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Progressive Loss of Function in a Limb Enhancer during Snake Evolution.

Cell | 2016

The evolution of body shape is thought to be tightly coupled to changes in regulatory sequences, but specific molecular events associated with major morphological transitions in vertebrates have remained elusive. We identified snake-specific sequence changes within an otherwise highly conserved long-range limb enhancer of Sonic hedgehog (Shh). Transgenic mouse reporter assays revealed that the in vivo activity pattern of the enhancer is conserved across a wide range of vertebrates, including fish, but not in snakes. Genomic substitution of the mouse enhancer with its human or fish ortholog results in normal limb development. In contrast, replacement with snake orthologs caused severe limb reduction. Synthetic restoration of a single transcription factor binding site lost in the snake lineage reinstated full in vivo function to the snake enhancer. Our results demonstrate changes in a regulatory sequence associated with a major body plan transition and highlight the role of enhancers in morphological evolution. PAPERCLIP.

Pubmed ID: 27768887 RIS Download

Associated grants

  • Agency: NHGRI NIH HHS, United States
    Id: R01 HG003988
  • Agency: NIDCR NIH HHS, United States
    Id: U01 DE024427
  • Agency: NHGRI NIH HHS, United States
    Id: U54 HG006997

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Charles River Laboratories (tool)

RRID:SCR_003792

Commercial organism provider selling mice, rats and other model animals. American corporation specializing in a variety of pre-clinical and clinical laboratory services for the pharmaceutical, medical device and biotechnology industries. It also supplies assorted biomedical products and research and development outsourcing services for use in the pharmaceutical industry. (Wikipedia)

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GigaDB (tool)

RRID:SCR_004002

Repository to host data and tools associated with articles in GigaScience; however, it also includes a subset of datasets that are not associated with GigaScience articles. GigaDB defines a dataset as a group of files (e.g., sequencing data, analyses, imaging files, software programs) that are related to and support an article or study. Through their association with DataCite, each dataset will be assigned a DOI that can be used as a standard citation for future use of these data in other articles by the authors and other researchers. Datasets in GigaDB all require a title that is specific to the dataset, an author list, and an abstract that provides information specific to the data included within the set. Detailed information about the data to be submitted is encouraged in ISA-Tab, a format used by the BioSharing and ISA Commons communities that they work with to maintain the highest data and metadata standards in their journal.

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VISTA Enhancer Browser (tool)

RRID:SCR_007973

Resource for experimentally validated human and mouse noncoding fragments with gene enhancer activity as assessed in transgenic mice. Most of these noncoding elements were selected for testing based on their extreme conservation in other vertebrates or epigenomic evidence (ChIP-Seq) of putative enhancer marks. Central public database of experimentally validated human and mouse noncoding fragments with gene enhancer activity as assessed in transgenic mice. Users can retrieve elements near single genes of interest, search for enhancers that target reporter gene expression to particular tissue, or download entire collections of enhancers with defined tissue specificity or conservation depth.

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Gblocks (tool)

RRID:SCR_015945

Software that eliminates poorly aligned positions and divergent regions of a DNA or protein alignment so that it becomes more suitable for phylogenetic analysis.

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PhyML (web application)

RRID:SCR_014629

Web phylogeny server based on the maximum-likelihood principle.

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MAFFT (software resource)

RRID:SCR_011811

Software package as multiple alignment program for amino acid or nucleotide sequences. Can align up to 500 sequences or maximum file size of 1 MB. First version of MAFFT used algorithm based on progressive alignment, in which sequences were clustered with help of Fast Fourier Transform. Subsequent versions have added other algorithms and modes of operation, including options for faster alignment of large numbers of sequences, higher accuracy alignments, alignment of non-coding RNA sequences, and addition of new sequences to existing alignments.

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PhyML (web application)

RRID:SCR_014629

Web phylogeny server based on the maximum-likelihood principle.

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MAFFT (software resource)

RRID:SCR_011811

Software package as multiple alignment program for amino acid or nucleotide sequences. Can align up to 500 sequences or maximum file size of 1 MB. First version of MAFFT used algorithm based on progressive alignment, in which sequences were clustered with help of Fast Fourier Transform. Subsequent versions have added other algorithms and modes of operation, including options for faster alignment of large numbers of sequences, higher accuracy alignments, alignment of non-coding RNA sequences, and addition of new sequences to existing alignments.

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