Whole-genome sequencing of Schistosoma mansoni reveals extensive diversity with limited selection despite mass drug administration

Abstract

Control and elimination of the parasitic disease schistosomiasis relies on mass administration of praziquantel. Whilst these programmes reduce infection prevalence and intensity, their impact on parasite transmission and evolution is poorly understood. Here we examine the genomic impact of repeated mass drug administration on Schistosoma mansoni populations with documented reduced praziquantel efficacy. We sequenced whole-genomes of 198 S. mansoni larvae from 34 Ugandan children from regions with contrasting praziquantel exposure. Parasites infecting children from Lake Victoria, a transmission hotspot, form a diverse panmictic population. A single round of treatment did not reduce this diversity with no apparent population contraction caused by long-term praziquantel use. We find evidence of positive selection acting on members of gene families previously implicated in praziquantel action, but detect no high frequency functionally impactful variants. As efforts to eliminate schistosomiasis intensify, our study provides a foundation for genomic surveillance of this major human parasite.

Genomic analysis of a parasite invasion: Colonization of the Americas by the blood fluke Schistosoma mansoni

“…Our data support previous work from whole genomes, mitochondrial genes and microsatellites suggesting that S. mansoni emerged in East Africa (Crellen et al, 2016;Morgan et al, 2005;Webster et al, 2013). In addition, our estimates of N e are within a range book-ended by other whole genome studies (Berger et al, 2021;Crellen et al, 2016).…”

“…K E Y W O R D S Africa, Brazil, codispersal, exome, human parasite, migration Adult schistosomes live in the blood vessels, making them difficult to sample. Genome and exome sequencing of schistosomes is now possible using whole genome amplification of miracidia larvae isolated from faeces or urine (Doyle et al, 2019;Le Clec'h et al, 2018;Shortt et al, 2017), and several genome-scale population analyses have recently been published (Berger et al, 2021;Platt et al, 2019;Shortt et al, 2017). Our goal here was to address the following questions with the available sequence data from both Africa (Niger, Senegal, Uganda, Tanzania) and the Americas (Caribbean, Brazil): (i) Are the genomic data consistent with a West African origin of colonizing schistosome populations?…”

Chromosome-level genome of Schistosoma haematobium underpins genome-wide explorations of molecular variation

“…The chromosome-level genome assembly for an Egyptian strain of S. haematobium adds important resources to the schistosome '-omics' reference toolkit. For example, this genome should accelerate large-scale population investigations and provide a unique opportunity to study the implications of genomic admixture, including its effect on biological and/or disease traits, morbidity and/or the effectiveness of control programs [51,52], including mass drug administration (MDA) [53]. The present resource should also enable future functional genomics investigations of S. haematobium [54][55][56] and facilitate investigations of the fundamental pathobiology of this important parasite using an integrative proteomic, glycomic and lipidomic approach.…”

Genomic landscape of drug response reveals novel mediators of anthelmintic resistance

“…However, some candidates are likely to have been falsely associated with resistance, as most studies present relatively weak genetic evidence from the analysis of single or few candidate loci in small numbers of helminth populations that often differ in both drug susceptibility and geographic origin. Many helminth species are exceptionally genetically diverse (23)(24)(25)(26), and consequently, candidate gene approaches have limited power to disentangle causal variation from linked but unrelated background genetic variation, a situation that is exacerbated by the experimental intractability and inadequate genomic resources available for many parasitic helminths (9).…”