Origin and stepwise evolution of vertebrate lungs.

Area of Science:

• Evolutionary biology
• Comparative genomics
• Developmental biology

Background:

• Lungs are vital respiratory organs in terrestrial vertebrates, with their presence in bony fish but absence in cartilaginous fish offering insights into organ evolution.
• Understanding lung evolution requires examining genetic and developmental similarities and differences across vertebrate species.

Purpose of the Study:

• To investigate the evolutionary origins and genetic underpinnings of lung development across vertebrates.
• To identify conserved and novel genetic elements contributing to lung formation and function.

Main Methods:

• Analysis of single-cell RNA sequencing data from adult and developing lungs across diverse vertebrate species.
• Comparative genomic analysis to identify conserved and novel genes and enhancers.
• Functional validation of key genes in model organisms (e.g., mice).

Main Results:

• Significant similarities in lung cell composition, developmental trajectories, and gene expression patterns were found across species.
• A substantial genetic foundation for lung development, including genes and enhancers, existed in the common ancestor of jawed vertebrates, even in species lacking lungs.
• Mammal-specific alveolar type 1 cells and genes like AGER and SFTA2 were identified, with SFTA2 deletion causing severe respiratory defects in mice.

Conclusions:

• Vertebrate lung evolution was shaped by both modifications in regulatory networks and the emergence of new genes.
• The genetic toolkit for lung development was largely established before the emergence of lungs, with subsequent innovations driving specialization.
• Specific genes, such as SFTA2, play critical roles in mammalian lung function, underscoring the importance of gene emergence in organ evolution.