The Genome Sequence of Leishmania (Leishmania) amazonensis: Functional Annotation and Extended Analysis of Gene Models

Abstract

We present the sequencing and annotation of the Leishmania (Leishmania) amazonensis genome, an etiological agent of human cutaneous leishmaniasis in the Amazon region of Brazil. L. (L.) amazonensis shares features with Leishmania (L.) mexicana but also exhibits unique characteristics regarding geographical distribution and clinical manifestations of cutaneous lesions (e.g. borderline disseminated cutaneous leishmaniasis). Predicted genes were scored for orthologous gene families and conserved domains in comparison with other human pathogenic Leishmania spp. Carboxypeptidase, aminotransferase, and 3′-nucleotidase genes and ATPase, thioredoxin, and chaperone-related domains were represented more abundantly in L. (L.) amazonensis and L. (L.) mexicana species. Phylogenetic analysis revealed that these two species share groups of amastin surface proteins unique to the genus that could be related to specific features of disease outcomes and host cell interactions. Additionally, we describe a hypothetical hybrid interactome of potentially secreted L. (L.) amazonensis proteins and host proteins under the assumption that parasite factors mimic their mammalian counterparts. The model predicts an interaction between an L. (L.) amazonensis heat-shock protein and mammalian Toll-like receptor 9, which is implicated in important immune responses such as cytokine and nitric oxide production. The analysis presented here represents valuable information for future studies of leishmaniasis pathogenicity and treatment.

Comparative genomics of canine-isolated Leishmania (Leishmania) amazonensis from an endemic focus of visceral leishmaniasis in Governador Valadares, southeastern Brazil

“…This method resulted in 3,584 and 3,236 contigs with an N50 of 29,346 bp and 26,692 bp for isolates S3 and S6, respectively (Table 1). While still a draft, our assembly is more contiguous than either of the published L. (L.) amazonensis M2269 assemblies1516. These contigs comprised more than 30.5 Mbp, which is slightly larger than the current L. (L.) amazonensis M2269 reference genome (version from 2013-07-25) and closer to the expected size for Leishmania genomes of 32 Mbp19.…”

“…The L. (L.) infantum JPCM517 , L. (L.) mexicana U110319 and L. (L.) amazonensis M226915 reference genomes were downloaded from version 10 of the TriTrypDB database (http://tritrypdb.org/) for the mapping and genome assembly steps.…”

“…Two different genome assemblies of the same L. (L.) amazonensis isolate (MHOM/BR/71973/M2269) have previously been published1516. The M2269 isolate was obtained from a human cutaneous lesion in Para state, Brazil in 197315.…”

Comparison of codon usage bias across Leishmania and Trypanosomatids to understand mRNA secondary structure, relative protein abundance and pathway functions

“…Among 7 completely sequenced Leishmania genomes published so far, six are of species known to infect humans [1][2][3][4][5][6]. Further, there is a distinct speciesspecific heterogeneity observed in clinical manifestations of different Leishmania species within the human host.…”

Neglected Tropical Diseases in the Post-Genomic Era

“…Genomes from different subspecies and strains/isolates also available [82,156,157]. http://tritrypdb.org [148].…”