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Cited by 146Genomics and Chromatin DynamicsChromosomal and Genetic VariationsGenome Rearrangement Algorithms

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

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Irimia, Manuel, Tena, Juan J., Alexis, Maria S., Fernandez-Miñan, Ana, Maeso, Ignacio, Bogdanović, Ozren, de la Calle-Mustienes, Elisa, Roy, Scott W. +2 more·2012·Genome Research
DOI 10.1101/gr.139725.112PMC PMC3514665
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Abstract

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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  • Many conserved local (subchromosomal) linkages of genes exist across many clades despite hundreds of millions of years of divergence.

    “many conserved local (subchromosomal) linkages of genes across many clades despite hundreds of millions of years of divergence”

    From Topological Approaches in Animal Comparative Genomics (2026) · cites this paper as [46]

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Authors
Irimia, M., Tena, J. J., Alexis, M. S., Fernandez-Miñan, A., Maeso, I., Bogdanović, O., de la Calle-Mustienes, E., Roy, S. W., Gómez-Skarmeta, J. L., & Fraser, H. B.
Affiliations
  • Stanford University (US)
  • Consejo Superior de Investigaciones Científicas (ES)
  • University of Oxford (GB)
Corresponding author
Irimia, Manuel
ORCID
Venue
Genome Research
Publisher
Cold Spring Harbor Laboratory
Published
2012-06-21
Volume
22
Issue
12
Pages
2356-2367
ISSN
1088-9051 (ISSN-L)
DOI
10.1101/gr.139725.112
PMC
PMC3514665
OpenAlex
W2113102609
Cited by
146
References
9
Citations by year
2026: 10 · 2025: 10 · 2024: 8 · 2023: 9 · 2022: 11 · 2021: 12 · 2020: 11 · 2019: 11 · 2018: 8 · 2017: 11 · 2016: 13 · 2015: 8 · 2014: 9 · 2013: 12 · 2012: 2
Type
posted content
Language
en
Open access
Locations
  • Genome Research (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • UWA Profiles and Research Repository (UWA) (submittedVersion, other-oa)
  • DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion, cc-by-nc)
Funders
  • National Institutes of Health (1r21hg005240-01a1)
  • National Human Genome Research Institute (1R21HG005240-01A1, R21 HG005240)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genome Rearrangement Algorithms
Keywords
microsynteny, gene order conservation, histone modifications, zebrafish embryonic development, Otx, islet, central nervous system development, bilaterian evolution, chromosome conformation capture
MeSH terms
Animals, Cell Line, Drosophila melanogaster, Enhancer Elements, Genetic, Genes, Homeobox, Humans, Zebrafish, Conserved Sequence, Caenorhabditis elegans, Gene Expression Regulation, Developmental, Evolution, Molecular, Gene Duplication, Gene Order, Genomics, Synteny, Microarray Analysis, Chromatin Immunoprecipitation, Genetic Association Studies

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