Candidates for Balancing Selection inLeishmania donovaniComplex Parasites

Abstract

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.

Tissue Specific Dual RNA-Seq Defines Host–Parasite Interplay in Murine Visceral Leishmaniasis Caused by Leishmania donovani and Leishmania infantum

“…Ethiopian L. donovani LV9 (MHOM/ET/67/HU3) and Brazilian L. infantum NLC (MHOM/BR/2005/NLC) were chosen for this study due to their geographical and phylogenetic divergence ( 22 , 23 ). Indeed, Brazilian L. infantum isolates have been shown to have much lower nucleotide diversity compared to Indian and African L. donovani ( 23 ).…”

“…Ethiopian L. donovani LV9 (MHOM/ET/67/HU3) and Brazilian L. infantum NLC (MHOM/BR/2005/NLC) were chosen for this study due to their geographical and phylogenetic divergence ( 22 , 23 ). Indeed, Brazilian L. infantum isolates have been shown to have much lower nucleotide diversity compared to Indian and African L. donovani ( 23 ). The parasites were grown as promastigotes in modified Eagle’s medium, designated HOMEM (Thermo Fisher Scientific, Waltham, MA, USA), that was supplemented with 10% heat-inactivated fetal bovine serum (FBS, Thermo Fisher Scientific) and incubated at 25°C.…”

“…Likewise, although both L. donovani ( 20 ) and L. infantum ( 21 ) have been well characterized in terms of gene expression related to stage specific differentiation, it is not known if these two parasites react similarly to the stresses associated with mammalian infection. L. donovani and L. infantum are geographically and phylogenetic divergent ( 22 , 23 ), while having similar parasitism in mice, infecting liver, spleen, and bone marrow ( 17 , 18 ).…”

Tissue specific dual RNA-seq defines host-parasite interplay in murine visceral leishmaniasis caused by Leishmania donovani and Leishmania infantum

“…Ethiopian L. donovani LV9 (MHOM/ET/67/HU3) and Brazilian L. infantum NLC (MHOM/BR/2005/NLC) were chosen for this study due to their geographical and phylogenetic divergence (54, 55). Indeed, Brazilian L. infantum isolates have been shown to have much lower nucleotide diversity compared to Indian and African L. donovani (55). The parasites were grown as promastigotes in modified Eagle’s medium, designated HOMEM (Thermo Fisher Scientific, Waltham, MA, USA), that was supplemented with 10% heat-inactivated fetal bovine serum (FBS, Thermo Fisher Scientific) and incubated at 25 °C.…”

“…Ethiopian L. donovani LV9 (MHOM/ET/67/HU3) and Brazilian L. infantum NLC (MHOM/BR/2005/NLC) were chosen for this study due to their geographical and phylogenetic divergence (54, 55). Indeed, Brazilian L. infantum isolates have been shown to have much lower nucleotide diversity compared to Indian and African L. donovani (55).…”