Whole-genomic comparison reveals complex population dynamics and parasitic adaptation of Echinococcus granulosus...

Cystic echinococcosis (CE), caused by Echinococcus granulosus sensu stricto (s.s.), poses a substantial risk to both humans and domestic animals globally. Here, we compared the whole genomes of 111 E. granulosus s.s. samples from China. Genomic variation data revealed frequent cross-fertilization in the hermaphroditic E. granulosus. The G1 and G3 genotypes represent distinct mitochondrial lineages, while showing no differentiation in the nuclear genome, suggesting mito-nuclear discordance caused by historical geographic separation and subsequent fusion. Population structure, demographic history, and gene flow among populations reflected the transmission route of E. granulosus s.s. from the Middle East to Qinghai-Xizang Plateau through the migration of nomadic people, followed by introgression during secondary contact. Genomic variations highlighted selection signatures within the genome prone to balancing selection, particularly impacting genes encoding membrane-related proteins, representing a potential evolutionary strategy for adaptation to parasitic life. Balancing selection pressure on the gene-coding sodium/bile acid cotransporter led to its high level of genetic stability, which may play a crucial role in the survival and development of E. granulosus during the parasitic stage, making it a potential drug target for the treatment of CE. Meanwhile, other genomic regions under strong balancing selection may provide potential targets for protective immunity. These findings offer valuable insights into the complex dynamics and adaptive evolution of E. granulosus s.s. in China.IMPORTANCEEchinococcus granulosus sensu stricto (s.s.) is the primary cause of cystic echinococcosis (CE), a parasitic disease affecting humans and livestock with significant health and economic impacts. Previous studies on this parasite relied on mitochondrial DNA to classify its genotypes and understand its genetic diversity. However, these studies cannot capture the full complexity of its evolutionary dynamics and adaptation strategies. Our research employs comprehensive genome-wide sequencing, offering a more nuanced view of its genetic landscape. We discovered that cross-fertilization appears to be a prevalent reproductive strategy in the hermaphroditic E. granulosus, underpinning the observed deep mitochondrial divergence between genotypes G1 and G3, as well as gene flow among populations. The transmission history of E. granulosus s.s. in China and its widespread genetic mixing were likely facilitated by the migrations of nomadic peoples. Furthermore, we identified genes under balancing selection, including the gene involved in the uptake of host bile acids, which play a crucial role in the parasite's survival and development, potentially offering new targets for intervention. Our research advances the understanding of the genetic diversity and evolutionary strategies of E. granulosus, laying the foundation for improved control measures of CE.