Genome Analysis of Endotrypanum and Porcisia spp., Closest Phylogenetic Relatives of Leishmania, Highlights the Role of Amastins in Shaping Pathogenicity

Abstract

While numerous genomes of Leishmania spp. have been sequenced and analyzed, an understanding of the evolutionary history of these organisms remains limited due to the unavailability of the sequence data for their closest known relatives, Endotrypanum and Porcisia spp., infecting sloths and porcupines. We have sequenced and analyzed genomes of three members of this clade in order to fill this gap. Their comparative analyses revealed only minute differences from Leishmaniamajor genome in terms of metabolic capacities. We also documented that the number of genes under positive selection on the Endotrypanum/Porcisia branch is rather small, with the flagellum-related group of genes being over-represented. Most significantly, the analysis of gene family evolution revealed a substantially reduced repertoire of surface proteins, such as amastins and biopterin transporters BT1 in the Endotrypanum/Porcisia species when compared to amastigote-dwelling Leishmania. This reduction was especially pronounced for δ-amastins, a subfamily of cell surface proteins crucial in the propagation of Leishmania amastigotes inside vertebrate macrophages and, apparently, dispensable for Endotrypanum/Porcisia, which do not infect such cells.

Chromosome-scale genome sequencing, assembly and annotation of six genomes from subfamily Leishmaniinae

“…Prior to the release of our genome, there were no genome sequences for genus Porcisia . Subsequently, the partial genome of P. deanei was released and published 15 .…”

Genomics of Trypanosomatidae: Where We Stand and What Needs to Be Done?

“…Endotrypanum monterogeii and Porcisia spp., being dixenous parasites of sloths and porcupines, respectively, represent the closest known relatives of Leishmania. The recently published analysis of their genomic sequences shed light on the evolution of pathogenicity in dixenous Leishmaniinae, which appears to be shaped mainly by changes in the amastin repertoire [ 78 ].…”

“…Some examples are provided below. The analysis of amastins, a large family of surface glycoproteins expressed primarily in amastigotes, revealed that δ-amastin subfamily is restricted to the dixenous Leishmaniinae and its expansion has likely happened in the ancestor of the genus Leishmania [ 78 , 125 ]. The repertoire of adenylate cyclases has expanded in dixenous trypanosomatids and many genes encoding these proteins pseudogenized in those subspecies of T. brucei , which lost the ability to develop in insects [ 126 ].…”

Chromosome-Scale Assembly of the Complete Genome Sequence of Porcisia hertigi, Isolate C119, Strain LV43

“…Initially classified as Leishmania hertigi , subsequent phylogenetic studies resulted in its reclassification into a new genus, Porcisia ( 3 ), within the subfamily Leishmaniinae ( 4 ). To date, only a partial assembly of Porcisia deanei ( 5 ) (strain TCC258) is available within this genus. We now assemble the complete genome sequence of Porcisia hertigi , strain LV43, isolate C119 (WHO code MCOE/PA/1965/C119;LV43), isolated from a porcupine in Panama in 1965.…”