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Updated: Jul 28, 2025

A Rapid In Vivo Bioassay for Developmentally Active Enhancers
Developmental regulation of conserved non-coding element evolution provides insights into limb loss in squamates
Zeng Wang1,2, Changjun Peng1,2, Wei Wu1,2
1CAS Key Laboratory of Mountain Ecological Restoration and Bioresource Utilization & h Ecological Restoration and Biodiversity Conservation Key Laboratory of Sichuan Province, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, 610041, China.
Conserved non-coding elements (CNEs) show significant changes, including insertions and deletions (InDels), in limbless lizards. These genetic alterations impact genes crucial for limb development, explaining limb loss evolution in reptiles.
Area of Science:
- Evolutionary biology
- Developmental genetics
- Genomics
Background:
- Limb loss is a recurring evolutionary event in squamate reptiles.
- Understanding the genetic mechanisms driving limb loss is crucial for evolutionary studies.
Purpose of the Study:
- Investigate the role of conserved non-coding elements (CNEs) in limb development and loss.
- Identify genetic changes in CNEs associated with limb reduction in different lizard lineages.
Main Methods:
- De novo genome assembly of three limbless lizard species.
- Analysis of conserved non-coding elements (CNEs) and their associated genes.
- Functional experiments to assess the impact of mutations and insertions/deletions (InDels) on CNE regulatory function.
Main Results:
- Divergence in CNEs associated with limb initiation and outgrowth genes was observed.
- Extensive lineage-specific insertions and deletions (InDels) were found in CNEs of limbless squamates.
- Mutations and InDels in CNEs were shown to alter gene regulatory functions, affecting key limb development genes like Tbx4, Fgf10, and Gli3.
Conclusions:
- Conserved non-coding elements (CNEs) and their regulatory variations, particularly InDels, are key molecular drivers of limb loss in squamate reptiles.
- This study provides developmental insights into the evolution of limblessness.
- Regulatory element InDels play a significant role in phenotypic evolution across species.
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