Systems-Level Comparative Bioinformatics Analysis Of Liver-Associated Genes (ALB, TNF, F8, VDR, and FASN) Across Vertebrate Species

Abstract

The liver is a major metabolic organ that regulates nutrient homeostasis, immune response, coagulation, detoxification and endocrine function. For studying evolutionary conservation and structural-functional difference of vital hepatic genes among vertebrates, we undertook a comparative bioinformatics research on five major liver-associated genes (ALB, TNF, F8, VDR and FASN) in five species of vertebrates: Homo sapiens, Bos taurus, Canis lupus familiaris, Mus musculus and Gallus gallus. Nucleotide sequences were obtained from the NCBI database and aligned using MEGA 12 by ClustalW. Phylogenetic trees were generated with the Maximum likelihood method based on Tamura-Nei model. Amino acid sequences of proteins were translated by ExPASy Translate tool and confirmed by BLASTp homology search. Identification of conserved domains was performed with the NCBI CDD and comparisons to structures pooled to PDB templates. Phylogenetic separation among mammalian species was detected, since human, cow and dog formed closely related clusters and mouse had a moderate divergence with chicken as the farthest related species. ALB and FASN are the most conserved across species, indicating strong purifying selection for their metabolic roles. Contrastingly, TNF and F8 had more divergent sequences particularly in the avian, possibly representing lineage-specific adaptations in immune signaling or coagulation machinery. Conserved domain analysis verified the retention of conserved functional motifs such as ligand-binding sites, putative/receptor-interaction site interfaces, coagulation domains and catalytic regions for fatty acid synthesis. These results illustrate remarkable evolutionary conservation of liver-enriched functional genes among vertebrates and different divergence in species phylogeny and physiological adaptation. The work demonstrates the potential of cross-species in silico approaches to study functional conservation, comparative anatomy and use as a framework for translation and evolutionary studies in liver.