Evolution in a transmissible cancer: a study of the chromosomal changes in devil facial tumor (DFT) as it spreads through the wild Tasmanian devil population (original) (raw)
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The devil is in the details: Genomics of transmissible cancers in Tasmanian devils
Cancer poses one of the greatest human health threats of our time. Fortunately, aside from a few rare cases of cancer transmission in immune-suppressed organ transplant recipients or a small number of transmission events from mother to fetus [2], cancers are not spread from human to human. However, transmissible cancers have been detected in vertebrate and invertebrate animals, sometimes with devastating effects . Four examples of transmissible cancers are now known: 1) canine transmissible venereal tumor (CTVT) in dogs , 2) a tumor in a laboratory population of Syrian hamsters that is no longer cultured , 3) infectious neoplasias in at least four species of bivalve mollusks , and 4) two independently derived transmissible cancers (devil facial tumor disease [DFTD]) in Tasmanian devils [7-10] . The etiologic agents of CTVT [4], the bivalve cancers , and DFTD [7] are the transplants (allografts) of the neoplastic cells themselves, but the etiologic agent is unknown for the hamster tumor.
Rapid evolutionary response to a transmissible cancer in Tasmanian devils
Nature Communications, 2016
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.
The Origins and Vulnerabilities of Two Transmissible Cancers in Tasmanian Devils
Cancer cell, 2018
Transmissible cancers are clonal lineages that spread through populations via contagious cancer cells. Although rare in nature, two facial tumor clones affect Tasmanian devils. Here we perform comparative genetic and functional characterization of these lineages. The two cancers have similar patterns of mutation and show no evidence of exposure to exogenous mutagens or viruses. Genes encoding PDGF receptors have copy number gains and are present on extrachromosomal double minutes. Drug screening indicates causative roles for receptor tyrosine kinases and sensitivity to inhibitors of DNA repair. Y chromosome loss from a male clone infecting a female host suggests immunoediting. These results imply that Tasmanian devils may have inherent susceptibility to transmissible cancers and present a suite of therapeutic compounds for use in conservation.
A second transmissible cancer in Tasmanian devils
Proceedings of the National Academy of Sciences, 2015
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, a...
Anthropogenic selection enhances cancer evolution in Tasmanian devil tumours
Evolutionary Applications, 2014
The Tasmanian Devil Facial Tumour Disease (DFTD) provides a unique opportunity to elucidate the long-term effects of natural and anthropogenic selection on cancer evolution. Since first observed in 1996, this transmissible cancer has caused local population declines by >90%. So far, four chromosomal DFTD variants (strains) have been described and karyotypic analyses of 253 tumours showed higher levels of tetraploidy in the oldest strain. We propose that increased ploidy in the oldest strain may have evolved in response to effects of genomic decay observed in asexually reproducing organisms. In this study, we focus on the evolutionary response of DFTD to a disease suppression trial. Tumours collected from devils subjected to the removal programme showed accelerated temporal evolution of tetraploidy compared with tumours from other populations where no increase in tetraploid tumours were observed. As ploidy significantly reduces tumour growth rate, we suggest that the disease suppression trial resulted in selection favouring slower growing tumours mediated by an increased level of tetraploidy. Our study reveals that DFTD has the capacity to rapidly respond to novel selective regimes and that disease eradication may result in novel tumour adaptations, which may further imperil the long-term survival of the world's largest carnivorous marsupial.
PLoS Genetics, 2012
Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD.
PLoS genetics, 2012
Devil facial tumour disease (DFTD) is a fatal, transmissible malignancy that threatens the world's largest marsupial carnivore, the Tasmanian devil, with extinction. First recognised in 1996, DFTD has had a catastrophic effect on wild devil numbers, and intense research efforts to understand and contain the disease have since demonstrated that the tumour is a clonal cell line transmitted by allograft. We used chromosome painting and gene mapping to deconstruct the DFTD karyotype and determine the chromosome and gene rearrangements involved in carcinogenesis. Chromosome painting on three different DFTD tumour strains determined the origins of marker chromosomes and provided a general overview of the rearrangement in DFTD karyotypes. Mapping of 105 BAC clones by fluorescence in situ hybridisation provided a finer level of resolution of genome rearrangements in DFTD strains. Our findings demonstrate that only limited regions of the genome, mainly chromosomes 1 and X, are rearranged in DFTD. Regions rearranged in DFTD are also highly rearranged between different marsupials. Differences between strains are limited, reflecting the unusually stable nature of DFTD. Finally, our detailed maps of both the devil and tumour karyotypes provide a physical framework for future genomic investigations into DFTD.
Two decades of the impact of Tasmanian Devil Facial Tumour Disease (DFTD)
Integrative and comparative biology, 2018
The Tasmanian Devil, a marsupial carnivore, has been restricted to the island state of Tasmania since its extinction on the Australian mainland about three thousand years ago. In the past two decades, this species has experienced severe population decline due to the emergence of devil facial tumour disease (DFTD), a transmissible cancer. During these twenty years, scientists have puzzled over the immunological and evolutionary responses by the Tasmanian devil to this transmissible cancer. Targeted strategies in population management and disease control have been developed as well as comparative processes to identify variation in tumor and host genetics. A multi-disciplinary approach with multi-institutional teams has produced considerable advances over the last decade. This has led to a greater understanding of the molecular pathogenesis and genomic classification of this cancer. New and promising developments in the Tasmanian devil's story include evidence that most immunized, ...
Marsupial Genetics and Genomics, 2010
The Tasmanian devil (Sarcophilus harrisii), so named for its blood-curdling, nocturnal shrieks and snarls, is the largest of the carnivorous marsupials. Although once widely persecuted, concerted efforts are now being made to save the devil from extinction following the emergence of a fatal transmissible malignancy known as devil facial tumour disease (DFTD). DFTD is unusual in that the infectious agent is the cancer cell itself. This chapter discusses the aetiology and pathogenesis of DFTD as well as the profound impact the spread of DFTD has had on the devil's conservation status. Strategies for managing DFTD and conserving the devil will be explored and the contribution of new sequencing technology to the field of conservation genetics and genomics will be examined with regard to the Tasmanian devil and DFTD. Keywords Tasmanian devil • Devil facial tumour disease • Wildlife disease • Conservation genetics • Genomics 23.1 The Tasmanian Devil and the Emergence of DFTD The Tasmanian devil (Sarcophilus harrisii), is the largest of the Dasyuridae, a speciose and morphologically diverse family of carnivorous marsupials that are represented in most terrestrial habitats in Australia and New Guinea (Crowther and Blacket, 2003). S. harrisii diverged in the mid Miocene, approximately 12.4 million years ago, and originally thrived on the Australian mainland (Krajewski et al., 2000). Tasmanian populations were separated from their mainland conspecifics after the formation of the Bass Strait 14,000 years ago (Lambeck and Chappell, 2001). Now the devil is confined to the island state; their extinction on mainland Australia