AUTHOR=Gómez-González Paula Josefina , Grabowska Anna D. , Tientcheu Leopold D. , Tsolaki Anthony G. , Hibberd Martin L. , Campino Susana , Phelan Jody E. , Clark Taane G. 

TITLE=Functional genetic variation in pe/ppe genes contributes to diversity in Mycobacterium tuberculosis lineages and potential interactions with the human host

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1244319

DOI=10.3389/fmicb.2023.1244319

ISSN=1664-302X

ABSTRACT=Around 10% of the coding potential of Mycobacterium tuberculosis is constituted by two poorly understood gene families, the pe and ppe loci, thought be involved in host-pathogen interactions. Their repetitive nature and high GC content have hindered sequence analysis, leading to exclusion from whole-genome studies. To investigate the genetic diversity of the 169 pe/ppe genes, we performed a sequence analysis across 73 long-read assemblies representing seven different lineages of M. tuberculosis. The pe/ppe genes were classified into three groups based on the level of protein sequence conservation, finding that >50% were conserved, with indels in pe_pgrs and ppe_mptr sub-families being major drivers of structural variation. Gene rearrangements were observed between pe and pe_pgrs genes.Inter-lineage diversity revealed lineage-specific SNPs and indels, suggesting they are phylogenetically informative. Overall, improving our knowledge of these complex gene families may have insights into pathogenicity and inform the development of much-needed tools for tuberculosis control.