P68

The evolution of the Mycobacterium tuberculosis complex (MTBc) is thought to be clonal, with strains of the same lineage differing only by point mutations and small indels. However, recent studies on lineage 5 have shown large gene content differences between strains of this lineage, challenging this paradigm of within-lineage comparative genomics.

In this study, we analyse the gene content of MTBc lineage 4, the most widespread global lineage and responsible for most tuberculosis cases. We reconstructed L4 pangenome using seven complete genomes from different L4 sub-lineages and the reference genome H37Rv.

We found 3,909 genes core to all eight genomes and a further 113 genes that were differentially present in one to seven genomes. The function was not known for 60% of these accessory genes, highlighting the need for better annotation of the MTBc. This analysis was then expanded to representative of all known sub-lineages of L4 using clinical isolates. The core genome of this dataset was 3,643 genes with 410 genes in the accessory genome.

In conclusion, our data show that the accessory genome of the L4 is larger than previously thought. This finding can be crucial to understanding pathobiological elements, such as virulence and the transmissibility of MTBc strains and the clinical picture that they produce. Furthermore, using H37Rv as a reference may result in gene mapping loss, even though it is of the same lineage, thus limiting our understanding of the molecular evolution and genetic features of MTBc strains.