MBE Advance Access published online on September 1, 2004
Molecular Biology and Evolution, doi:10.1093/molbev/msh245
Molecular Biology and Evolution © Society for Molecular Biology and Evolution 2004; all rights reserved
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1 Computational Proteomics Group, John Curtin School of Medical Research, Australian National University, PO Box 334, Canberra ACT 2601 Australia
* To whom correspondence should be addressed. E-mail: Jill.Gready{at}anu.edu.au.
Recent findings of new genes in fish related to the prion protein (PrP) gene PRNP, including our recent report of SPRN coding for Shadoo (Sho) protein found also in mammals, raise issues of their function and evolution. Here we report additional novel fish genes found in public databases, including a duplicated SPRN gene, SPRNB, in Fugu, Tetraodon, carp, and zebrafish encoding the Sho2 protein, and use comparative genomic analysis to analyse the evolutionary relationships and to infer evolutionary trajectories of the complete data set. Phylogenetic footprinting performed on aligned human, mouse, and Fugu SPRN genes to define candidate regulatory promoter regions, detected 16 conserved motifs, 3 of which are known transcription-factor-binding sites for a receptor and transcription factors specific to or associated with expression in brain. This result and other homology-based (VISTA global genomic alignment; protein sequence alignment and phylogenetics) and context-dependent (genomic context; relative gene order and orientation) criteria indicate fish and mammalian SPRN genes are orthologous, and suggest a strongly conserved basic function in brain. Whereas tetrapod PRNPs share context with the analogous stPrP-2 coding gene in fish, their sequences are diverged, suggesting that the tetrapod and fish genes are likely to have significantly different functions. Phylogenetic analysis predicts the SPRN/SPRNB duplication occurred before divergence of fish from tetrapods, while that of stPrP-1 and stPrP-2 occurred in fish. Whereas Sho appears to have a conserved function in vertebrate brain, PrP seems to have an adaptive role fine-tuned in a lineage-specific fashion. An evolutionary model consistent with our findings and literature knowledge is proposed which has an ancestral pre-vertebrate SPRN-like gene leading to all vertebrate PrP- and Sho-related genes. This provides a new framework for exploring the evolution of this unusual family of proteins, and for searching for members in other fish branches and intermediate vertebrate groups.
Research Article
Evolution of vertebrate genes related to Prion and Shadoo proteins - clues from comparative genomic analysis
2 School of Biological Sciences and Biological Informatics & Technology Centre, University of Sydney NSW 2006 Australia
3 Dipartimento di Patologia Animale, Igiene e Sanità Pubblica Veterinaria, Sezione di Biochimica e Fisiologia Veterinaria, Università di Milano, via Celoria 10, 20133 Milan, Italy
4 Comparative Genomics Group, Research School of Biological Sciences, Australian National University, PO Box 475, Canberra ACT 2601 Australia
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