By reusing old genes, bats became the only mammals able to fly

Basics

• Mammalian limb structure: All mammals share a common five-digit limb blueprint (pentadactyl limb).
• Bats’ uniqueness: Only mammals capable of true powered flight, achieved via wings.
• Wing formation: Forelimbs elongate digits 2–5; thin skin sheet called chiropatagium stretches between them.

Relevance :

• GS3 – Science & Technology / Biotechnology
  • Evolutionary biology, genetics, regulatory evolution.
  • Developmental biology insights applicable to medicine (congenital limb disorders, syndactyly).
  • Comparative genomics and single-cell analysis techniques.

Scientific Question

• How do bats develop wings while sharing the same genes as other mammals?
• Early embryos of bats, mice, dolphins, etc., look almost identical.
• Key concept: Regulatory evolution — altering when, where, and how genes are activated, rather than changing gene sequences.

Chiropatagium Mystery

• Traditionally, mammals lose skin between fingers via apoptosis (programmed cell death).
• Hypothesis: Bats suppressed interdigital apoptosis → wing formation.
• New study challenges this: apoptosis still occurs in bat wing tissue; something else must sustain the chiropatagium.

Study Approach

• Species used: Bats (Carollia perspicillata) and mice.
• Methodology:
  • Single-cell RNA sequencing of >180,000 embryonic limb cells.
  • Created an interspecies limb atlas for developmental comparison.
  • Computational modelling to identify cell types and gene activity.

Key Findings

1. Cell-level similarity: Bat and mouse limbs have almost identical cell types; no novel cell type was invented.
2. Specialized fibroblasts:
   1. A population of connective tissue cells (fibroblasts) is repositioned between digits in bats.
   2. These fibroblasts express transcription factors MEIS2 and TBX3, switched off in other mammals at this stage.
3. Evolutionary co-option:
   1. Existing gene programs redeployed in a new context → new structures without new genes.
4. Functional validation in mice:
   1. Transgenic mice expressing bat MEIS2 and TBX3 in distal limbs → fused, webbed digits resembling early bat wings.
   2. Shows regulatory changes alone can drive structural innovation.

Mechanistic Insights

• Regulatory shifts: Key to bat wing evolution; small changes in gene timing/location produce dramatic morphological differences.
• Apoptosis still occurs: Wing webbing persists due to specialized fibroblasts, not apoptosis suppression.
• Transcription factors as “genetic dials”: MEIS2 and TBX3 are sufficient to partially activate wing-building programs.

Broader Implications

• Evolutionary biology:
  • Supports the concept that diverse limb morphologies (bat wings, bird wings, whale flippers, fish fins) arise from modifying universal developmental blueprints.
• Developmental biology & medicine:
  • May inform understanding of syndactyly (fused digits in humans).
  • Insights into gene regulation during limb formation could aid diagnosis and treatment of congenital limb disorders.
• Research tools: Single-cell RNA sequencing and cross-species analysis enable mapping of regulatory changes driving evolution.

Takeaways

• Bat wings evolved through regulatory evolution, not new genes.
• Existing cell types were repurposed and strategically deployed.
• Small genetic shifts can yield major morphological innovations.
• Study demonstrates the power of transcription factors in shaping limbs across species.
• Highlights the potential of comparative genomics and single-cell analysis in unraveling evolutionary mechanisms.

---