Fig. 8

HIV-1 LTR demonstrates high divergence both upstream and downstream of the transcription start site. HIV-1 long terminal repeat (LTR) sequences were sorted into R5 (n = 615) and X4 (n = 35) populations according to the predicted co-receptor usage of the co-linear V3 region. a The diversity index at order = 1 was calculated for each position for both R5 (red) and X4 (blue) LTR sequence populations, numbered according to the HXB2 reference sequence. b Following the same approach applied for amino acid analysis, Jensen–Shannon divergence between R5 and X4 LTR sequences was computed for each nucleotide position and plotted. Statistically divergent positions were plotted in red and identified throughout the LTR, both upstream and downstream of the transcriptional start site and within transcription factor binding sites. A Monte Carlo permutation simulation was performed to randomly group LTR sequences and calculate a distribution of expected Jensen–Shannon divergence values, with the full range (light blue) and interquartile range (dark blue) of the distribution plotted across each position of the LTR