Examinando por Autor "Metzger, Michael J."
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Ítem A single clonal lineage of transmissible cancer identified in two marine mussel species in South America and Europe(eLife, 2019-11-08) Yonemitsu, Marisa A.; Giersch, Rachael M.; Polo-Prieto, Maria; Hammel, Maurine; Simon, Alexis; Cremonte, Florencia; Avilés, Fernando T.; Merino-Véliz, Nicolás; Burioli, Erika A.V.; Muttray, Annette F.; Sherry, James; Reinisch, Carol; Baldwin, Susan A.; Goff, Stephen P.; Houssin, Maryline; Arriagada, Gloria; Vázquez, Nuria; Bierne, Nicolas; Metzger, Michael J.Transmissible cancers, in which cancer cells themselves act as an infectious agent, have been identified in Tasmanian devils, dogs, and four bivalves. We investigated a disseminated neoplasia affecting geographically distant populations of two species of mussels (Mytilus chilensis in South America and M. edulis in Europe). Sequencing alleles from four loci (two nuclear and two mitochondrial) provided evidence of transmissible cancer in both species. Phylogenetic analysis of cancer-associated alleles and analysis of diagnostic SNPs showed that cancers in both species likely arose in a third species of mussel (M. trossulus), but these cancer cells are independent from the previously identified transmissible cancer in M. trossulus from Canada. Unexpectedly, cancers from M. chilensis and M. edulis are nearly identical, showing that the same cancer lineage affects both. Thus, a single transmissible cancer lineage has crossed into two new host species and has been transferred across the Atlantic and Pacific Oceans and between the Northern and Southern hemispheresÍtem Activation of transcription and retrotransposition of a novel retroelement, Steamer, in neoplastic hemocytes of the mollusk Mya arenaria(National Academy of Sciences, 2014-09) Arriagada, Gloria; Metzger, Michael J.; Muttray, Annette F.; Sherry, James; Reinisch, Carol; Street, Craig; Lipkin, W. Ian; Goff, Stephen P.Bivalve mollusks of the North Atlantic, most prominently the soft shell clam Mya arenaria, are afflicted with an epidemic transmissible disease of the circulatory system closely resembling leukemia. The disease is characterized by a dramatic expansion of blast-like cells in the hemolymph with high mitotic index. Examination of hemolymph of diseased clams revealed high levels of reverse transcriptase activity, the hallmark of retroviruses and retroelements. By deep sequencing of RNAs from hemolymph, we identified transcripts of a novel retroelement, here named Steamer. The DNA of the element is marked by long terminal repeats and encodes a single large protein with similarity to mammalian retroviral Gag-Pol proteins. Steamer mRNA levels were specifically elevated in diseased hemocytes, and high expression was correlated with disease status. DNA copy number per genome was present at enormously high levels in diseased hemocytes, indicative of extensive reverse transcription and retrotransposition. Steamer activation in M. arenaria is an example of a catastrophic induction of genetic instability that may initiate or advance the course of leukemia.Ítem Centuries of genome instability and evolution in soft-shell clam, Mya arenaria, bivalve transmissible neoplasia(Nature Research, 2023-11) Hart, Samuel F. M.; Yonemitsu, Marisa A.; Giersch, Rachael M.; Garrett, Fiona E. S.; Beal, Brian F.; Arriagada, Gloria; Davis, Brian W.; Ostrander, Elaine A.; Goff, Stephen P.; Metzger, Michael J.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. © 2023, The Author(s)Ítem Identification and expression analysis of two steamer-like retrotransposons in the Chilean blue mussel (Mytilus chilensis)(Biological Research, Volume 57, Issue 1December 2024 Article number 17, 2024-12) Arriagada, Gloria; Quezada, Johan; Merino-Veliz, Nicolas; Avilés, Fernando; Tapia-Cammas, Diana; Gomez, Jorge; Curotto, Daniela; Valdes, Juan A.; Oyarzún, Pablo A.; Gallardo-Escárate, Cristian; Metzger, Michael J.; Alvarez, MarcoBackground: Disseminated neoplasia (DN) is a proliferative cell disorder of the circulatory system of bivalve mollusks. The disease is transmitted between individuals and can also be induced by external chemical agents such as bromodeoxyuridine. In Mya arenaria, we have cloned and characterized an LTR-retrotransposon named Steamer. Steamer mRNA levels and gene copy number correlates with DN and can be used as a marker of the disease. So far, the only mollusk where a retrotransposon expression relates to DN is Mya arenaria. On the other hand, it has been reported that the Chilean blue mussel Mytilus chilensis can also suffers DN. Our aim was to identify retrotransposons in Mytilus chilensis and to study their expression levels in the context of disseminated neoplasia. Results: Here we show that 7.1% of individuals collected in August 2018, from two farming areas, presents morphological characteristics described in DN. Using Steamer sequence to interrogate the transcriptome of M. chilensis we found two putative retrotransposons, named Steamer-like elements (MchSLEs). MchSLEs are present in the genome of M. chilensis and MchSLE1 is indeed an LTR-retrotransposon. Neither expression, nor copy number of the reported MchSLEs correlate with DN status but both are expressed at different levels among individual animals. We also report that in cultured M. chilensis haemocytes MchSLEs1 expression can be induced by bromodeoxyuridine. Conclusions: We conclude that SLEs present in Mytilus chilensis are differentially expressed among individuals and do not correlate with disseminated neoplasia. Treatment of haemocytes with a stressor like bromodeoxyuridine induces expression of MchSLE1 suggesting that in Mytilus chilensis environmental stressors can induce activation of LTR-retrotransposon. © The Author(s) 2024.