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Extensive conservation of ancient microsynteny across metazoans


ABSTRACT: Gene order, or microsynteny, is generally thought not to be conserved across metazoan phyla. Only a handful of exceptions, typically of tandemly duplicated genes such as Hox genes, have been discovered. Here, we performed a systematic survey for microsynteny conservation in 17 genomes and identified nearly 600 pairs of unrelated genes that have remained together across over 600 million years of evolution. Using multiple genome-wide resources, including several genomic features, epigenetic marks, sequence conservation and microarray expression data, we provide extensive evidence that many of these ancient microsyntenic arrangements have been conserved in order to preserve either (i) the coordinated transcription of neighboring genes, or (ii) Genomic Regulatory Blocks (GRBs), in which transcriptional enhancers controlling key developmental genes are contained within nearby “bystander” genes. In addition, we generated ChIP-seq data for key histone modifications in zebrafish embryos to further investigate 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 show that ancient genomic associations are far more common in modern metazoans than previously thought – likely involving over 12% of the ancestral bilaterian genome – and that cis-regulatory constraints have played a major role in conserving the architecture of metazoan genomes. ChIP-seq H3K27me3 of 24hpf zebrafish embryos

ORGANISM(S): Danio rerio

SUBMITTER: Ozren Bogdanovic 

PROVIDER: E-GEOD-35050 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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

Irimia Manuel M   Tena Juan J JJ   Alexis Maria S MS   Fernandez-Miñan Ana A   Maeso Ignacio I   Bogdanovic Ozren O   de la Calle-Mustienes Elisa E   Roy Scott W SW   Gómez-Skarmeta José L JL   Fraser Hunter B HB  

Genome research 20120621 12


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  ...[more]

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