Evolutionary studies on the HFE gene

• Type: Article in International Scientific Journal
• Date: 2001

Authors

rodrigues, p (Author) Other; berkeveld, m (Author) Other; porto, g (Author) ICBAS; salter-cid, l (Author) Other; de sousa, m (Author) Other

Journal

Title: European Journal of Immunogenetics

Vol. 28

Pages: 272-272

ISSN: 0960-7420

Publisher: Blackwell

Indexing

ISI Web of Knowledge

Scopus - 0 Citations

Other information

Authenticus ID: P-007-G93

Abstract (EN): HFE is glycoprotein homologous to MHC class-I molecules which associate with ß2m. The HFE molecule plays a role in iron metabolism, it binds to the transferrin receptor, and has been found in the liver, gut and other tissues. The HFE transcript of approximately 4 kb contains a 1029 nucleotide open reading frame encoding a polypeptide of 343 residues. The HFE sequence includes a hydrophobic leader followed by three extracellular domains (¿1, ¿2 and ¿3) and finally transmembrane and cytoplasmic sequences. Characterization of the mouse HFE have shown that it shares several features with the human HFE, having an overall amino acid sequence similarity of 66% and a similar expression pattern. In the present study we aimed to define the genomic structure and sequence of primate HFE and to collect evidence on the extent of the HFE evolutionary conservation. For this purpose, we used genomic DNA from chimpanzee and rhesus monkey. Primers were designed based on alignments made with human and murine HFE. PCR amplification was carried out and appropriate products were sequenced. The partial genomic clones from the novel HFE sequences were aligned with known human, mouse and rat HFE and phylogenetic trees were plotted. The genomic organization of chimpanzee and rhesus HFE genes was found to be identical to the human. The percentage of amino acid identity to the human ¿1, ¿2 and ¿3 HFE coding region was very high, being 98.5% for chimpanzee and 94.5% for rhesus. The phylogenetic tree of HFE and classical MHC class I ¿1 domain, shows that the HFE ¿1 domain is more conserved across species than its classical counterpart. Contrary to this, the corresponding tree plotted with the ¿3 domain gives the opposite image, with the conservation being higher within the classical MHC-I genes than within the HFE counterpart. The present finding that the ¿1 HFE domain is highly conserved indicates the importance of this domain and suggests the conservation of its ligand(s). namely transferrin receptor. The present observation that the HFE ¿3 domain is less conserved suggests that the constraints on the classical ¿3 domains may not be acting on the HFE gene. Summarizing, the novel primate HFE genomic fragments show a high degree of similarity to the human HFE reinforces the importance of the HFE gene product. A more detailed analysis of the HFE domains shows that, unlike other class I genes, the ¿1 domain is more conserved than the ¿3, reinforcing the biological importance of this domain. © 2001 Blackwell Science Ltd,.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 1