Next Article in Journal
Investigation of DNA Damage and Cell-Cycle Distribution in Human Peripheral Blood Lymphocytes under Exposure to High Doses of Proton Radiotherapy
Next Article in Special Issue
Proteolytic Cleavages in the VEGF Family: Generating Diversity among Angiogenic VEGFs, Essential for the Activation of Lymphangiogenic VEGFs
Previous Article in Journal
Expression of Semaphorin 3A in Malignant and Normal Bladder Tissue: Immunohistochemistry Staining and Morphometric Evaluation
Previous Article in Special Issue
Unravelling the Network of Nuclear Matrix Metalloproteinases for Targeted Drug Design
Article

Evolutionary Analysis of Cystatins of Early-Emerging Metazoans Reveals a Novel Subtype in Parasitic Cnidarians

1
Biology Centre, Institute of Parasitology, Czech Academy of Sciences, 37005 České Budějovice, Czech Republic
2
Faculty of Science, University of South Bohemia, 37005 České Budějovice, Czech Republic
3
Department of Life Sciences, Natural History Museum, London SW7 5BD, UK
4
Department of Microbiology, Oregon State University, Corvallis, OR 97331, USA
5
Fish Pathology Group, Instituto de Acuicultura Torre de la Sal (IATS-CSIC), 12595 Castellón, Spain
6
Scottish Fish Immunology Research Centre, Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen AB24 3UU, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Hang Fai Kwok
Biology 2021, 10(2), 110; https://doi.org/10.3390/biology10020110
Received: 30 December 2020 / Revised: 26 January 2021 / Accepted: 31 January 2021 / Published: 3 February 2021
Cysteine protease inhibitors (cystatins) are molecules that play key protective roles in protein degradation and are involved in the immunomodulation of host responses to parasites. Little is known about the cystatin gene repertoire, evolution, and lineage-specific adaptations of early-emerging metazoans. Using bioinformatics searches, we identified orthologues of cystatins in basal animal lineages including free-living and parasite taxa. We aimed to explore whether their cystatin gene repertoire and evolution follow similar patterns recognized for derived metazoans and whether the modifications are linked to the organism’s life history. We revealed that cysteine protease inhibitors from early-emerging animal groups are highly diverse, with modifications in gene organization and protein architecture. A new subtype of cystatins was discovered in the parasitic cnidarians, the Myxozoa, which has so far been only reported for a group of derived animals: trematode flukes. We set out hypotheses to describe the driving forces for the origins of this unique cystatin subtype and propose evolutionary scenarios elucidating the current existence of cystatins in the Metazoa, especially in their early-emerging lineages. Our research identified molecules for which future functional studies may help to identify their roles in host–parasite interactions and for the parasite itself.
The evolutionary aspects of cystatins are greatly underexplored in early-emerging metazoans. Thus, we surveyed the gene organization, protein architecture, and phylogeny of cystatin homologues mined from 110 genomes and the transcriptomes of 58 basal metazoan species, encompassing free-living and parasite taxa of Porifera, Placozoa, Cnidaria (including Myxozoa), and Ctenophora. We found that the cystatin gene repertoire significantly differs among phyla, with stefins present in most of the investigated lineages but with type 2 cystatins missing in several basal metazoan groups. Similar to liver and intestinal flukes, myxozoan parasites possess atypical stefins with chimeric structure that combine motifs of classical stefins and type 2 cystatins. Other early metazoan taxa regardless of lifestyle have only the classical representation of cystatins and lack multi-domain ones. Our comprehensive phylogenetic analyses revealed that stefins and type 2 cystatins clustered into taxonomically defined clades with multiple independent paralogous groups, which probably arose due to gene duplications. The stefin clade split between the subclades of classical stefins and the atypical stefins of myxozoans and flukes. Atypical stefins represent key evolutionary innovations of the two parasite groups for which their origin might have been linked with ancestral gene chimerization, obligate parasitism, life cycle complexity, genome reduction, and host immunity. View Full-Text
Keywords: cysteine protease inhibitor; stefin; signal peptide; parasite; phylogenetic analysis; diversification; protein structure cysteine protease inhibitor; stefin; signal peptide; parasite; phylogenetic analysis; diversification; protein structure
Show Figures

Graphical abstract

MDPI and ACS Style

Bartošová-Sojková, P.; Kyslík, J.; Alama-Bermejo, G.; Hartigan, A.; Atkinson, S.D.; Bartholomew, J.L.; Picard-Sánchez, A.; Palenzuela, O.; Faber, M.N.; Holland, J.W.; Holzer, A.S. Evolutionary Analysis of Cystatins of Early-Emerging Metazoans Reveals a Novel Subtype in Parasitic Cnidarians. Biology 2021, 10, 110. https://doi.org/10.3390/biology10020110

AMA Style

Bartošová-Sojková P, Kyslík J, Alama-Bermejo G, Hartigan A, Atkinson SD, Bartholomew JL, Picard-Sánchez A, Palenzuela O, Faber MN, Holland JW, Holzer AS. Evolutionary Analysis of Cystatins of Early-Emerging Metazoans Reveals a Novel Subtype in Parasitic Cnidarians. Biology. 2021; 10(2):110. https://doi.org/10.3390/biology10020110

Chicago/Turabian Style

Bartošová-Sojková, Pavla, Jiří Kyslík, Gema Alama-Bermejo, Ashlie Hartigan, Stephen D. Atkinson, Jerri L. Bartholomew, Amparo Picard-Sánchez, Oswaldo Palenzuela, Marc N. Faber, Jason W. Holland, and Astrid S. Holzer. 2021. "Evolutionary Analysis of Cystatins of Early-Emerging Metazoans Reveals a Novel Subtype in Parasitic Cnidarians" Biology 10, no. 2: 110. https://doi.org/10.3390/biology10020110

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop