PUBLICATION

Phylogenomic analysis of vertebrate thrombospondins reveals fish-specific paralogues, ancestral gene relationships and a tetrapod innovation

Authors
McKenzie, P., Chadalavada, S.C., Bohrer, J., and Adams, J.C.
ID
ZDB-PUB-060424-1
Date
2006
Source
BMC Evolutionary Biology   6(1): 33 (Journal)
Registered Authors
Keywords
none
MeSH Terms
  • Amino Acid Sequence
  • Animals
  • Chromosome Mapping
  • Computational Biology
  • Evolution, Molecular*
  • Fishes/genetics*
  • Humans
  • Phylogeny*
  • Sequence Homology, Amino Acid
  • Synteny
  • Thrombospondins/chemistry
  • Thrombospondins/genetics*
PubMed
16620379 Full text @ BMC Evol. Biol.
Abstract
ABSTRACT: BACKGROUND: Thrombospondins (TSPs) are evolutionarily-conserved, extracellular, calcium-binding glycoproteins with important roles in cell-extracellular matrix interactions, angiogenesis, synaptogenesis and connective tissue organisation. Five TSPs, designated TSP-1 through TSP-5, are encoded in the human genome. All but one have known roles in acquired or inherited human diseases. To further understand the roles of TSPs in human physiology and pathology, it would be advantageous to extend the repertoire of relevant vertebrate models. In general the zebrafish is proving an excellent model organism for vertebrate biology, therefore we set out to evaluate the status of TSPs in zebrafish and two species of pufferfish. RESULTS: We identified by bioinformatics that three fish species encode larger numbers of TSPs than vertebrates, yet all these sequences group as homologues of TSP-1 to -4. By phylogenomic analysis of neighboring genes, we uncovered that, in fish, a TSP-4-like sequence is encoded from the gene corresponding to the tetrapod TSP-5 gene. Thus, all TSP genes show conservation of synteny between fish and tetrapods. In the human genome, the TSP-1, TSP-3, TSP-4 and TSP-5 genes lie within paralogous regions that provide insight into the ancestral genomic context of vertebrate TSPs. CONCLUSIONS: A new model for TSP evolution in vertebrates is presented. The TSP-5 protein sequence has evolved rapidly from a TSP-4-like sequence as an innovation in the tetrapod lineage. TSP biology in fish is complicated by the presence of additional lineage- and species-specific TSP paralogues. These novel results give deeper insight into the evolution of TSPs in vertebrates and open new directions for understanding the physiological and pathological roles of TSP-4 and TSP-5 in humans.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping