Figure - available from: Nature Cancer
This content is subject to copyright. Terms and conditions apply.
Distribution of repetitive elements in the cockle genome Frequency of classifiable repeats (26% of all repeats) along the reference cockle genome, displayed in terms of number of copies per 100-kb genomic segment. Repetitive element types with more than 1000 annotated copies are represented: long interspersed nuclear elements (LINE, 172,722 copies, 33.0%), transfer RNA repeats (tRNA, 81,766 copies, 15.6%), long terminal repeat elements (LTR, 78,009 copies, 14.9%), simple repeats (70,016 copies, 13.3%), short interspersed nuclear elements (SINE, 55,434 copies, 10.6%), DNA repeat elements (42,917 copies, 8.2%), low complexity repeats (12,171 copies, 2.3%), rolling circle repeats (RC, 8,843 copies, 1.7%), satellite repeats (2,100 copies, 0.4%). Genomic segments along the ideogram are classified as GC-low or GC-high based on whether their average nucleotide content is below or above the estimated average genomic G+C content (35.6%). Source data
Source publication
Transmissible cancers are malignant cell lineages that spread clonally between individuals. Several such cancers, termed bivalve transmissible neoplasia (BTN), induce leukemia-like disease in marine bivalves. This is the case of BTN lineages affecting the common cockle, Cerastoderma edule, which inhabits the Atlantic coasts of Europe and northwest...
Similar publications
The goal of this research is to acquire new information on the distribution of bivalves along the Iraqi coastline. Between 2020 and 2021, new records of marine bivalves, Sheldonella lateralis (Reeve, 1844) and Periglypta crispata (Deshayes, 1854) were discovered near the Iraqi coast in the northwestern Persian-Arabian Gulf.
Citations
... Characterization and evolution of transposable elements (TE) Genomic structure analysis revealed that the T. maxima genome has a notably higher proportion of repetitive elements (68.07% of its 1.32-Gb genome) compared to other bivalve species. For example, the 755.5-Mb assembled genome of a closely related cardiid Cerastoderma edule contains 37.81% repetitive elements 29 (Table 2). Given that the non-repetitive genomic regions in the two species are relatively similar in size (421 and 469 Mb respectively), it clearly points to repetitive elements as the main driver of larger genome size in T. maxima. ...
Symbioses are major drivers of organismal diversification and phenotypic innovation. However, how long-term symbioses shape whole genome evolution in metazoans is still underexplored. Here, we use a giant clam (Tridacna maxima) genome to demonstrate how symbiosis has left complex signatures in an animal’s genome. Giant clams thrive in oligotrophic waters by forming a remarkable association with photosymbiotic dinoflagellate algae. Genome-based demographic inferences uncover a tight correlation between T. maxima global population change and major paleoclimate and habitat shifts, revealing how abiotic and biotic factors may dictate T. maxima microevolution. Comparative analyses reveal genomic features that may be symbiosis-driven, including expansion and contraction of immunity-related gene families and a large proportion of lineage-specific genes. Strikingly, about 70% of the genome is composed of repetitive elements, especially transposable elements, most likely resulting from a symbiosis-adapted immune system. This work greatly enhances our understanding of genomic drivers of symbiosis that underlie metazoan evolution and diversification.
... Additionally, two BTN lineages (CedBTN1 and CedBTN2) have been detected infecting C. edule along the Atlantic coast of Europe. Phylogenetic analyses of somatic and germinal structural variants from whole-genomes of CedBTN1 and CedBTN2 have detected two origins (Bruzos et al., 2023) as suggested by the study of microsatellites and the mitochondrial cytochrome c oxidase subunit I gene (Metzger et al. 2015). Analysis of the mitogenome has revealed nine events of mitochondrial capture by CedBTN from its hosts: up to six captures have been detected in CedBTN1 and three captures in CedBTN2 (Bruzos et al., 2023). ...
