Genomic analysis of Echinococcus granulosus sensu stricto: genetic diversity and population structure

Background: Cystic echinococcosis, caused by the tapeworm Echinococcus granulosus sensu stricto (ss), is a globally distributed, zoonotic disease that is recognised by WHO as a neglected tropical disease. Despite its clinical and economic importance, nuclear genomic variation in this parasite has not been systematically characterised across global populations. In this study, we aimed to characterise the genome-wide nuclear genetic diversity and population structure of E granulosus ss across globally distributed populations. Methods: We conducted a genomic study of 137 E granulosus ss samples from endemic regions across five continents, derived from previously collected parasite material from livestock, wildlife, and human infections. Using a chromosome-scale reference genome, we applied population genomic approaches to investigate genome-wide nuclear genetic diversity, population structure, and patterns of evolutionary constraint. Findings: We identified 1 071 085 nuclear single-nucleotide polymorphisms across 137 samples, with heterozygosity ranging from 46% to 93% per sample. Genome-wide analyses identified two major clades associated with geographical origin. Distinct regions of genetic differentiation were observed, particularly on chromosome 9. Conserved genes under purifying selection included those involved in glycan biosynthesis and core cellular functions, whereas variable genes were enriched in pathways such as ribosome biogenesis. Mitochondrial genotypes (G1 and G3) did not align with the nuclear genomic structure. Interpretation: To the best of our knowledge, this study provides the first broad atlas of nuclear genomic diversity in E granulosus ss, uncovering genetic diversity and population structure. The findings have important implications for molecular epidemiology, genomic surveillance, and translational development of diagnostics and vaccines. Incorporating genomic data into cystic echinococcosis control programmes could enhance WHO-aligned efforts to reduce the burden of this neglected tropical disease. Funding: Australian Research Council and the Estonian Ministry of Education and Research.