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Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility

Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore...

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Autores principales: Lu, Yuan, Sandoval, Angel, Voss, Sarah, Lai, Zhao, Kneitz, Susanne, Boswell, Will, Boswell, Mikki, Savage, Markita, Walter, Christi, Warren, Wes, Schartl, Manfred, Walter, Ronald
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703647/
https://www.ncbi.nlm.nih.gov/pubmed/33168740
http://dx.doi.org/10.1073/pnas.2010133117
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author Lu, Yuan
Sandoval, Angel
Voss, Sarah
Lai, Zhao
Kneitz, Susanne
Boswell, Will
Boswell, Mikki
Savage, Markita
Walter, Christi
Warren, Wes
Schartl, Manfred
Walter, Ronald
author_facet Lu, Yuan
Sandoval, Angel
Voss, Sarah
Lai, Zhao
Kneitz, Susanne
Boswell, Will
Boswell, Mikki
Savage, Markita
Walter, Christi
Warren, Wes
Schartl, Manfred
Walter, Ronald
author_sort Lu, Yuan
collection PubMed
description Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore named as hybrid incompatibility. Interspecies hybridization between southern platyfish and green swordtails leads to lethal melanocyte tumorigenesis. This occurs in hybrids with tumor incidence following progeny ratio that is consistent with two-locus interaction, suggesting melanoma development is a result of negative epistasis. Such observations make Xiphophorus one of the only two vertebrate hybrid incompatibility examples in which interacting genes have been identified. One of the two interacting loci has been characterized as a mutant epidermal growth factor receptor. However, the other locus has not been identified despite over five decades of active research. Here we report the localization of the melanoma regulatory locus to a single gene, rab3d, which shows all expected features of the long-sought oncogene interacting locus. Our findings provide insights into the role of egfr regulation in regard to cancer etiology. Finally, they provide a molecular explainable example of hybrid incompatibility.
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spelling pubmed-77036472020-12-10 Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility Lu, Yuan Sandoval, Angel Voss, Sarah Lai, Zhao Kneitz, Susanne Boswell, Will Boswell, Mikki Savage, Markita Walter, Christi Warren, Wes Schartl, Manfred Walter, Ronald Proc Natl Acad Sci U S A Biological Sciences Mixing genomes of different species by hybridization can disrupt species-specific genetic interactions that were adapted and fixed within each species population. Such disruption can predispose the hybrids to abnormalities and disease that decrease the overall fitness of the hybrids and is therefore named as hybrid incompatibility. Interspecies hybridization between southern platyfish and green swordtails leads to lethal melanocyte tumorigenesis. This occurs in hybrids with tumor incidence following progeny ratio that is consistent with two-locus interaction, suggesting melanoma development is a result of negative epistasis. Such observations make Xiphophorus one of the only two vertebrate hybrid incompatibility examples in which interacting genes have been identified. One of the two interacting loci has been characterized as a mutant epidermal growth factor receptor. However, the other locus has not been identified despite over five decades of active research. Here we report the localization of the melanoma regulatory locus to a single gene, rab3d, which shows all expected features of the long-sought oncogene interacting locus. Our findings provide insights into the role of egfr regulation in regard to cancer etiology. Finally, they provide a molecular explainable example of hybrid incompatibility. National Academy of Sciences 2020-11-24 2020-11-09 /pmc/articles/PMC7703647/ /pubmed/33168740 http://dx.doi.org/10.1073/pnas.2010133117 Text en Copyright © 2020 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Biological Sciences
Lu, Yuan
Sandoval, Angel
Voss, Sarah
Lai, Zhao
Kneitz, Susanne
Boswell, Will
Boswell, Mikki
Savage, Markita
Walter, Christi
Warren, Wes
Schartl, Manfred
Walter, Ronald
Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility
title Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility
title_full Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility
title_fullStr Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility
title_full_unstemmed Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility
title_short Oncogenic allelic interaction in Xiphophorus highlights hybrid incompatibility
title_sort oncogenic allelic interaction in xiphophorus highlights hybrid incompatibility
topic Biological Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703647/
https://www.ncbi.nlm.nih.gov/pubmed/33168740
http://dx.doi.org/10.1073/pnas.2010133117
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