Comparative analyses of whole genome sequences of Leishmania infantum isolates from humans and dogs in northeastern Brazil

Abstract

The genomic sequences of 20 Leishmania infantum isolates collected in northeastern Brazil were compared with each other and with the available genomic sequences of 29 L. infantum/donovani isolates from Nepal and Turkey. The Brazilian isolates were obtained in the early 1990s or since 2009 from patients with visceral or non-ulcerating cutaneous leishmaniasis, asymptomatic humans, or dogs with visceral leishmaniasis. Two isolates were from the blood and bone marrow of the same visceral leishmaniasis patient. All 20 genomic sequences display 99.95% identity with each other and slightly less identity with a reference L. infantum genome from a Spanish isolate. Despite the high identity, analysis of individual differences among the 32 million base pair genomes showed sufficient variation to allow the isolates to be clustered based on the primary sequence. A major source of variation detected was in chromosome somy, with only four of the 36 chromosomes being predominantly disomic in all 49 isolates examined. In contrast, chromosome 31 was predominantly tetrasomic/pentasomic, consistent with its regions of synteny on two different disomic chromosomes of Trypanosoma brucei. In the Brazilian isolates, evidence for recombination was detected in 27 of the 36 chromosomes. Clustering analyses suggested two populations, in which two of the five older isolates from the 1990s clustered with a majority of recent isolates. Overall the analyses do not suggest individual sequence variants account for differences in clinical outcome or adaptation to different hosts. For the first known time, DNA of isolates from asymptomatic subjects were sequenced. Of interest, these displayed lower diversity than isolates from symptomatic subjects, an observation that deserves further investigation with additional isolates from asymptomatic subjects.

Genomic Diversification, Structural Plasticity, and Hybridization in Leishmania (Viannia) braziliensis

“…Our final strategy to evaluate genomic variability among L. braziliensis genomes involved analysis of nucleotide-level variations (SNPs). Comparing the number of SNPs found in this study (42,617 to 435,529; n = 21) ( Supplementary Table S3) and the recent report in L. braziliensis isolates from Peru (Broeck et al, 2020), with the number of variants described in other Old/ New World Leishmania species, such as L. donovani (3,549 SNPs; n = 17) (Downing et al, 2011); L. infantum (17,333 SNPs; n = 12) (Rogers et al, 2014) (~3,000 SNPs; n = 20) (Teixeira et al, 2017), L. amazonensis/L. mexicana vs. L. infantum (~21,000 SNPs; n = 2) (Valdivia et al, 2017), L. panamensis; (~62,000 SNPs; n = 22) (Patino et al, 2020), L. amazonensis vs. reference genome of L. mexicana (~40,000 SNPs) (Patino et al, 2019b) and L. peruviana vs. reference genome of L. braziliensis (~112,000 SNPs; n = 2) (Valdivia et al, 2015), we can confirm that L. braziliensis, is the Leishmania (Viannia) species with the highest genetic variability circulating in some regions of South America (Brazil, Colombia and Peru).…”

Trans-Atlantic Spillover: Deconstructing the Ecological Adaptation of Leishmania infantum in the Americas

“…To detect this variability, neotropical L. infantum genomic diversity has been recently explored by deep sequencing approaches. Teixeira et al [60] performed a comparative analysis of whole genome sequences of twenty L. infantum isolates from humans and dogs in northeastern Brazil. Despite high sequence identity, individual differences displayed sufficient variation to allow the isolates to be clustered based on the primary sequence.…”

Trans-Atlantic Spill Over: Deconstructing the Ecological Adaptation of Leishmania Infantum in the Americas

“…To detect this variability, Neotropical L. infantum genomic diversity has been recently explored by deep sequencing approaches. Teixeira et al, (2017) [59] performed a comparative analysis of whole genome sequences of twenty L. infantum isolates from human and dogs in northeastern Brazil. Despite high sequence identity, individual differences displayed sufficient variation to allow the isolates to be clustered based on the primary sequence.…”