In silico Analysis of 7-Dehydrocholesterol Reductase Gene (Sl7-DR2) in Tomato: Linking Cholesterol Metabolism to Vitamin D Pathway

Abstract

Tomatoes are the most popular vegetable crop worldwide and contain many health-promoting compounds. Most foods contain very little amount of vitamin D, and plants are very poor sources in the production of vitamin D. The 7-dehydrocholesterol reductase gene (Sl7-DR2) is responsible for the accumulation of 7-dehydrocholesterol, which is a precursor for vitamin D3 synthesis. This gene is present in different plant species and plays a role in cholesterol metabolism as well as it links with the vitamin D pathway by inhibiting its actual function in the synthesis of cholesterol. In this study, sequencing analysis of the gene using multiple sequence alignment provided information about its similarity and their conserved sequence regions in different plant species. Using MEGA11 software, the phylogenetic analysis of this gene was done and it showed that, this gene present in chromosome 6 and chromosome 1 of Solanum lycopersicum has a close resemblance with Solanum tuberosum and Datura stramonium respectively. The physiochemical characteristics of Sl7-DR2 were analyzed by using the Expasy protparam tool. Functional annotation and secondary structure analysis of Sl7-DR2 were done using the Pfam, STRING, and SOPMA databases. The results obtained from this analysis showed that the protein was stable and has a low GRAVY Index indicating its higher affinity to water and the secondary structure analysis predicts the robust nature of this protein and the STRING analysis gave information related to proteins that are involved in the sterol pathway and their functions. These tools characterized the protein function of the Sl7-DR2 gene and studied the role of 7-dehydrocholesterol reductase in converting 7-dehydrocholesterol to vitamin D3 and its role in cholesterol metabolism. The pathway analysis using the Reactome database helps in characterizing the network between the cholesterol and vitamin D pathway. The 3D structure of the Sl7-DR2 protein was predicted using an ab initio approach, Robetta, and the predicted structure was validated using the SAVESv6.0 (PROCHECK) server. The predicted model has 90.8% of total residues present in the most favoured regions and showed high readability and quality. These analyses demonstrated the significance of this gene in the vitamin D pathway and its potential for human health in preventing various diseases.