Application of next generation sequencing (NGS) for descriptive analysis of 30 genomes of Leishmania infantum isolates in Middle-North Brazil

Carvalho, Kátia Silene Sousa; Júnior, Wilson José da Silva; Regueira-Neto, Marcos da Silveira; Silva, Vladimir Costa; Júnior, Sérgio de Sá Leitão Paiva; Balbino, Valdir Queiroz; Costa, Dorcas Lamounier; Costa, Carlos Henrique Nery

doi:10.1038/s41598-020-68953-9

Cited by 15 publications

(17 citation statements)

References 57 publications

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“…Here, we sequenced 93 strains of L. infantum from Brazil, contributing to a worldwide collection of L. donovani complex isolates along with previous analyses ( Imamura et al 2016 ; Carnielli et al 2018 ; Zackay et al 2018 ; Franssen et al 2020 ). Our analysis of this population is consistent with these previous studies, showing that the L. infantum population in Brazil contains very little genetic diversity ( Carvalho et al 2020 ; Schwabl et al 2021 ). A consistent observation in analysis of this species complex is that populations from East Africa, India, and Brazil are substantially genetically differentiated, a result that we reiterate here ( fig.…”

Section: Discussionsupporting

confidence: 92%

Candidates for Balancing Selection inLeishmania donovaniComplex Parasites

Grace

Forrester

Silva

et al. 2021

Genome Biology and Evolution

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The Leishmania donovani species complex are the causative agents of visceral leishmaniasis, which cause 20-40,000 fatalities a year. Here, we conduct a screen for balancing selection in this species complex. We used 384 publicly-available L. donovani and L. infantum genomes, and sequence 93 isolates of L. infantum from Brazil to describe the global diversity of this species complex. We identify five genetically-distinct populations that are sufficiently represented by genomic data to search for signatures of selection. We find that signals of balancing selection are generally not shared between populations, consistent with transient adaptive events, rather than long-term balancing selection. We then apply multiple diversity metrics to identify candidate genes with robust signatures of balancing selection, identifying a curated set of 24 genes with robust signatures. These include zeta toxin, nodulin-like and flagellum attachment proteins. This study highlights the extent of genetic divergence between L. donovani complex parasites and provides genes for further study.

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Section: Discussionsupporting

confidence: 92%

Candidates for Balancing Selection inLeishmania donovaniComplex Parasites

Grace

Forrester

Silva

et al. 2021

Genome Biology and Evolution

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“…Here we sequence 93 strains of L. infantum from Brazil, contributing to a worldwide collection of L. donovani complex isolates along with previous analyses (Imamura et al , 2016;Carnielli et al , 2018;Zackay et al , 2018;Franssen et al , 2020) . Our analysis is consistent with these previous studies showing that the L. infantum population in Brazil contains very little genetic diversity (Carvalho et al , 2020;Schwabl et al , 2021 (Tajima, 1989) . These analytic tools, and the use of multiple populations should produce an analysis that is at least as reliable as previous screens for balancing selection searches within parasites such as…”

Section: Discussionsupporting

confidence: 93%

Multiple targets of balancing selection inLeishmania donovanicomplex parasites

Grace

Forrester

et al. 2021

Preprint

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The Leishmania donovani species complex are the causative agents of visceral leishmaniasis, which cause 20-40,000 fatalities a year. Here, we conduct a screen for balancing selection in this specie complex. We sequence 93 isolates of L. infantum from Brazil and used 387 publicly-available L. donovani and L. infantum genomes, to describe the global diversity of this species complex. We identify five genetically-distinct populations that are sufficiently represented by genomic data to search for signatures of selection. We show that multiple metrics identify genes with robust signatures of balancing selection. We produce a curated set of 19 genes with robust signatures, including zeta toxin, nodulin-like and flagellum attachment proteins. Candidate genes were generally not shared between populations, consistent with divergent rather than long-term balancing selection in these species. This study highlights the extent of genetic divergence between L. donovani complex parasites and provides candidate genes for further study.

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“…For the study, WGS genomic reads (DNA-seq) for 60 L. infantum field isolates, generated by several research groups and deposited in public databases, were used. Thus, using Illumina reads deposited in the ENA project PRJNA589999 [ 61 ], 28 complete maxicircle CR sequences were assembled and compiled in Mendeley Data [ 62 ]. Another three maxicircles were assembled from the NGS data generated by Bussotti et al [ 63 ] and compiled in Mendeley Data [ 64 ].…”

Section: Resultsmentioning

confidence: 99%

Assembly of a Large Collection of Maxicircle Sequences and Their Usefulness for Leishmania Taxonomy and Strain Typing

Solana

Chicharro

García

et al. 2022

Genes

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Parasites of medical importance, such as Leishmania and Trypanosoma, are characterized by the presence of thousands of circular DNA molecules forming a structure known as kinetoplast, within the mitochondria. The maxicircles, which are equivalent to the mitochondrial genome in other eukaryotes, have been proposed as a promising phylogenetic marker. Using whole-DNA sequencing data, it is also possible to assemble maxicircle sequences as shown here and in previous works. In this study, based on data available in public databases and using a bioinformatics workflow previously reported by our group, we assembled the complete coding region of the maxicircles for 26 prototypical strains of trypanosomatid species. Phylogenetic analysis based on this dataset resulted in a robust tree showing an accurate taxonomy of kinetoplastids, which was also able to discern between closely related Leishmania species that are usually difficult to discriminate by classical methodologies. In addition, we provide a dataset of the maxicircle sequences of 60 Leishmania infantum field isolates from America, Western Europe, North Africa, and Eastern Europe. In agreement with previous studies, our data indicate that L. infantum parasites from Brazil are highly homogeneous and closely related to European strains, which were transferred there during the discovery of America. However, this study showed the existence of different L. infantum populations/clades within the Mediterranean region. A maxicircle signature for each clade has been established. Interestingly, two L. infantum clades were found coexisting in the same region of Spain, one similar to the American strains, represented by the Spanish JPCM5 reference strain, and the other, named “non-JPC like”, may be related to an important leishmaniasis outbreak that occurred in Madrid a few years ago. In conclusion, the maxicircle sequence emerges as a robust molecular marker for phylogenetic analysis and species typing within the kinetoplastids, which also has the potential to discriminate intraspecific variability.

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Application of next generation sequencing (NGS) for descriptive analysis of 30 genomes of Leishmania infantum isolates in Middle-North Brazil

Cited by 15 publications

References 57 publications

Candidates for Balancing Selection inLeishmania donovaniComplex Parasites

Candidates for Balancing Selection inLeishmania donovaniComplex Parasites

Multiple targets of balancing selection inLeishmania donovanicomplex parasites

Assembly of a Large Collection of Maxicircle Sequences and Their Usefulness for Leishmania Taxonomy and Strain Typing

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