Leishmania donovani hybridisation and introgression in nature: a comparative genomic investigation
Bibliographic record
Abstract
BACKGROUND: Leishmaniasis is a neglected tropical disease transmitted by infected sandflies that results in diverse human pathologies contingent on the species of Leishmania. Leishmania donovani causes highly virulent fatal visceral leishmaniasis, whereas Leishmania major and Leishmania tropica cause less virulent, cutaneous leishmaniasis, in which the infection remains in the skin at the site of the sandfly bite. The aim of this study was to investigate the genetic basis for the emergence of L donovani strains that cause cutaneous leishmaniasis instead of visceral leishmaniasis in Sri Lanka. METHODS: All available sequencing data for L donovani samples from Asia and Africa in GenBank and the Sequence Read Archive were retrieved and filtered to select for paired-end Illumina sequencing reads with no region bias and coverage of the entire reference genome. These data were used for sequence alignments against the reference L donovani genome from Sri Lanka, and sequence analysis was used to assess the presence of genomic recombination markers and the presence of foreign genetic sequences in the genomes of L donovani isolates associated with cutaneous leishmaniasis in Sri Lanka. BLAST analysis was used to compare the genetic sequences from the Sri Lankan isolates to all genomes of Leishmania species from the Old World available in TriTrypDB, including L major and L tropica. FINDINGS: After filtering of the 1238 existing sequencing records, 684 high-quality records were used to show that 12 L donovani strains from Sri Lanka form three phylogenetic groups. In one group, the density of heterozygous variants is higher than in previously characterised Leishmania hybrid strains. BLAST analysis showed this group contains gene polymorphisms homologous with L major and L tropica genomes for 22% (2160 of 9757) to 78% (7671 of 9757) of all genes analysed. Analysis by phylogeny and BLAST showed that the L donovani-L major and L donovani-L tropica hybrid strains originated from Africa and are phylogenetically distinct from the L donovani strains in neighbouring India. INTERPRETATION: Novel L donovani strains might arise in new environments through the integration of genes from another species. On the basis of the findings of this study, we hypothesise that hybridisation with genomes from L major and L tropica, followed by recombination and introgression, contributed to the emergence of L donovani offspring capable of causing cutaneous leishmaniasis in Sri Lanka. FUNDING: Canadian Institutes of Health Research, Fonds de recherche du Québec-Santé.
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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 | 0.002 | 0.002 |
| 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) | 0.002 | 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".