... Phylogenetic analyses of somatic and germinal structural variants from whole-genomes of CedBTN1 and CedBTN2 have detected two origins (Bruzos et al., 2023) as suggested by the study of microsatellites and the mitochondrial cytochrome c oxidase subunit I gene (Metzger et al. 2015). Analysis of the mitogenome has revealed nine events of mitochondrial capture by CedBTN from its hosts: up to six captures have been detected in CedBTN1 and three captures in CedBTN2 (Bruzos et al., 2023). CedBTN1 and CedBTN2 share common characteristics of disseminated neoplasia, large cells with a round or oval shape and a high nucleus:cytoplasm ratio with prominent nucleoli and a high frequency of mitotic figures (Carballal et al., 2015). ...
... CedBTN1 and CedBTN2 share common characteristics of disseminated neoplasia, large cells with a round or oval shape and a high nucleus:cytoplasm ratio with prominent nucleoli and a high frequency of mitotic figures (Carballal et al., 2015). The copy number distributions observed in neoplastic cells of both lineages typically exhibited a modal CN of 4.0, implying ancestral tetraploidy (Bruzos et al., 2023). They are observed in the connective tissue of multiple organs and in vessels and sinuses of the circulatory system (Carballal et al., 2015). ...
... Initial screens for host-to-tumour DNA exchange in transmissible cancers detected numerous instances of mitochondrial genome (mtDNA) horizontal transfer 16,[22][23][24][25] . Indeed, the repeated observation of mtDNA capture in transmissible cancers has lent credibility to the idea that exchange of mtDNA between somatic cells is not an uncommon occurrence in multicellular organisms 26 . ...
Although somatic cell genomes are usually entirely clonally inherited, nuclear DNA exchange between cells of an organism can occur sporadically by cell fusion, phagocytosis or other mechanisms. This phenomenon has long been noted in the context of cancer, where it could be envisaged that DNA horizontal transfer plays a functional role in disease evolution. However, an understanding of the frequency and significance of this process in naturally occurring tumours is lacking. The host-tumour genetic discordance of transmissible cancers, malignant clones which pass between animals as allogeneic grafts, provides an opportunity to investigate this. We screened for host-to-tumour horizontal transfer of nuclear DNA in 174 tumours from three transmissible cancers affecting dogs and Tasmanian devils, and detected a single instance in the canine transmissible venereal tumour (CTVT). This involved introduction of a 15-megabase dicentric genetic element, composed of 11 rearranged fragments of six chromosomes, to a CTVT sublineage occurring in Asia around 2,000 years ago. The element forms the short arm of a small submetacentric chromosome, and derives from a dog with ancestry associated with the ancient Middle East. The introduced DNA fragment is transcriptionally active and has adopted the expression profile of CTVT. Its 143 genes do not, however, confer any obvious advantage to its spatially restricted CTVT sublineage. Our findings indicate that nuclear DNA horizontal transfer, although likely a rare event in tumour evolution, provides a viable mechanism for the acquisition of genetic material in naturally occurring cancer genomes.
... Transmissible cancers defy all conventional thinking, as they involve neoplastic cells spreading between individuals beyond their original host (Murchison 2008) either through direct contact, as in the canine venereal tumour or the Tasmanian devil facial tumour (Murgia et al. 2006;Murchison et al. 2012) or by the absorption of cells freed to the media, as in hemic neoplasia in bivalves (Metzger et al. 2015(Metzger et al. , 2016Bruzos et al. 2023;Hart et al. 2023). Nowadays, this phenomenon extends to, at least, six bivalve species (Metzger et al. 2015;Hart et al. 2023), among which, the common cockle, Cerastoderma edule, exhibits two transmissible cancer lineages, differentiated by cytological and genomic features (Bruzos et al. 2023). ...
... Transmissible cancers defy all conventional thinking, as they involve neoplastic cells spreading between individuals beyond their original host (Murchison 2008) either through direct contact, as in the canine venereal tumour or the Tasmanian devil facial tumour (Murgia et al. 2006;Murchison et al. 2012) or by the absorption of cells freed to the media, as in hemic neoplasia in bivalves (Metzger et al. 2015(Metzger et al. , 2016Bruzos et al. 2023;Hart et al. 2023). Nowadays, this phenomenon extends to, at least, six bivalve species (Metzger et al. 2015;Hart et al. 2023), among which, the common cockle, Cerastoderma edule, exhibits two transmissible cancer lineages, differentiated by cytological and genomic features (Bruzos et al. 2023). These neoplasias are evolutionary relics, accumulating mutations over time (Bruzos et al. 2023;Hart et al. 2023) and thus constitute unique models of tumour dynamics, Communicated by Martine Collart. ...
