title: Structural evolution of Otx genes in craniates.
abstract: Using a degenerate PCR approach, we performed an exhaustive search of Otx genes in the reedfish Erpetoichthys calabaricus, the dogfish Scyliorhinus canicula, and the hagfish Myxine glutinosa. Three novel Otx genes were identified in each of these species, and their deduced protein sequences were determined over a large C-terminal fragment located immediately downstream of the homeodomain. Like their lamprey and osteichthyan counterparts, these nine genes display a tandem duplication of a 20--25-residue C-terminal domain, which appears to be a hallmark of all craniate Otx genes identified thus far, including the highly divergent Crx gene. Phylogenetic analyses show that, together with their osteichthyan counterparts, the dogfish and reedfish genes can be classified into three gnathostome orthology classes. Two of the three genes identified in each of these species belong to the Otx1 and Otx2 orthology classes previously characterized in osteichthyans. The third one unambiguously clusters with the Otx5/Otx5b genes recently characterized in Xenopus laevis, thus defining a novel orthology class. Our results also strongly suggest that the highly divergent Crx genes identified in humans, rodents, and oxen are the mammalian representatives of this third class. The hagfish genes display no clear relationships to the three gnathostome orthology classes, but one of them appears to be closely related to the LjOtxA gene, previously identified in Lampetra japonica. Taken together, these data support the hypothesis that the Otx multigene families characterized in craniates all derive from duplications of a single ancestral gene which occurred after the splitting of cephalochordates but prior to the gnathostome radiation. Using site-by-site sequence comparisons of the gnathostome Otx proteins, we also identified structural constraints selectively acting on each of the three gnathostome orthology classes. This suggests that specialized functions for each of these orthology classes were fixed in the gnathostome lineage prior to the splitting between osteichthyans and chondrichthyans.
authors.affiliation: Equipe ATIPE de l'UPRES-A 8080 Développement et Evolution, Orsay, France.
authors.forename: A
authors.initials: A
authors.lastname: Germot
authors.forename: G
authors.initials: G
authors.lastname: Lecointre
authors.forename: J L
authors.initials: JL
authors.lastname: Plouhinec
authors.forename: C
authors.initials: C
authors.lastname: Le Mentec
authors.forename: F
authors.initials: F
authors.lastname: Girardot
authors.forename: S
authors.initials: S
authors.lastname: Mazan
mesh_terms: D000818:Animals; D002816:Chordata, Nonvertebrate / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004284:Dogfish / Q000235:genetics; D019143:Evolution, Molecular; D005399:Fishes / Q000235:genetics*; D020440:Gene Duplication; D006196:Hagfishes / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics; D051857:Otx Transcription Factors; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors; D014714:Vertebrates / Q000235:genetics; D029961:Zebrafish Proteins
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D051857:Otx Transcription Factors; C413467:Otx5 protein, zebrafish; D015534:Trans-Activators; D014157:Transcription Factors; D029961:Zebrafish Proteins; D004247:DNA