The genetic basis of adaptive evolution in parasitic environment from the Angiostrongylus cantonensis genome

Author summary Angiostrongylus cantonensis, rat lungworm, is a common pathogen that causes human eosinophilic meningitis via eating contaminated food. Human angiostrongyliasis has been reported globally. This worm has a complex life-cycle, which includes an especially wide range of snails as intermediate hosts, making it more difficult to eradicate. In this study, we sequenced the genome and transcriptome, and performed comparative analyses to study the potential genetics of its biology using short-read and long-read sequencing technologies. We revealed some potential adaptive evolution in the genome, such as the expansion of retrotransposons and gene families encoding antioxidant enzymes, invasion, migration and digestion related proteases. Specifically, we found a potential clue suggesting convergent evolution of EC-SODs in Angiostrongylus and flukes, all of which require snails as intermediate hosts. These results provide an abundant data resource to study the biology and evolution of A. cantonensis and showed some potential targets against A. cantonensis and helminths with similar traits. Angiostrongylus cantonensis (rat lungworm) is the etiological agent of angiostrongyliasis, mainly causing eosinophilic meningitis or meningoencephalitis in human. Although the biology of A. cantonensis is relatively well known, little is understood about the mechanisms of the parasite's development and survival in definitive hosts, or its adaptation to a broad range of snail intermediate hosts. Here, we generate a high-quality assembly of a well-defined laboratory strain of A. cantonensis from Guangzhou, China, by using Illumina and PacBio sequencing technologies. We undertake comparative analyses with representative helminth genomes and explore transcriptomic data throughout key developmental life-cycles of the parasite. We find that part of retrotransposons and gene families undergo multiple waves of expansions. These include extracellular superoxide dismutase (EC-SOD) and astacin-like proteases which are considered to be associated with invasion and survival of the parasite. Furthermore, these paralogs from different sub-clades based on phylogeny, have different expression patterns in the molluscan and rodent stages, suggesting divergent functions under the different parasitic environment. We also find five candidate convergent signatures in the EC-SOD proteins from flukes and one sub-clade of A. cantonensis. Additionally, genes encoding proteolytic enzymes, involved in host hemoglobin digestion, exhibit expansion in A. cantonensis as well as two other blood-feeding nematodes. Overall, we find several potential adaptive evolutionary signatures in A. cantonensis, and also in some other helminths with similar traits. The genome and transcriptomes provide a useful resource for detailed studies of A. cantonensis-host adaptation and an in-depth understanding of the global-spread of angiostrongyliasis.