Table 1_Whole genome sequencing reveals genomic diversity and evidence of hybridization in Moroccan Leishmania infantum strains.xlsx

In Morocco, Leishmania infantum is an endemic species responsible for visceral leishmaniasis (VL, fatal if untreated) as well as cutaneous leishmaniasis (CL). The number of cases and the distribution range of both forms are increasing, spreading into new areas. However, despite its clinical significance, the genomic diversity of this species remains largely overlooked. We performed whole-genome sequencing of six L. infantum strains from patients with VL, CL, or CL/HIV, as well as from dogs, and conducted comparative genomic analyses. Read depth analysis at both the chromosome and gene levels revealed isolate-specific variability in ploidy and identified gene copy number variations (CNVs), mostly in genes involved in parasite virulence and survival, all of which support the parasite’s remarkable adaptability. Principal component analysis (PCA) and SNP-based clustering revealed a notable divergence between the two cutaneous isolates and the other strains. We further confirmed the diversity of the CL/HIV strain previously studied using the MLST technique. In addition, the pronounced genomic heterogeneity observed in this strain suggests that host immune status may influence parasite diversity. The strain FA23, isolated from a CL patient exhibiting substantial SNP divergence from all other isolates, suggested a possible hybrid origin, which we confirmed using the Kraken2 package, which revealed important introgression with genome sequences from L. donovani (22.21%). These findings demonstrate that comparative genomics are instrumental in detecting hybridization signals, supporting genetic exchange as a significant evolutionary process contributing in the diversification of new CL cases caused by L. infantum.