Dataset Information

Intraspecific Genomic Divergence and Minor Structural Variations in Leishmania (Viannia) panamensis.

ABSTRACT: Leishmania (Viannia) panamensis is one of the most important Leishmania species associated with cutaneous leishmaniasis (CL) in Latin America. Despite its wide geographic distribution and pathogenic potential in humans and animals, the genomic variability of this species is low compared with other Leishmania species circulating in the same geographical area. No studies have reported a detailed analysis of the whole genome of L. panamensis from clinical isolates using DNA high-throughput sequencing to clarify its intraspecific genomic variability or plausible divergence. Therefore, this study aimed to evaluate the intraspecific genomic variability of L. panamensis from Colombia and Panama. A total of 22 genomes were analyzed, 19 from Colombian patients with CL and three genomes from Panama obtained from public databases. The phylogenomic analysis revealed the potential existence of three well-supported clades as evidence of intraspecific divergence. Additionally, the whole-genome analysis showed low structural variations in terms of ploidy, copy number variations, and single-nucleotide polymorphisms (SNPs). SNPs shared among all clades were identified, revealing their importance in different biological processes of L. panamensis. The findings not only expand our knowledge of intraspecific genomic variability of one of the most important Leishmania species in South America but also highlights the possible existence of different clades/lineages/subpopulations across a geographic scale.

SUBMITTER: Patino LH

PROVIDER: S-EPMC7140786 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Intraspecific Genomic Divergence and Minor Structural Variations in Leishmania (Viannia) panamensis.

Patino Luz H LH Muñoz Marina M Muskus Carlos C Méndez Claudia C Ramírez Juan David JD

Genes 20200227 3

Leishmania (Viannia) panamensis is one of the most important Leishmania species associated with cutaneous leishmaniasis (CL) in Latin America. Despite its wide geographic distribution and pathogenic potential in humans and animals, the genomic variability of this species is low compared with other Leishmania species circulating in the same geographical area. No studies have reported a detailed analysis of the whole genome of L. panamensis from clinical isolates using ...[more]

PMID: 32120946

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Project description:BackgroundThe Leishmania (Viannia) braziliensis complex is responsible for most cases of New World tegumentary leishmaniasis. This complex includes two closely related species but with different geographic distribution and disease phenotypes, L. (V.) peruviana and L. (V.) braziliensis. However, the genetic basis of these differences is not well understood and the status of L. (V.) peruviana as distinct species has been questioned by some. Here we sequenced the genomes of two L. (V.) peruviana isolates (LEM1537 and PAB-4377) using Illumina high throughput sequencing and performed comparative analyses against the L. (V.) braziliensis M2904 reference genome. Comparisons were focused on the detection of Single Nucleotide Polymorphisms (SNPs), insertions and deletions (INDELs), aneuploidy and gene copy number variations.ResultsWe found 94,070 variants shared by both L. (V.) peruviana isolates (144,079 in PAB-4377 and 136,946 in LEM1537) against the L. (V.) braziliensis M2904 reference genome while only 26,853 variants separated both L. (V.) peruviana genomes. Analysis in coding sequences detected 26,750 SNPs and 1,513 indels shared by both L. (V.) peruviana isolates against L. (V.) braziliensis M2904 and revealed two L. (V.) braziliensis pseudogenes that are likely to have coding potential in L. (V.) peruviana. Chromosomal read density and allele frequency profiling showed a heterogeneous pattern of aneuploidy with an overall disomic tendency in both L. (V.) peruviana isolates, in contrast with a trisomic pattern in the L. (V.) braziliensis M2904 reference. Read depth analysis allowed us to detect more than 368 gene expansions and 14 expanded gene arrays in L. (V.) peruviana, and the likely absence of expanded amastin gene arrays.ConclusionsThe greater numbers of interspecific SNP/indel differences between L. (V.) peruviana and L. (V.) braziliensis and the presence of different gene and chromosome copy number variations support the classification of both organisms as closely related but distinct species. The extensive nucleotide polymorphisms and differences in gene and chromosome copy numbers in L. (V.) peruviana suggests the possibility that these may contribute to some of the unique features of its biology, including a lower pathology and lack of mucosal development.

Project description:Leishmania (Viannia) braziliensis is an important Leishmania species circulating in several Central and South American countries. Among Leishmania species circulating in Brazil, Argentina and Colombia, L. braziliensis has the highest genomic variability. However, genomic variability at the whole genome level has been only studied in Brazilian and Peruvian isolates; to date, no Colombian isolates have been studied. Considering that in Colombia, L. braziliensis is a species with great clinical and therapeutic relevance, as well as the role of genetic variability in the epidemiology of leishmaniasis, we analyzed and evaluated intraspecific genomic variability of L. braziliensis from Colombian and Bolivian isolates and compared them with Brazilian isolates. Twenty-one genomes were analyzed, six from Colombian patients, one from a Bolivian patient, and 14 Brazilian isolates downloaded from public databases. The results obtained of Phylogenomic analysis showed the existence of four well-supported clades, which evidenced intraspecific variability. The whole-genome analysis revealed structural variations in the somy, mainly in the Brazilian genomes (clade 1 and clade 3), low copy number variations, and a moderate number of single-nucleotide polymorphisms (SNPs) in all genomes analyzed. Interestingly, the genomes belonging to clades 2 and 3 from Colombia and Brazil, respectively, were characterized by low heterozygosity (~90% of SNP loci were homozygous) and regions suggestive of loss of heterozygosity (LOH). Additionally, we observed the drastic whole genome loss of heterozygosity and possible hybridization events in one genome belonging to clade 4. Unique/shared SNPs between and within the four clades were identified, revealing the importance of some of them in biological processes of L. braziliensis. Our analyses demonstrate high genomic variability of L. braziliensis in different regions of South America, mainly in Colombia and suggest that this species exhibits striking genomic diversity and a capacity of genomic hybridization; additionally, this is the first study to report whole-genome sequences of Colombian L. braziliensis isolates.

Dataset Information

Intraspecific Genomic Divergence and Minor Structural Variations in Leishmania (Viannia) panamensis.

Publications

Intraspecific Genomic Divergence and Minor Structural Variations in <i>Leishmania (Viannia) panamensis</i>.

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