... Nowadays, this phenomenon extends to, at least, six bivalve species (Metzger et al. 2015;Hart et al. 2023), among which, the common cockle, Cerastoderma edule, exhibits two transmissible cancer lineages, differentiated by cytological and genomic features (Bruzos et al. 2023). These neoplasias are evolutionary relics, accumulating mutations over time (Bruzos et al. 2023;Hart et al. 2023) and thus constitute unique models of tumour dynamics, Communicated by Martine Collart. ...
Cancer is a multifaceted genetic disease characterized by the acquisition of several essential hallmarks. Notably, certain cancers exhibit horizontal transmissibility, observed across mammalian species and diverse bivalves, the latter referred to as hemic neoplasia. Within this complex landscape, epigenetic mechanisms such as histone modifications and cytosine methylation emerge as fundamental contributors to the pathogenesis of these transmissible cancers. Our study delves into the epigenetic landscape of Cerastoderma edule, focusing on whole-genome methylation and hydroxymethylation profiles in heathy specimens and transmissible neoplasias by means of Nanopore long-read sequencing. Our results unveiled a global hypomethylation in the neoplastic specimens compared to their healthy counterparts, emphasizing the role of DNA methylation in these tumorigenic processes. Furthermore, we verified that intragenic CpG methylation positively correlated with gene expression, emphasizing its role in modulating transcription in healthy and neoplastic cockles, as also highlighted by some up-methylated oncogenic genes. Hydroxymethylation levels were significantly more elevated in the neoplastic samples, particularly within satellites and complex repeats, likely related to structural functions. Additionally, our analysis also revealed distinct methylation and activity patterns in retrotransposons, providing additional insights into bivalve neoplastic processes. Altogether, these findings contribute to understanding the epigenetic dynamics of bivalve neoplasias and shed light on the roles of DNA methylation and hydroxymethylation in tumorigenesis. Understanding these epigenetic alterations holds promise for advancing our broader understanding of cancer epigenetics.
... Another mechanism that may accelerate evolution and select for advantageous traits is the horizontal uptake by cancer cells of host mitochondrial DNA, as previously observed in CTVT 14 . Bruzos et al. 6 showed that the transmissible cancer lineages in C. edule acquired mitochondria from their transient hosts over time. This mechanism could contribute to the genomic plasticity, long-term survival and transmission of these transmissible cancer lineages, and led to the discovery of their remarkable geographical spread from Portugal to Denmark and Norway. ...
... The research findings by Bruzos et al. 6 and Hart et al. 7 conclusively delineate the evolution of transmissible cancers in bivalve mollusks, enhancing our understanding of how they spread across oceans and survive for hundreds of years. These characteristics indicate the remarkable robustness of these cancer cells and could pose a substantial risk to bivalve mollusk populations. ...
... Two studies in this issue of Nature Cancer set out to elucidate the origin and evolution of BTN in two edible mollusks. Bruzos et al. 6 performed in-depth genetic characterizations of 61 cases of BTN in the common cockle Cerastoderma edule, which inhabits the Atlantic coasts of Europe and northwest Africa. Hart et al. 7 conducted their research on the soft-shell clam Mya arenaria using eight diseased animals found on the east coast of North America. ...
Transmissible cancer affects marine bivalve mollusks worldwide, but how genetic mechanisms influence cancer evolution and disease spread remains largely unexplored. Two new studies provide insights into the ancient origin of founder clones and the long-term tolerance of contagious cancer cells to extreme genome instability.
... Our analysis of the MarBTN genome is presented simultaneously to an independent analysis of two lineages in the common cockle (Cerastoderma edule) or CedBTN, by Bruzos and colleagues 57 . CedBTN infection presents as a similar leukemia-like disseminated neoplasia phenotype to MarBTN and gene expression points toward a hemocyte origin for BTN in both species. ...
