emergence is essential for assessing potential evolutionary dynamics and designing novel management strategies. Tasmanian devils (Sarcophilus harrisii) are endangered due to a transmissible cancer-devil facial tumour disease (DFTD)-that since its emergence in the 1990s, has affected most populations throughout Tasmania. Recent studies suggest that devils are adapting to the DFTD epidemic and that disease-induced extinction is unlikely. However, in 2014, a second and independently evolved transmissible cancer-devil facial tumour 2 (DFT2)-was discovered at the d'Entrecasteaux peninsula, in south-east Tasmania, suggesting that the species is prone to transmissible cancers. To date, there is little information about the distribution, epidemiology and effects of DFT2 and its interaction with DFTD. Here, we use data from monitoring surveys and roadkills found within and adjacent to the d'Entrecasteaux peninsula to determine the distribution of both cancers and to compare their epidemiological patterns. Since 2012, a total of 51 DFTD tumours have been confirmed among 26 individuals inside the peninsula and its surroundings, while 40 DFT2 tumours have been confirmed among 23 individuals, and two individuals co-infected with both tumours. All devils with DFT2 were found within the d'Entrecasteaux peninsula, suggesting that this new transmissible cancer is geographically confined to this area. We found significant differences in tumour bodily location in DFTD and DFT2, with non-facial tumours more commonly found in DFT2. There was a significant sex bias in DFT2, with most cases reported in males, suggesting that since DFT2 originated from a male host, females might be less susceptible to this cancer. We discuss the implications of our results for understanding the epidemiological and evolutionary interactions of these two contemporary transmissible cancers and evaluating the effectiveness of potential management strategies.
| S-EPMC6752152 | biostudies-other
Project description:The evolution of two transmissible cancers in Tasmanian devils (2023).
| PRJEB51704 | ENA
Project description: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.
| S-EPMC5013612 | biostudies-literature
Project description:Devil facial tumour 1 (DFT1) is a transmissible cancer clone endangering the Tasmanian devil. The expansion of DFT1 across Tasmania has been documented, but little is known of its evolutionary history. We analysed genomes of 648 DFT1 tumours collected throughout the disease range between 2003 and 2018. DFT1 diverged early into five clades, three spreading widely and two failing to persist. One clade has replaced others at several sites, and rates of DFT1 coinfection are high. DFT1 gradually accumulates copy number variants (CNVs), and its telomere lengths are short but constant. Recurrent CNVs reveal genes under positive selection, sites of genome instability, and repeated loss of a small derived chromosome. Cultured DFT1 cell lines have increased CNV frequency and undergo highly reproducible convergent evolution. Overall, DFT1 is a remarkably stable lineage whose genome illustrates how cancer cells adapt to diverse environments and persist in a parasitic niche.
| S-EPMC7685465 | biostudies-literature
Project description:Maintenance of adaptive genetic variation has long been a goal of management of natural populations, but only recently have genomic tools allowed identification of specific loci associated with fitness-related traits in species of conservation concern. This raises the possibility of managing for genetic variation directly relevant to specific threats, such as those due to climate change or emerging infectious disease. Tasmanian devils (Sarcophilus harrisii) face the threat of a transmissible cancer, devil facial tumor disease (DFTD), that has decimated wild populations and led to intensive management efforts. Recent discoveries from genomic and modeling studies reveal how natural devil populations are responding to DFTD, and can inform management of both captive and wild devil populations. Notably, recent studies have documented genetic variation for disease-related traits and rapid evolution in response to DFTD, as well as potential mechanisms for disease resistance such as immune response and tumor regression in wild devils. Recent models predict dynamic persistence of devils with or without DFTD under a variety of modeling scenarios, although at much lower population densities than before DFTD emerged, contrary to previous predictions of extinction. As a result, current management that focuses on captive breeding and release for maintaining genome-wide genetic diversity or demographic supplementation of populations could have negative consequences. Translocations of captive devils into wild populations evolving with DFTD can cause outbreeding depression and/or increases in the force of infection and thereby the severity of the epidemic, and we argue that these risks outweigh any benefits of demographic supplementation in wild populations. We also argue that genetic variation at loci associated with DFTD should be monitored in both captive and wild populations, and that as our understanding of DFTD-related genetic variation improves, considering genetic management approaches to target this variation is warranted in developing conservation strategies for Tasmanian devils.
| S-EPMC6759055 | biostudies-literature
Project description: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.
| S-EPMC6759049 | biostudies-literature
Project description:1. Monitoring the response of wild mammal populations to threatening processes is fundamental to effective conservation management. This is especially true for infectious diseases, which may have dynamic and therefore unpredictable interactions with their host. 2. We investigate the long-term impact of a transmissible cancer, devil facial tumour disease (DFTD), on the endemic Tasmanian devil. We analyse trends in devil spot-light counts and density across the area impacted by the disease. We investigate the demographic parameters which might be driving these trends, and use spatial capture-recapture models to examine whether DFTD has affected home range size. 3. We found that devils have declined by an average of 77% in areas affected by DFTD, and that there is a congruent trend of ongoing small decline in spotlight counts and density estimates. Despite this, devils have persisted to date within each of nine monitoring sites. One site is showing as yet unexplained small increases in density 8-10 years after the emergence of DFTD. 4. We also found the prevalence of DFTD has not abated despite large declines in density and that diseased sites continue to be dominated by young devils. The long-term impact of the disease has been partially offset by increased fecundity in the form of precocial breeding in 1-year-old females, and more pouch young per female in diseased sites. The lower densities resulting from DFTD did not affect home range size. 5. Synthesis and applications. Transmission of devil facial tumour disease continues despite large declines in devil density over multiple generations. Plasticity in life history traits has ameliorated the impact of devil facial tumour disease, however broad-scale trends in density show ongoing decline. In light of this, devil facial tumour disease and the impact of stochastic events on the reduced densities wrought by the disease, continue to threaten devils. In the absence of methods to manage disease in wild populations, we advocate managing the low population densities resulting from disease rather than disease per se.
| S-EPMC6078421 | biostudies-literature
Project description:Devil facial tumour disease 1 and 2 (DFT1 and DFT2) are two genetically distinct transmissible cancers endangering the survival of the Tasmanian devil (Sarcophilus harrisii). DFT1 first arose from a cell of the Schwann cell lineage, however, the tissue-of-origin of the recently discovered DFT2 cancer remains unknown. Here we have performed mRNA and protein expression analyses to show that variation in expression patterns between DFT1 and DFT2 tumours is low. Furthermore, DFT2 cells express a range of markers associated with Schwann cell differentiation, suggesting a similar tissue-of-origin to DFT1 tumours. These findings suggest that devils may be predisposed to transmissible cancers of Schwann cell origin. The emergence of these two unique cancers presents an unprecedented opportunity to gain insight into cancer development in animal species.
2019-08-06 | PXD011209 | Pride