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Enhancer conservation
Enhancers tend to be conserved but less so than essential coding regions
Snake ZRS example
Snake-specific sequence changes in an otherwise conserved limb enhancer
ETS1 motif loss
Specific TF binding site lost in snakes prevents SHH limb expression
"Serpentized" mice
Mouse ZRS replaced with snake ZRS → limb reduction
Functional restoration
Restoring the single ETS1 motif rescues full enhancer function
Key insight
Single regulatory changes can drive major morphological transitions
Publication
Kvon et al., "Progressive Loss of Function in a Limb Enhancer during Snake Evolution"