PUBLICATION

Evolution of Vertebrate Genes Related to Prion and Shadoo Proteins—Clues from Comparative Genomic Analysis

Authors
Premzl, M., Gready, J.E., Jermiin, L.S., Simonic, T., and0 Marshall Graves, J.A.
ID
ZDB-PUB-040908-13
Date
2004
Source
Mol. Biol. Evol.   21(12): 2210-2231 (Journal)
Registered Authors
Keywords
comparative genomics, conserved contiguity, phylogenetic analysis, repeats, regulatory sequences, phylogenetic footprinting
MeSH Terms
  • Animals
  • Base Sequence
  • Brain/metabolism
  • Computational Biology
  • Conserved Sequence/genetics
  • DNA Footprinting
  • DNA Primers
  • DNA Transposable Elements/genetics
  • Evolution, Molecular*
  • GPI-Linked Proteins
  • Gene Order
  • Genomics/methods
  • Humans
  • Likelihood Functions
  • Models, Genetic*
  • Molecular Sequence Data
  • Nerve Tissue Proteins/genetics*
  • Phylogeny*
  • Prions/genetics*
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Vertebrates/genetics*
PubMed
15342797 Full text @ Mol. Biol. Evol.
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping