Pseudogenomic Insights Into The Evolution Of Mycobacterium Ulcerans
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Date
2024
Journal Title
Journal ISSN
Volume Title
Publisher
BMC Genomics
Abstract
Background: Buruli ulcer (BU) disease, caused by Mycobacterium ulcerans (MU) and characterized by necrotic ulcers
is still a health problem in Africa and Australia. The genome of the bacterium has several pseudogenes due to recent
evolutionary events and environmental pressures. Pseudogenes are genetic elements regarded as non-essential in
bacteria, however, are less studied due to limited available tools to provide understanding of their evolution and
roles in MU pathogenicity.
Results This study developed a bioinformatic pipeline to profile the pseudogenomes of sequenced MU
clinical isolates from different countries. One hundred and seventy-two MU genomes analyzed revealed that
The pseudogenomes of African strains corresponded to the two African lineages 1 and 2. Pseudogenomes were lineages
and location-specific, and African lineage 1 was further divided into A and B. Lineage 2 had less relaxation in positive
selection than lineage 1, which may signify different evolutionary points. Based on the Gil-Latorre model, African
strains may be in the latter stages of evolutionary adaptation and are adapting to an environment rich in metabolic
resources with a lower temperature and decreased UV radiation. The environment fosters oxidative metabolism and
MU may be less reliant on some secondary metabolites. In-house pseudogenomes from Ghana and Cote d’Ivoire
were different from other African strains; however, they were identified as African strains.
Conclusion Our bioinformatic pipeline provides pseudogenomic insights to complement other whole genome
analyses, providing a better view of the evolution of the genome of MU and suggesting an adaptation model which
is important in understanding transmission. MU pseudogene profiles vary based on lineage and country, and an
apparent reduction in insertion sequences used for the detection of MU, which may adversely affect the sensitivity of
diagnosis.
Significance
Prevention and treatment of Buruli ulcer is still a problem but large whole genome datasets on M. ulcerans are
readily available. However, genomic studies fail to thoroughly investigate pseudogenes to probe evolutionary
changes in the bacteria, and this can be attributed to the lack of bioinformatic tools. This work studied
pseudogenes in Mycobacterium ulcerans (MU) to understand its adapted niche and evolutionary differences across
African strains. Our results suggest that an MU niche-adapted model is important in understanding transmission. Also, MU
pseudogene profiles vary based on lineage and country, suggesting their influence on pseudogenization patterns
Description
Research Article
Keywords
Buruli ulcer, Evolution, Niche adaptation model