title: Phylogenetic analyses uncover a novel clade of transferrin in nonmammalian vertebrates.
abstract: Transferrin is a protein super-family involved in iron transport, a central process in cellular homeostasis. Throughout the evolution of vertebrates, transferrin members have diversified into distinct subfamilies including serotransferrin, ovotransferrin, lactoferrin, melanotransferrin, the inhibitor of carbonic anhydrase, pacifastin, and the major yolk protein in sea urchin. Previous phylogenetic analyses have established the branching order of the diverse transferrin subfamilies but were mostly focused on the transferrin repertoire present in mammals. Here, we conduct a comprehensive phylogenetic analysis of transferrin protein sequences in sequenced vertebrates, placing a special focus on the less-studied nonmammalian vertebrates. Our analyses uncover a novel transferrin clade present across fish, sauropsid, and amphibian genomes but strikingly absent from mammals. Our reconstructed scenario implies that this novel class emerged through a duplication event at the vertebrate ancestor, and that it was subsequently lost in the lineage leading to mammals. We detect footprints of accelerated evolution following the duplication event, which suggest positive selection and early functional divergence of this novel clade. Interestingly, the loss of this novel class of transferrin in mammals coincided with the divergence by duplication of lactoferrin and serotransferrin in this lineage. Altogether, our results provide novel insights on the evolution of iron-binding proteins in the various vertebrate groups.
authors.affiliation: School of Biosciences & Biotechnology, Faculty of Science Technology, Universiti Kebangsaan Malaysia, Selangor, Malaysia.
authors.forename: Hirzahida
authors.initials: H
authors.lastname: Mohd-Padil
authors.forename: Adura
authors.initials: A
authors.lastname: Mohd-Adnan
authors.forename: Toni
authors.initials: T
authors.lastname: Gabaldón
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001492:Bass / Q000235:genetics*; D001499:Bayes Theorem; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D029941:Fish Proteins / Q000737:chemistry / Q000235:genetics*; D020440:Gene Duplication; D016013:Likelihood Functions; D008957:Models, Genetic; D008958:Models, Molecular; D005810:Multigene Family; D010802:Phylogeny; D017433:Protein Structure, Secondary; D012641:Selection, Genetic; D040681:Structural Homology, Protein; D014168:Transferrin / Q000737:chemistry / Q000235:genetics*; D014714:Vertebrates / Q000235:genetics
chemical_list: D029941:Fish Proteins; D014168:Transferrin