Frequent Homologous Recombination Events in <i>Mycobacterium tuberculosis</i> PE/PPE Multigene Families: Potential Role in Antigenic Variability
Bibliographic record
Abstract
The PE and PPE (PE/PPE) multigene families of Mycobacterium tuberculosis are particularly GC-rich and share extensive homologous repetitive sequences. We hypothesized that they may undergo homologous recombination events, a mechanism rarely described in the natural evolution of mycobacteria. To test our hypothesis, we developed a specific oligonucleotide-based microarray targeting nearly all of the PE/PPE genes, aimed at detecting signals for homologous recombination. Such a microarray has never before been reported due to the multiplicity and highly repetitive and homologous nature of these sequences. Application of the microarray to a collection of M. tuberculosis clinical isolates (n = 33) representing prevalent spoligotype strain families in Tunisia allowed successful detection of six deleted genomic regions involving a total of two PE and seven PPE genes. Some of these deleted genes are known to be immunodominant or involved in virulence. The four precisely determined deletions were flanked by 400- to 500-bp stretches of nearly identical sequences lying mainly at the conserved N-terminal region of the PE/PPE genes. These highly homologous sequences thus serve as substrates to mediate both intergenic and intragenic homologous recombination events, indicating an important function in generating strain variation. Importantly, all recombination events yielded a new in-frame fusion chimeric gene. Hence, homologous recombination within and between PE/PPE genes likely increased their antigenic variability, which may have profound implications in pathogenicity and/or host adaptation. The finding of high prevalence (approximately 45% and approximately 58%) for at least two of the genomic deletions suggests that they likely confer advantageous biological attributes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".