Project description:Study of high-coverage whole-exome sequences from Amazigh (Tamazight-speakers) and non-Amazigh individuals (Arab-speakers) from Tunisia to analyze the impact of demography in functional genomic variation in the complex demographic context of North Africa. Amazigh individuals were sampled in Chenini and Douiret, and non-Amazigh individuals were sampled in Tunis.
Project description:The protozoan parasite Leishmania infantum exhibits significant genetic variability among isolates, influencing disease manifestation and treatment response. Although L. infantum is classically described as the causative agent of Visceral Leishmaniasis (VL) – often associated with immune deficiency, cases of Cutaneous Leishmaniasis (CL) caused by this species in immunocompetent individuals have been reported in different countries. With the aim to gain new insight underlying this unusual change in L. infantum tropism and pathogenicity, we applied comparative genomic and transcriptomic approaches on two canine isolates (Lcan) and two human isolates associated with CL in Tunisia. Using DNA-seq analysis, we assessed aneuploidy, gene copy number variations (CNVs), and single-nucleotide polymorphisms (SNPs) between strains. While the Lcan isolates showed close genetic similarity to the L. infantum reference strain (JPCM5), the CL isolates formed a separate, highly divergent cluster based on SNP localization and frequency, differing not only from JPCM5 but also from each other. Utilizing the metagenomics sequence classification tool Kraken, we revealed a complex hybrid nature of the LC isolates, indicating genetic introgression from both L. donovani and L. tropica. Integration of RNA-seq and DNA-seq data showed that expression differences within the LC and Lcan sample groups are largely attributable to gene dosage effects. In contrast, significant expression changes independent of gene dosage were observed in-between the LC and Lcan sample groups, indicating post-transcriptional regulation as an additional regulatory mechanism for parasite adaptation in the field. This work highlights hybridization as a potential source of phenotypic variation in L. infantum and investigates how genome instability and transcriptomic plasticity contribute together to parasite evolvability and fitness gain.