Transmissible cancers are infectious parasitic clones that metastasize to new hosts, living past the death of the founder animal in which the cancer initiated. We investigated the evolutionary history of a cancer lineage that has spread though the soft-shell clam (Mya arenaria) population by assembling a chromosome-scale soft-shell clam reference genome and characterizing somatic mutations in transmissible cancer. We observe high mutation density, widespread copy-number gain, structural rearrangement, loss of heterozygosity, variable telomere lengths, mitochondrial genome expansion and transposable element activity, all indicative of an unstable cancer genome. We also discover a previously unreported mutational signature associated with overexpression of an error-prone polymerase and use this to estimate the lineage to be >200 years old. Our study reveals the ability for an invertebrate cancer lineage to survive for centuries while its genome continues to structurally mutate, likely contributing to the evolution of this lineage as a parasitic cancer.
Transmissible cancers are unique instances in which cancer cells escape their original host and spread through a population as a clonal lineage, documented in Tasmanian Devils, dogs, and ten bivalve species. For a cancer to repeatedly transmit to new hosts, these lineages must evade strong barriers to transmission, notably the metastasis-like physical transfer to a new host body and rejection by that host's immune system. We quantified gene expression in a transmissible cancer lineage that has spread through the soft-shell clam (Mya arenaria) population to investigate potential drivers of its success as a transmissible cancer lineage, observing extensive differential expression of genes and gene pathways. We observed upregulation of genes involved with genotoxic stress response, ribosome biogenesis and RNA processing, and downregulation of genes involved in tumor suppression, cell adhesion, and immune response. We also observe evidence that widespread genome instability affects the cancer transcriptome via gene fusions, copy number variation, and transposable element insertions. Finally, we incubated cancer cells in seawater, the presumed host-to-host transmission vector, and observed conserved responses to halt metabolism, avoid apoptosis and survive the low-nutrient environment. Interestingly, many of these responses are also present in healthy clam cells, suggesting that bivalve hemocytes may have inherent seawater survival responses that may partially explain why transmissible cancers are so common in bivalves. Overall, this study reveals multiple mechanisms this lineage may have evolved to successfully spread through the soft-shell clam population as a contagious cancer, utilizing pathways known to be conserved in human cancers as well as pathways unique to long-lived transmissible cancers.
Evolutionary theory predicts that accumulation of deleterious mutations in asexually reproducing organisms should lead to genomic decay. Clonally reproducing cell lines, i.e., transmissible cancers, when cells are transmitted as allografts/xenografts, break these rules, and survive for centuries and millennia. The currently known 11 transmissible cancer lineages occur in dogs (Canine Venereal Tumour Disease, CTVT), in Tasmanian devils (Devil Facial Tumour Diseases, DFT 1 and DFT2) and in bivalves (bivalve transmissible neoplasia, BTN). Despite the mutation loads of these cell lines being much higher than observed in human cancers, they have not been eliminated in space and time.
Here we provide potential explanations how these fascinating cell lines may have overcome the fitness decline due to the progressive accumulation of deleterious mutations and propose that the high mutation load may carry an indirect positive fitness outcome. We offer ideas on how these host-pathogen systems could be used to answer outstanding questions in evolutionary biology.
The recent studies on the evolution of these clonal pathogens reveal key mechanistic insight into transmissible cancer genomes, information that is essential for future studies investigating how these contagious cancer cell lines can repeatedly evade immune recognition, evolve, and survive in the landscape of highly diverse hosts.
Cancer is a disease that occurs when cells multiply uncontrollably. It can affect species on land or in water. Normally, cancer is not contagious; it only affects the organism in which it originates. However, recently, a new type of contagious cancer was found in some ocean animals. Contagious cancers have been discovered in clams, cockles, and mussels around the world. These cancer cells leave the body of the organism where they originated, survive in seawater, and then infect other individuals. In this article, we will tell you what makes contagious cancers different from normal cancers, the species in which contagious cancers have been detected, and the great importance of studying these rare cancers.
