SNPS in the Hiv-1 Tata Box and the Aids Pandemic

Abstract

Evolutionary trends have been examined in 146 HIV-1 forms (2662 copies, 2311 isolates) polymorphic for the TATA box using the "DNA sequence-->affinity for TBP" regression (TBP is the TATA binding protein). As a result, a statistically significant excess of low-affinity TATA box HIV-1 variants corresponding to a low level of both basal and TAT-dependent expression and, consequently, slow replication of HIV-1 have been detected. A detailed analysis revealed that the excess of slowly replicating HIV-1 is associated with the subtype E-associated TATA box core sequence "CATAAAA". Principal Component Analysis performed on 2662 HIV-1 TATA box copies in 70 countries revealed the presence of two principal components, PC1 (75.7% of the variance) and PC2 (23.3% of the variance). They indicate that each of these countries is specifically associated with one of the following trends in HIV-1 evolution: neutral drift around the normal TATA box; neutral drift around the slowly replicating TATA box core sequence (phylogenetic inertia); an adaptive increase in the frequency of the slowly replicating form.

Sequence-based prediction of transcription upregulation by auxin in plants

“…(1). We evaluated the K TBP=PROMOTER term using the -value that is the natural logarithm of the maximum predicted TBP/DNA binding a±nity 46 to gene's region [À70; À20] upstream from transcription start site. Most experimentally proven TATA-boxes reside in this region.…”

How to Use SNP_TATA_Comparator to Find a Significant Change in Gene Expression Caused by the Regulatory SNP of This Gene’s Promoter via a Change in Affinity of the TATA-Binding Protein for This Promoter

“…Then we confirmed predictions of this three-step empirical predictive bioinformatics model [ 47 ] at equilibrium [ 50 ], without equilibrium [ 51 ], and in real time [ 52 , 53 ] in vitro . Additionally, we compiled a set of SNPs in the TBP-binding sites associated with human diseases [ 54 ], including the AIDS pandemic [ 55 ], and with commercially important traits of plants and animals [ 56 ]. Then, we confirmed the three-step predictions by means of these SNPs [ 57 ] and by means of transcriptomes of the human brain [ 58 ], the auxin response in plants [ 59 , 60 ], and the data from 68 independent experiments (for review, see [ 61 ]).…”

In vitro examining the existing prognoses how TBP binds to TATA with SNP associated with human diseases

“…Identification of the previously unidentified source of the consistent in silico underestimation of the amount of damage caused to the regulatory regions of genes with SNPs makes us expect that a standardized examination of all the 237 TATA box SNPs, associated with human diseases [17], regional patterns of the AIDS pandemic [16], animal and plant traits, which are valuable with respect to breeding purposes [18], and newly discovered mutations in TATA boxes will allow us to look into the mechanisms of ТВР/ТАТА binding and improve the research quality of the computer-aided tools used for analysis and prediction of SNPs in the regulatory regions of human genes.…”

“…Although the ТАТА box is a "semi-conservative" site, no-neutral SNPs in it are quite a common occurrence in various species. Thus, in silico analysis of the current content of the GenBank database revealed 146 SNPs of the HIV-1 TATA box, of which 63 could significantly modify the replicative potential of the virus and were associated with the regional patterns of the AIDS pandemic in 70 countries [16]. Literature data suggest that 53 SNPs in the ТАТА boxes of various human genes are associated with the propensity for diseases [17], 38 SNPs are associated with various animal and plant traits valuable with respect to breeding purposes [18].…”