BMP7 peripheral sequence evolution correlates with mammalian cloacal septation.

Area of Science:

• Evolutionary Biology
• Molecular Biology
• Developmental Biology

Background:

• The transition from a single cloaca to separate urogenital and anal openings is a key event in vertebrate evolution.
• Understanding the molecular mechanisms underlying cloacal septation is crucial for insights into reproductive diversification and congenital anorectal malformations.

Purpose of the Study:

• To investigate the evolutionary changes in Bone Morphogenetic Protein 7 (BMP7), a key regulator of cloacal formation, across diverse vertebrate species.
• To identify molecular adaptations in BMP7 associated with the evolution of cloacal septation.

Main Methods:

• Phylogenetic analysis, sequence alignment, physicochemical assessment, domain analysis, motif analysis, and molecular docking were employed.
• BMP7 sequences from 37 vertebrate species, ranging from cartilaginous fish to mammals, were analyzed.
• Specific focus on conserved and divergent regions, isoelectric point shifts, and predicted regulatory interactions.

Main Results:

• The core TGF-beta domain of BMP7 exhibited high conservation (>90% identity) across vertebrates.
• Peripheral regions of BMP7 showed significant habitat-associated divergence, with altered isoelectric points and stability indices between aquatic and terrestrial species.
• Placental mammals displayed lineage-specific amino acid changes in BMP7, potentially refining regulation with FOXA1, and conserved motifs (GWQDWI) were identified in mammals and birds, contrasting with amphibian-reptile divergence (RACGCH).

Conclusions:

• Peripheral BMP7 regions have undergone adaptive evolution correlating with the transition from a cloaca to separate openings.
• Specific molecular changes in BMP7, particularly in placental mammals, are linked to the refined septation process.
• These findings provide molecular insights into the evolutionary pathways of vertebrate urogenital and anorectal development.