MSc Thesis Defense: Abdulrahman Murad, A PHYLOGENETICALLY-STRUCTURED FRAMEWORK FOR IDENTIFYING RECEPTOR-SPECIFIC EVOLUTIONARY SIGNATURES: APPLICATION TO CLASS B GPCRS AND THE CELSR ADHESION GPCR FAMILY, Date & Time: 22 July, 2026 – 12:00 PM, Place: FENS L
A PHYLOGENETICALLY-STRUCTURED FRAMEWORK FOR
IDENTIFYING RECEPTOR-SPECIFIC EVOLUTIONARY
SIGNATURES: APPLICATION TO CLASS B GPCRS AND THE
CELSR ADHESION GPCR FAMILY
Abdulrahman Murad
Molecular Biology, Genetics and Bioengineering , MSc Thesis, 2026
Thesis Jury
Assoc. Prof. Ogün Adebali (Thesis Advisor)
Prof. Levent Öztürk
Assoc. Prof. Efe Sezgin
Date & Time: July22nd, 2026 – 12:00 PM
Place: FENS L029
Zoom: https://sabanciuniv.
Keywords : adhesion GPCRs, CELSR, functionally equivalent orthologs, receptor-specific conservation, molecular phylogenetics
Abstract
The three members of the CELSR adhesion GPCR family, CELSR1, CELSR2, and CELSR3, share a conserved multidomain architecture but perform distinct developmental roles. CELSR1 regulates epithelial planar cell polarity, CELSR2 promotes neuronal growth and ependymal ciliogenesis, and CELSR3 directs long-range axonal tract formation in the developing brain. Identifying the residues that encode these divergent functions requires separating receptor-specific evolutionary constraints from those shared across the family, since conventional conservation analyses merge orthologous and paralogous sequences and blur that distinction. This thesis uses a pairwise comparison framework based on functionally equivalent orthologs across the full Class B GPCR superfamily, identifying positions highly conserved within each receptor’s lineage but biochemically distinct in all other family members. Applied to the CELSR family, the receptor-specific residue distributions are nonoverlapping and closely match established biology. CELSR1 signal is enriched on the Laminin G-like 2 domain, the solvent-exposed face of its extracellular compact module, consistent with its role in epithelial planar cell polarity. CELSR3 signal is dominated by the cytoplasmic tail, consistent with its growth-suppressive function in axon guidance and neural circuit formation. The independent recovery of clinically validated and experimentally characterized residues confirms that the framework captures genuine functional constraint at residue-level resolution.