Comprehensive study of the evolutionary history of the isoforms of the LAMTOR5 gene, associated with Hepadnaviridae virus infection.

• Grant number: 24/13048-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: November 01, 2024
• End date: October 31, 2025
• Field of knowledge: Biological Sciences - Genetics - Animal Genetics
• Principal Investigator: Juliana Helena Costa Smetana
• Grantee: Iasodara do Carmo Lima dos Santos
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Campinas , SP, Brazil

Abstract

The HBXIP protein is an important component of the Ragulator Complex, a protein pentamer thatparticipates in the regulation of the mTORC1 pathway and is associated in the pathogenesis of severalcancers. Before its identification as a monomer of the Ragulator Complex, HBXIP was already knownas an interaction partner of the Hepatitis B virus (HBx) X-protein. HBx plays a fundamental role in theinfection process by the Hepatitis B virus, which occurs mainly in the liver tissues of primates, rodentsand bats. Analyses of the human transcriptome carried out by our research group show the existenceof four different transcripts of the HBXIP protein, which differ in the amino acid sequence of the N-terminal region. The canonical isoform, with 91 amino acids (aa), is expressed in all tissues at similarrates, while the long isoform (173aa) is expressed mainly in liver tissues. In the same research, itwas found that overexpression of the HBXIP protein in hepatocytes leads to the suppression of HBxactivity. Given these results, our research group raised the hypothesis that the canonical isoform(91aa) is ancestral in mammals and the long form surged as an antagonist of HBx. In order totest this hypothesis, the evolutionary history of the short (91aa) and long (173aa) isoforms of HBXIPwas reconstructed using the genomes of 22 primate species. The results confirmed the existence ofpositive selective pressure in the N-terminal region. In 2023, however, 233 primate genomes werepublished on the NCBI database. Given this new volume of data, this research project proposesto reconstruct the evolutionary history of the two isoforms not only in primates, but onthe entire order Euarchontoglires (primates, rodents and lagomorphs). We wish to confirm the initialhypothesis that the HBXIP protein suffered positive selective pressure in primates thanks to infectionby the HBV virus, as well as that its surgiment is ancestral in the order Euarchontoglires and waslost in species not susceptible to HBV virus infection.