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Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints

The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones)...

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Autores principales: Irimia, Manuel, Tena, Juan J., Alexis, Maria S., Fernandez-Miñan, Ana, Maeso, Ignacio, Bogdanović, Ozren, de la Calle-Mustienes, Elisa, Roy, Scott W., Gómez-Skarmeta, José L., Fraser, Hunter B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514665/
https://www.ncbi.nlm.nih.gov/pubmed/22722344
http://dx.doi.org/10.1101/gr.139725.112
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author Irimia, Manuel
Tena, Juan J.
Alexis, Maria S.
Fernandez-Miñan, Ana
Maeso, Ignacio
Bogdanović, Ozren
de la Calle-Mustienes, Elisa
Roy, Scott W.
Gómez-Skarmeta, José L.
Fraser, Hunter B.
author_facet Irimia, Manuel
Tena, Juan J.
Alexis, Maria S.
Fernandez-Miñan, Ana
Maeso, Ignacio
Bogdanović, Ozren
de la Calle-Mustienes, Elisa
Roy, Scott W.
Gómez-Skarmeta, José L.
Fraser, Hunter B.
author_sort Irimia, Manuel
collection PubMed
description The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones). Here we report the first systematic survey of microsynteny conservation across metazoans, utilizing 17 genome sequences. We identified nearly 600 pairs of unrelated genes that have remained tightly physically linked in diverse lineages across over 600 million years of evolution. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results suggest that ancient genomic functional associations are far more common than previously thought—involving ∼12% of the ancestral bilaterian genome—and that cis-regulatory constraints are crucial in determining metazoan genome architecture.
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spelling pubmed-35146652013-06-01 Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints Irimia, Manuel Tena, Juan J. Alexis, Maria S. Fernandez-Miñan, Ana Maeso, Ignacio Bogdanović, Ozren de la Calle-Mustienes, Elisa Roy, Scott W. Gómez-Skarmeta, José L. Fraser, Hunter B. Genome Res Research The order of genes in eukaryotic genomes has generally been assumed to be neutral, since gene order is largely scrambled over evolutionary time. Only a handful of exceptional examples are known, typically involving deeply conserved clusters of tandemly duplicated genes (e.g., Hox genes and histones). Here we report the first systematic survey of microsynteny conservation across metazoans, utilizing 17 genome sequences. We identified nearly 600 pairs of unrelated genes that have remained tightly physically linked in diverse lineages across over 600 million years of evolution. Integrating sequence conservation, gene expression data, gene function, epigenetic marks, and other genomic features, we provide extensive evidence that many conserved ancient linkages involve (1) the coordinated transcription of neighboring genes, or (2) genomic regulatory blocks (GRBs) in which transcriptional enhancers controlling developmental genes are contained within nearby bystander genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos, which provided further evidence of putative GRBs in embryonic development. Finally, using chromosome conformation capture (3C) assays and stable transgenic experiments, we demonstrate that enhancers within bystander genes drive the expression of genes such as Otx and Islet, critical regulators of central nervous system development across bilaterians. These results suggest that ancient genomic functional associations are far more common than previously thought—involving ∼12% of the ancestral bilaterian genome—and that cis-regulatory constraints are crucial in determining metazoan genome architecture. Cold Spring Harbor Laboratory Press 2012-12 /pmc/articles/PMC3514665/ /pubmed/22722344 http://dx.doi.org/10.1101/gr.139725.112 Text en © 2012, Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research
Irimia, Manuel
Tena, Juan J.
Alexis, Maria S.
Fernandez-Miñan, Ana
Maeso, Ignacio
Bogdanović, Ozren
de la Calle-Mustienes, Elisa
Roy, Scott W.
Gómez-Skarmeta, José L.
Fraser, Hunter B.
Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints
title Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints
title_full Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints
title_fullStr Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints
title_full_unstemmed Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints
title_short Extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints
title_sort extensive conservation of ancient microsynteny across metazoans due to cis-regulatory constraints
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3514665/
https://www.ncbi.nlm.nih.gov/pubmed/22722344
http://dx.doi.org/10.1101/gr.139725.112
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