Private Selective Sweeps Identified from Next-Generation Pool-Sequencing Reveal Convergent Pathways under Selection in Two Inbred Schistosoma mansoni Strains

Abstract

Background

The trematode flatworms of the genus Schistosoma, the causative agents of schistosomiasis, are among the most prevalent parasites in humans, affecting more than 200 million people worldwide. In this study, we focused on two well-characterized strains of S. mansoni, to explore signatures of selection. Both strains are highly inbred and exhibit differences in life history traits, in particular in their compatibility with the intermediate host Biomphalaria glabrata.

Methodology/Principal Findings

We performed high throughput sequencing of DNA from pools of individuals of each strain using Illumina technology and identified single nucleotide polymorphisms (SNP) and copy number variations (CNV). In total, 708,898 SNPs were identified and roughly 2,000 CNVs. The SNPs revealed low nucleotide diversity (π = 2×10 ⁻⁴) within each strain and a high differentiation level (Fst = 0.73) between them. Based on a recently developed in-silico approach, we further detected 12 and 19 private ( i.e. specific non-overlapping) selective sweeps among the 121 and 151 sweeps found in total for each strain.

Conclusions/Significance

Functional annotation of transcripts lying in the private selective sweeps revealed specific selection for functions related to parasitic interaction ( e.g. cell-cell adhesion or redox reactions). Despite high differentiation between strains, we identified evolutionary convergence of genes related to proteolysis, known as a key virulence factor and a potential target of drug and vaccine development. Our data show that pool-sequencing can be used for the detection of selective sweeps in parasite populations and enables one to identify biological functions under selection.

Author Summary

Adaptation of parasites to their environment is governed by the principle of selection. Favourable mutations are fixed in populations while deleterious mutations are progressively eliminated. Here, we aimed to find signatures of selection in two strains of Schistosoma mansoni, the causative agent of intestinal schistosomiasis. The strains differ in specific characters, in particular in their capacity to infect intermediate host snails. The reason for this is unknown and understanding it could help control the spreading of the disease. Finding footprints of adaptation to different snail hosts would lead to the discovery of genes that are particularly important for the interaction. Since a single parasite does not contain sufficient DNA to be sequenced, we pooled several individuals, sequenced them as a whole analysed them. In the regions under selection we found genes that are indeed linked to the parasitic lifestyle. We also discovered that natural selection led to diversification of genes that are related to proteolysis, the process by which the parasite destroys host tissue. The related proteins are considered good targets for drug development and vaccination. Our results suggest that in natural populations many variants of these genes exist and that they evolve rapidly, which might hamper therapeutic approaches.