Unraveling the Palindromic and Non-Palindromic Motifs of Retroviral Integration Site Sequences by Statistical Mixture Models

Abstract

AbstractA weak palindromic nucleotide motif is the hallmark of retroviral integration site alignments. Previously, the motifs were explained by an overlap of the non-palindromic motif being present on one of the half-site of targeted sequences. Here, we applied multicomponent mixture models to integration site sequences of diverse retroviruses. We demonstrate that the weak palindromic motifs result from a combination of independent sub-motifs restricted to only a few positions proximal to the site of integration. The sub-motifs are formed by either palindrome-forming nucleotide preference or nucleotide exclusion. Using the mixture models, we also identified HIV-1-favored palindromic sequences in Alu repeats serving as hotspots for integration. Our work presents a novel statistical approach to the analysis of retroviral integration site sequences, which can form a valuable tool in the analysis of DNA motifs. The presented results shed new light on the selection of target site sequences for retroviral integration.