title: Phylogenetic analysis of eukaryotic NEET proteins uncovers a link between a key gene duplication event and the evolution of vertebrates.
abstract: NEET proteins belong to a unique family of iron-sulfur proteins in which the 2Fe-2S cluster is coordinated by a CDGSH domain that is followed by the "NEET" motif. They are involved in the regulation of iron and reactive oxygen metabolism, and have been associated with the progression of diabetes, cancer, aging and neurodegenerative diseases. Despite their important biological functions, the evolution and diversification of eukaryotic NEET proteins are largely unknown. Here we used the three members of the human NEET protein family (CISD1, mitoNEET; CISD2, NAF-1 or Miner 1; and CISD3, Miner2) as our guides to conduct a phylogenetic analysis of eukaryotic NEET proteins and their evolution. Our findings identified the slime mold Dictyostelium discoideum's CISD proteins as the closest to the ancient archetype of eukaryotic NEET proteins. We further identified CISD3 homologs in fungi that were previously reported not to contain any NEET proteins, and revealed that plants lack homolog(s) of CISD3. Furthermore, our study suggests that the mammalian NEET proteins, mitoNEET (CISD1) and NAF-1 (CISD2), emerged via gene duplication around the origin of vertebrates. Our findings provide new insights into the classification and expansion of the NEET protein family, as well as offer clues to the diverged functions of the human mitoNEET and NAF-1 proteins.
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton TX 76203, USA.
authors.forename: Madhuri A
authors.initials: MA
authors.lastname: Inupakutika
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton TX 76203, USA.
authors.forename: Soham
authors.initials: S
authors.lastname: Sengupta
authors.affiliation: The Alexander Silberman Institute of Life Science, Hebrew University of Jerusalem, Edmond J. Safra Campus at Givat Ram, Jerusalem 91904, Israel.
authors.forename: Rachel
authors.initials: R
authors.lastname: Nechushtai
authors.affiliation: Department of Chemistry &Biochemistry, University of California at San Diego, La Jolla, CA 92093, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Jennings
authors.affiliation: Center for Theoretical Biological Physics and Department of Physics and Astronomy, Chemistry and Biosciences, 239 Brockman Hall, 6100 Main Street- MS-61, Rice University, Houston, TX 77005, USA.
authors.forename: Jose' N
authors.initials: JN
authors.lastname: Onuchic
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton TX 76203, USA.|Department of Mathematics, University of North Texas, Denton, TX 76203, USA.
authors.forename: Rajeev K
authors.initials: RK
authors.lastname: Azad
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton TX 76203, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Padilla
authors.affiliation: Department of Biological Sciences, University of North Texas, Denton TX 76203, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Mittler
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D056890:Eukaryota / Q000235:genetics*; D019143:Evolution, Molecular; D020440:Gene Duplication; D006801:Humans; D007506:Iron-Sulfur Proteins / Q000737:chemistry / Q000235:genetics*; D010802:Phylogeny; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D014714:Vertebrates / Q000235:genetics
chemical_list: D007506:Iron-Sulfur Proteins