Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer
Cetaceans are the longest-living species of mammals and the largest in the history of the planet. They have developed mechanisms against diseases such cancer, although the underlying molecular bases of these remain unknown. The goal of this study was to investigate the role of natural selection in t...
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crroyalsociety:10.1098/rspb.2020.2592 2024-09-09T19:31:48+00:00 Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer Tejada-Martinez, Daniela de Magalhães, João Pedro Opazo, Juan C. Biotechnology and Biological Sciences Research Council Fondo Nacional de Desarrollo Científico y Tecnológico Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) - Chile through the doctoral studentship 2021 http://dx.doi.org/10.1098/rspb.2020.2592 https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2020.2592 https://royalsocietypublishing.org/doi/full-xml/10.1098/rspb.2020.2592 en eng The Royal Society https://royalsociety.org/-/media/journals/author/Licence-to-Publish-20062019-final.pdf https://royalsociety.org/journals/ethics-policies/data-sharing-mining/ Proceedings of the Royal Society B: Biological Sciences volume 288, issue 1945, page 20202592 ISSN 0962-8452 1471-2954 journal-article 2021 crroyalsociety https://doi.org/10.1098/rspb.2020.2592 2024-08-26T04:21:00Z Cetaceans are the longest-living species of mammals and the largest in the history of the planet. They have developed mechanisms against diseases such cancer, although the underlying molecular bases of these remain unknown. The goal of this study was to investigate the role of natural selection in the evolution of 1077 tumour suppressor genes (TSGs) in cetaceans. We used a comparative genomic approach to analyse two sources of molecular variation in the form of d N / d S rates and gene copy number variation. We found a signal of positive selection in the ancestor of cetaceans within the CXCR2 gene, an important regulator of DNA damage, tumour dissemination and immune system. Further, in the ancestor of baleen whales, we found six genes exhibiting positive selection relating to diseases such as breast carcinoma, lung neoplasm ( ADAMTS8 ) and leukaemia ( ANXA1 ). The TSGs turnover rate (gene gain and loss) was almost 2.4-fold higher in cetaceans when compared with other mammals, and notably even faster in baleen whales. The molecular variants in TSGs found in baleen whales, combined with the faster gene turnover rate, could have favoured the evolution of their particular traits of anti-cancer resistance, gigantism and longevity. Additionally, we report 71 genes with duplications, of which 11 genes are linked to longevity (e.g. NOTCH3 and SIK1 ) and are important regulators of senescence, cell proliferation and metabolism. Overall, these results provide evolutionary evidence that natural selection in TSGs could act on species with large body sizes and extended lifespan, providing novel insights into the genetic basis of disease resistance. Article in Journal/Newspaper baleen whales The Royal Society Proceedings of the Royal Society B: Biological Sciences 288 1945 20202592 |
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English |
description |
Cetaceans are the longest-living species of mammals and the largest in the history of the planet. They have developed mechanisms against diseases such cancer, although the underlying molecular bases of these remain unknown. The goal of this study was to investigate the role of natural selection in the evolution of 1077 tumour suppressor genes (TSGs) in cetaceans. We used a comparative genomic approach to analyse two sources of molecular variation in the form of d N / d S rates and gene copy number variation. We found a signal of positive selection in the ancestor of cetaceans within the CXCR2 gene, an important regulator of DNA damage, tumour dissemination and immune system. Further, in the ancestor of baleen whales, we found six genes exhibiting positive selection relating to diseases such as breast carcinoma, lung neoplasm ( ADAMTS8 ) and leukaemia ( ANXA1 ). The TSGs turnover rate (gene gain and loss) was almost 2.4-fold higher in cetaceans when compared with other mammals, and notably even faster in baleen whales. The molecular variants in TSGs found in baleen whales, combined with the faster gene turnover rate, could have favoured the evolution of their particular traits of anti-cancer resistance, gigantism and longevity. Additionally, we report 71 genes with duplications, of which 11 genes are linked to longevity (e.g. NOTCH3 and SIK1 ) and are important regulators of senescence, cell proliferation and metabolism. Overall, these results provide evolutionary evidence that natural selection in TSGs could act on species with large body sizes and extended lifespan, providing novel insights into the genetic basis of disease resistance. |
author2 |
Biotechnology and Biological Sciences Research Council Fondo Nacional de Desarrollo Científico y Tecnológico Comisión Nacional de Investigación Científica y Tecnológica (CONICYT) - Chile through the doctoral studentship |
format |
Article in Journal/Newspaper |
author |
Tejada-Martinez, Daniela de Magalhães, João Pedro Opazo, Juan C. |
spellingShingle |
Tejada-Martinez, Daniela de Magalhães, João Pedro Opazo, Juan C. Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer |
author_facet |
Tejada-Martinez, Daniela de Magalhães, João Pedro Opazo, Juan C. |
author_sort |
Tejada-Martinez, Daniela |
title |
Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer |
title_short |
Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer |
title_full |
Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer |
title_fullStr |
Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer |
title_full_unstemmed |
Positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer |
title_sort |
positive selection and gene duplications in tumour suppressor genes reveal clues about how cetaceans resist cancer |
publisher |
The Royal Society |
publishDate |
2021 |
url |
http://dx.doi.org/10.1098/rspb.2020.2592 https://royalsocietypublishing.org/doi/pdf/10.1098/rspb.2020.2592 https://royalsocietypublishing.org/doi/full-xml/10.1098/rspb.2020.2592 |
genre |
baleen whales |
genre_facet |
baleen whales |
op_source |
Proceedings of the Royal Society B: Biological Sciences volume 288, issue 1945, page 20202592 ISSN 0962-8452 1471-2954 |
op_rights |
https://royalsociety.org/-/media/journals/author/Licence-to-Publish-20062019-final.pdf https://royalsociety.org/journals/ethics-policies/data-sharing-mining/ |
op_doi |
https://doi.org/10.1098/rspb.2020.2592 |
container_title |
Proceedings of the Royal Society B: Biological Sciences |
container_volume |
288 |
container_issue |
1945 |
container_start_page |
20202592 |
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1809900619163500544 |