ABSTRACT
The mainstream of the post-genome target-assisted breeding in crop plant species includes biofortification such as high-throughput phenotyping along with genome-based selection. Therefore, in this work, we used the Web-service Plant_SNP_TATA_Z-tester, which we have previously developed, to run a uniform in silico analysis of the transcriptional alterations of 54,013 protein-coding transcripts from 32,833 Arabidopsis thaliana L. genes caused by 871,707 SNPs located in the proximal promoter region. The analysis identified 54,993 SNPs as significantly decreasing or increasing gene expression through changes in TATA-binding protein affinity to the promoters. The existence of these SNPs in highly conserved proximal promoters may be explained as intraspecific diversity kept by the stabilizing natural selection. To support this, we hand-annotated papers on some of the Arabidopsis genes possessing these SNPs or on their orthologs in other plant species and demonstrated the effects of changes in these gene expressions on plant vital traits. We integrated in silico estimates of the TBP-promoter affinity in the AtSNP_TATAdb knowledge base and showed their significant correlations with independent in vivo experimental data. These correlations appeared to be robust to variations in statistical criteria, genomic environment of TATA box regions, plants species and growing conditions.
Subject(s)
Arabidopsis , Arabidopsis/genetics , Polymorphism, Single Nucleotide , Plant Breeding , Biomarkers , Promoter Regions, GeneticABSTRACT
Atherosclerosis is a systemic disease in which focal lesions in arteries promote the build-up of lipoproteins and cholesterol they are transporting. The development of atheroma (atherogenesis) narrows blood vessels, reduces the blood supply and leads to cardiovascular diseases. According to the World Health Organization (WHO), cardiovascular diseases are the leading cause of death, which has been especially boosted since the COVID-19 pandemic. There is a variety of contributors to atherosclerosis, including lifestyle factors and genetic predisposition. Antioxidant diets and recreational exercises act as atheroprotectors and can retard atherogenesis. The search for molecular markers of atherogenesis and atheroprotection for predictive, preventive and personalized medicine appears to be the most promising direction for the study of atherosclerosis. In this work, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis and atheroprotection. The hub genes regulating these processes have been found to be the most ancient. In silico analysis of all 5112 SNPs in their promoters has revealed 330 candidate SNP markers, which statistically significantly change the affinity of the TATA-binding protein (TBP) for these promoters. These molecular markers have made us confident that natural selection acts against underexpression of the hub genes for atherogenesis, atherosclerosis and atheroprotection. At the same time, upregulation of the one for atheroprotection promotes human health.
