Genomic Flexibility Through Extrachromosomal Amplifications: A <i>Leishmania</i> Survival Strategy
Bibliographic record
Abstract
Abstract Leishmania parasites modulate gene copy number through extrachromosomal DNA (ecDNA) amplification, enabling adaptation to environmental stress. Under drug pressure, both linear and circular ecDNA amplifications (amplicons) carrying resistance genes emerge. However, how these ecDNA structures form, diversify, and coexist remains poorly understood. Here, using experimental evolution and Oxford Nanopore long-read sequencing, we show that a single clonal population of drug resistant Leishmania produces a variety of linear and circular amplicons. As antimonial pressure increases, linear amplicons transition into circular forms, with high-stress conditions favoring circular amplicons carrying at least two copies of the resistance gene. Using the Nanopore long reads, we map recombination events driving linear and circular amplicon formation. Our model suggests that gene duplication in the amplicons originates from inter-chromatid homologous recombination, leading to an intermediate intra-chromosomal duplication, followed by a second homologous recombination event. Additionally, different Leishmania species exhibited distinct biases toward linear or circular amplification under identical drug conditions, suggesting species-specific adaptive strategies. Together, these findings define recombination-driven ecDNA dynamics as a central axis of genomic plasticity in Leishmania and underscore the potential for targeting ecDNA in therapeutic and diagnostic strategies against Leishmania and related pathogens.
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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 | 0.000 |
| 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 | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".