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ZFIN ID: ZDB-PUB-041111-18
Identification of the mammalian Not gene via a phylogenomic approach
Plouhinec, J.L., Granier, C., Le Mentec, C., Lawson, K.A., Saberan-Djoneidi, D., Aghion, J., Shi, D.L., Collignon, J., and Mazan, S.
Date: 2004
Source: Gene expression patterns : GEP   5(1): 11-22 (Journal)
Registered Authors:
Keywords: Not; Floating head; Nodal; Foxa2; Axial mesoderm; Notochord; Node; Phylogenomic; Bayesian algorithm; NKL complex
MeSH Terms:
  • Amino Acid Sequence
  • Animals
  • Bayes Theorem
  • DNA-Binding Proteins/genetics*
  • DNA-Binding Proteins/metabolism
  • Homeodomain Proteins/genetics*
  • Homeodomain Proteins/metabolism
  • Humans
  • Mice
  • Molecular Sequence Data
  • Multigene Family
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • Phylogeny
  • Protein Structure, Secondary
  • Rats
  • Synteny
  • Transcription Factors/genetics*
  • Transcription Factors/metabolism
  • Xenopus
PubMed: 15533813 Full text @ Gene Expr. Patterns
Despite the great morphological diversity of early embryos, the underlying mechanisms of gastrulation are known to be broadly conserved in vertebrates. However, a number of genes characterized as fulfilling an essential function in this process in several model organisms display no clear ortholog in mammalian genomes. We have devised an in silico phylogenomic approach, based on exhaustive similarity searches in vertebrate genomes and subsequent bayesian phylogenetic analyses, to identify such missing genes, presumed to be highly divergent. This approach has been used to identify mammalian orthologs of Not, an homeodomain containing gene previously characterized in Xenopus, chick and zebrafish as playing a critical role in the formation of the notochord. This attempt led to the identification of a highly divergent mammalian Not-related gene in the mouse, human and rat. The results from phylogenetic reconstructions, synteny analyses, expression pattern analyses in wild-type and mutant mouse embryos, and overexpression experiments in Xenopus embryos converge to confirm these genes as representatives of the Not family in mammals. The identification of the mammalian Not gene delivers an important component for the understanding of the genetics underlying notochord formation in mammals and its evolution among vertebrates. The phylogenomic method used to retrieve this gene thus provides a tool, which can complement or validate genome annotations in situations when they are weakly supported.