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. 2019 Nov 21;13(11):e0007846.
doi: 10.1371/journal.pntd.0007846. eCollection 2019 Nov.

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

Lian Xu  1   2   3 , Meng Xu  4 , Xi Sun  1   2   3 , Junyang Xu  4 , Xin Zeng  1   2   3 , Dai Shan  4 , Dongjuan Yuan  1   2   3 , Ping He  1   2   3 , Weiming He  4 , Yulan Yang  4 , Shiqi Luo  1   2   3 , Jie Wei  1   2   3 , Xiaoying Wu  2 , Zhen Liu  1   2   3 , Xiaomin Xu  4 , Zhensheng Dong  4 , Langui Song  1   2   3 , Beibei Zhang  1   2   3 , Zilong Yu  1   2   3 , Lifu Wang  1   2   3 , Chi Zhang  4 , Xiaodong Fang  4 , Qiang Gao  4 , Zhiyue Lv  1   2 , Zhongdao Wu  1   2
Affiliations

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

Lian Xu et al. PLoS Negl Trop Dis. .

Abstract

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. The complex life cycle of A. cantonensis.
The complete life cycle of A. cantonensis requires two different hosts (snail and rat): L1 larvae are excreted in the feces of a definitive host (rat). When ingested by an intermediate host, they develop into infective L3 after molting twice and are maintained at that stage until they are eaten by a definitive host. The L3 are ingested by a rat and invade intestinal tissue and then migrate to the central nervous system (CNS), where they molt twice and develop into L5. Finally, these worms leave the brain and then reach the pulmonary arteries, where they become fully mature adults. Human infections are acquired by eating undercooked snails, paratenic hosts such as frogs, or contaminated vegetables containing L3 of A. cantonensis. Since humans are non-permissive hosts of A. cantonensis, the larvae reach to the brain and cause eosinophilic meningitis.
Fig 2
Fig 2. RTE-RTE retrotransposons expansion in A. cantonensis.
(a), The genomic portion of the RTE-RTEs in eight nematodes (three of which lack RTE-RTEs using the same criterion) at different given divergence generated by the de novo prediction. The divergence is adjusted for multiple substitutions using the Jukes-Cantor distance. (b), The phylogenetic tree depicting the relationship of RTE-RTEs among five nematodes. The branches of five species of nematodes are colored in blue for A.suum, red for A. cantonensis, light blue for C. elegans, orange for H.contorus and green for N. americanus.
Fig 3
Fig 3. Phylogenomic analysis of EC-SOD in different species of nematodes and flatworms.
(a), Phylogenic tree depicts a cladogram of eight nematodes and six flatworms profiled in this study. Number at the node indicates ASTRAL supporting value while the branches with the sketch of snails represents intermediate hosts. Specifically, the number of ʺ+ʺ shows the increasing spectrum of suitable intermediate hosts. (b), Maximum likelihood tree of EC-SODs in 14 species and the mRNA expression patterns of A. cantonensis’s EC-SODs. GBH: the EC-SOD clustered in gastropod-borne helminths. (c), The multiple sequence alignment of EC-SODs from sequences in Fig 3b. (d), Convergent study at amino acids levels in the EC-SODs from gastropod-borne helminths at an extended background of 62 species. The x-axis shows multiple sequence alignment position in Fig 3c.
Fig 4
Fig 4. Phylogenomic analysis of three proteases related to hemoglobin digestion in eight nematodes.
(a), H&E stained longitudinal section of the digestive tract from a female adult (on the upper left) shows the presence of red blood cells. The possible hemoglobin digestion pathway in the nematodes is illustrated on the right panel [65] with subfamily of enzymes (aspartic protease, cysteine protease and metalloprotease) related to hemoglobin and/or tissue digestion highlighted in yellow background. Specifically, the expanded subfamilies of enzymes from A. cantonensis are highlighted in red. Maximum likelihood phylogenies of necepsin-1 (b), Lgmn (c) and Nep-1(d) show expansion of these proteases in A. cantonensis, N. americanus and/or H. contortus, all of which are blood-feeding nematodes.
Fig 5
Fig 5. Evolution of astacin-like genes and expression pattern across in the life-cycles of A. cantonensis.
(a), Phylogenetic analysis of the astacin-like genes containing the astacin domain (PF01400). We named the purple cluster MTP-1 because it shows the best hit with MTP-1 in the MEROPS database. (b), Expression patterns of expanded sub-clade I astacin-like genes in A. cantonensis. The genes in sub-clade I are upregulated in L1 or L3, which are two stages of invasion into intermediate host or mammalian hosts. c, mRNA expression pattern of expanded sub-clade II astacin-like genes in A. cantonensis.
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Publication types

Grants and funding

ZD-W received grants from National Research and Development Plan of China (2016YFC1200500), the Major Basic Research of Ministry of Science and Technology of China (973 Project) (No.2010CB530000), National Natural Science Foundation of China (No.81261160324, No.81271855, and No.81371836), Science and Technology Planning Project of Guangdong Province (No.2016A050502008), Natural Science Foundation of Guangdong Province, China (No. 2015A030310058) and the 111 Project (Grant No. B12003). ZY-L received a grant from National Natural Science Foundation of China (No. 81572023) and Science and Technology Planning Project of Guangdong Province (2019B030316025). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.