ArticleCell2016
Progressive Loss of Function in a Limb Enhancer during Snake Evolution.
Article in Cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 199 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
199 citing papers in PubMed, 368 citations in OpenAlex.
- Loss, persistence and reversal of phenotypic traits.Biological reviews of the Cambridge Philosophical Society · 2026Review
- The gene-regulatory evolution of the human skeleton.Nature · 2026Article
- Synthetic Approaches as Empirical Tools for Testing Evolutionary Theory.Genome biology and evolution · 2026Review
- A putativebioRxiv : the preprint server for biology · 2026Article
- The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional convergence of regulatory regions provides vital insights into mammalian gliding adaptation.Science China. Life sciences · 2026Article
- Comparative analysis of conserved non-coding elements identifies gene regulatory networks rewired during the water-to-land transition in vertebrates.Biologia futura · 2026Article
- Comparative Genomic Screening Identifies Developmental Constraint Loci Underscoring the Phenotypic Evolution of Syngnathids.Integrative zoology · 2026Article
- Article
- The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.bioRxiv : the preprint server for biology · 2026Article
- Rewiring of two conserved signalling hubs into one axis underlies convergent female-specific wing regression in insects.Nature ecology & evolution · 2026Article
- The wide gape of snakes: A comparison of the developing mandibular symphysis in sauropsids.Journal of anatomy · 2026Article
- Genomic approaches for understanding the evolution of the human brain.Nature neuroscience · 2026Review
- Multi-scale dissection, compaction and derivatization of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Retracing and rewriting the evolutionary trajectories of mammalian developmental enhancers.bioRxiv : the preprint server for biology · 2026Article
- Distinct mechanisms decommission redundant enhancers to facilitate phenotypic evolution.Science advances · 2026Article
- The bacteria of a fig community.Microbiology spectrum · 2026Article
- Phenotypic complexity determines the predictability of molecular convergence.bioRxiv : the preprint server for biology · 2026Article
- Profiling the epigenomic landscape of late embryonic and adult mouse hind limb muscles.Scientific reports · 2026Article
- Article
139 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
19 authors at 4 institutions in 2 countries.
Funding
Abstract
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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.