High Throughput Chromosome Conformation Capture identifies differential genome organization in virulent and avirulent strains of Mycobacterium tuberculosis

Recent studies have shown that three-dimensional architecture of bacterial chromatin plays an important role in gene expression regulation. However, genome topological organization in Mycobacterium tuberculosis (M. tuberculosis), the etiologic agent of tuberculosis, remains unknown. On the other hand, exact mechanism of differential pathogenesis in the canonical strains of M. tuberculosis H37Rv and H37Ra remains poorly understood in terms of their raw sequences. In this context, a detailed contact map from a Hi-C experiment is a candidate for what bridges the gap. Here we present the first comprehensive report on genome-wide contact maps between regions of H37Rv and H37Ra genomes. We tracked differences between the genome architectures of H37Rv and H37Ra, which could possibly explain the virulence attenuation in H37Ra. We confirm the existence of a differential organization between the two strains most significantly a higher Chromosome Interacting Domain (CID) size in attenuated H37Ra strain. CID boundaries are also found enriched with highly expressed genes and with higher operon density in H37Rv. Furthermore, most of the differentially expressed PE/PPE genes were present near the CID boundaries in H37Rv and not in H37Ra. Collectively our study proposes a differential genomic topological pattern between H37Rv and H37Ra, which could explain the virulence attenuation in H37Ra.