Comparative genomics on Shisa orthologs

Area of Science:

• Molecular Biology
• Genomics
• Proteomics

Background:

• WNT and FGF signaling pathways are vital in development and implicated in human cancers like gastric and colorectal cancer.
• Xenopus shisa is known to inhibit WNT and FGF receptor maturation, suggesting a role in regulating these pathways.

Purpose of the Study:

• To identify and characterize the rat Shisa (Tmem46) gene.
• To analyze the molecular evolution and conservation of Shisa orthologs across different species.

Main Methods:

• Bioinformatics analyses including comparative proteomics and comparative genomics.
• Sequence analysis of the rat Shisa gene and its encoded protein.
• Comparison of Shisa orthologs from rat, mouse, human, chicken, Xenopus, and zebrafish.

Main Results:

• The rat Shisa gene (Tmem46) was identified and located on chromosome 15p12, encoding a type I transmembrane protein.
• High amino-acid identity was observed between rat Shisa and its mammalian orthologs (mouse, human).
• Conserved domains (extracellular Cys-rich, C-terminal cytoplasmic) were identified, though promoter regions showed less conservation, suggesting functional divergence.

Conclusions:

• This is the first report detailing the rat Shisa gene and its molecular evolution.
• Functional divergence of human SHISA from Xenopus shisa is predicted due to evolutionary changes in both protein and promoter regions.
• Understanding Shisa evolution provides insights into WNT and FGF pathway regulation in different species.