[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-332081-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-332081-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","the-molecular-evolution-of-cancer-associated-genes-in-mammals","The molecular evolution of cancer associated genes in mammals","","Cancer has persisted across millions of years of mammalian evolution, yet cancer mortality risk and selection pressures differ among mammalian orders. This study investigates evolutionary histories of cancer-associated gene sequences across 384 mammalian taxa, assessing selection signatures in oncogenes, tumour suppressors, and immune genes using comparative genomic and phylogenetic analyses. Results show broad concordance between gene evolution and species evolution, with distinct patterns of conserved oncogenes and episodic diversifying selection, including site-specific opposing selection pressures in bat Casp8 domains.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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study?","Question",{"text":63,"@type":64},"The study analyzes oncogenes, tumour suppressor genes, and immune genes, including specific examples such as GRB2, FGL2, CDC42, LITAF, Casp8, BRCA2, IL2, CD274, and B2M.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"Do cancer-associated genes generally evolve alongside species evolution?",{"text":68,"@type":64},"Phylogenetic results indicate that, for most species, the evolution of cancer-associated genes follows the species’ evolutionary history.",{"name":70,"@type":61,"acceptedAnswer":71},"What was found about Casp8 selection in bats?",{"text":72,"@type":64},"Site-specific selection analyses show that the two apoptosis-associated domains of the Casp8 gene in bats are under opposing selection forces, with positive selection on one domain and negative selection on the 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molecular evolution of cancer associated genes in mammals  \nNick MacDonald1, Nynke Raven1,6, Wendy Diep1, Samantha Evans1, Senuri Pannipitiya1, Georgina Bramwell1, Caitlin Vanbeek1, Frédéric Thomas2,3, Tracey Russell4,  \nAntoine M. Dujon1, MarinaTelonis‑Scott5 & Beata Ujvari1,6*  \nCancer is a disease that many multicellular organisms have faced for millions of years, and species have evolved various tumour suppression mechanisms to control oncogenesis. Although cancer occurs across the tree of life, cancer related mortality risks vary across mammalian orders, with Carnivorans particularly affected. Evolutionary theory predicts different selection pressures on genes associated with cancer progression and suppression, including oncogenes, tumour suppressor genes and immune genes. Therefore, we investigated the evolutionary history of cancer associated gene sequences across 384 mammalian taxa, to detect signatures of selection across categories of oncogenes (GRB2, FGL2 and CDC42), tumour suppressors (LITAF, Casp8 and BRCA2) and immune genes (IL2, CD274 and B2M) . This approach allowed us to conduct a fine scale analysis of gene wide and site‑specific signatures of selection across mammalian lineages under the lens of cancer susceptibility. Phylogenetic analyses revealed that for most species the evolution of cancer associated genes follows the species’ evolution. The gene wide selection analyses revealed oncogenes being the most conserved, tumour suppressor and immune genes having similar amounts of episodic diversifying selection. Despite BRCA2’s status as a key caretaker gene, episodic diversifying selection was detected across mammals. The site‑specific selection analyses revealed that the two apoptosis associated domains of the Casp8 gene of bats (Chiroptera) are under opposing forces of selection (positive and negative respectively), highlighting the importance of site‑specific selection analyses to understand the evolution of highly complex gene families. Our results highlighted the need to critically assess different types of selection pressure on cancer associated genes when investigating evolutionary adaptations to cancer across the tree of life. This study provides an extensive assessment of cancer associated genes in mammals with highly representative, and substantially large sample size for a comparative genomic analysis in the field and identifies various avenues for future research into the mechanisms of cancer resistance and susceptibility in mammals.  \nKeywords Cancer susceptibility, Comparative genomics, Mammals, Bioinformatics, Evolution, HyPhy  \nAlthough many multicellular organisms face the threat of cancer1, differences in environment, life history traits and behaviour can influence an organism’s propensity for cancer risk2. In theory, those that are particularly susceptible to neoplasm should have evolved better resistance to cancer3. For example, it would be expected that long-lived, larger bodied species, would have a higher risk of cancer due to increased cell division4. However, large animals like the bowhead whale (Balaena mysticetus), and relatively long-lived animals like the naked mole rat (Heterocephalus glaber) exhibit fewer incidences of cancer5,6. This disparity has been coined as Peto’s paradox7,8. Several studies8–11 have addressed Peto’s paradox, finding that increases in body size and life span are accompanied by adaptations to reduce cancer risk. In captive animals, cancer mortality risk is largely independent of both body mass and adult life expectancy across species12, while the main risk factors are environmental, particularly diet. Carnivorous mammals have been found to have the highest cancer related mortality risk compared to the least cancer-prone mammalian order, Artiodactyla (even-toed ungulates)12.  \nLong-lived and large species have evolved a plethora of anticancer defences and strategies to supres","cbCaisxjlcPD27hO","https://ap.wps.com/l/cbCaisxjlcPD27hO","pdf",3729001,14,"English","# Introduction\n## Background and motivation (Peto’s paradox, cancer risk variation)\n## Gene categories and study aim\n# Methods\n## Taxon sampling and comparative genomic framework\n## Phylogenetic and selection analyses\n# Results\n## Gene-wide patterns across mammals\n## Site-specific selection in Casp8 (bats)\n# Discussion and implications\n## Need to evaluate selection pressure types\n## Future research directions","[{\"question\":\"What gene categories are analyzed in this study?\",\"answer\":\"The study analyzes oncogenes, tumour suppressor genes, and immune genes, including specific examples such as GRB2, FGL2, CDC42, LITAF, Casp8, BRCA2, IL2, CD274, and B2M.\"},{\"question\":\"Do cancer-associated genes generally evolve alongside species evolution?\",\"answer\":\"Phylogenetic results indicate that, for most species, the evolution of cancer-associated genes follows the species’ evolutionary history.\"},{\"question\":\"What was found about Casp8 selection in bats?\",\"answer\":\"Site-specific selection analyses show that the two apoptosis-associated domains of the Casp8 gene in bats are under opposing selection forces, with positive selection on one domain and negative selection on the other.\"}]","The molecular evolution of cancer associated genes in mammals | PDF",1789996657,35]