The Schistosoma mansoni phylome: using evolutionary genomics to gain insight into a parasite’s biology

Abstract

BackgroundSchistosoma mansoni is one of the causative agents of schistosomiasis, a neglected tropical disease that affects about 237 million people worldwide. Despite recent efforts, we still lack a general understanding of the relevant host-parasite interactions, and the possible treatments are limited by the emergence of resistant strains and the absence of a vaccine. The S. mansoni genome was completely sequenced and still under continuous annotation. Nevertheless, more than 45% of the encoded proteins remain without experimental characterization or even functional prediction. To improve our knowledge regarding the biology of this parasite, we conducted a proteome-wide evolutionary analysis to provide a broad view of the S. mansoni’s proteome evolution and to improve its functional annotation.ResultsUsing a phylogenomic approach, we reconstructed the S. mansoni phylome, which comprises the evolutionary histories of all parasite proteins and their homologs across 12 other organisms. The analysis of a total of 7,964 phylogenies allowed a deeper understanding of genomic complexity and evolutionary adaptations to a parasitic lifestyle. In particular, the identification of lineage-specific gene duplications pointed to the diversification of several protein families that are relevant for host-parasite interaction, including proteases, tetraspanins, fucosyltransferases, venom allergen-like proteins, and tegumental-allergen-like proteins. In addition to the evolutionary knowledge, the phylome data enabled us to automatically re-annotate 3,451 proteins through a phylogenetic-based approach rather than solely sequence similarity searches. To allow further exploitation of this valuable data, all information has been made available at PhylomeDB (http://www.phylomedb.org).ConclusionsIn this study, we used an evolutionary approach to assess S. mansoni parasite biology, improve genome/proteome functional annotation, and provide insights into host-parasite interactions. Taking advantage of a proteome-wide perspective rather than focusing on individual proteins, we identified that this parasite has experienced specific gene duplication events, particularly affecting genes that are potentially related to the parasitic lifestyle. These innovations may be related to the mechanisms that protect S. mansoni against host immune responses being important adaptations for the parasite survival in a potentially hostile environment. Continuing this work, a comparative analysis involving genomic, transcriptomic, and proteomic data from other helminth parasites, other parasites, and vectors will supply more information regarding parasite’s biology as well as host-parasite interactions.

In Silico Analysis of the Fucosylation-Associated Genome of the Human Blood Fluke Schistosoma mansoni: Cloning and Characterization of the Fucosyltransferase Multigene Family

“…Indeed, Silva et al [72], using a phylogenomic approach to identify lineage-specific gene duplications, concluded that expansion of the FucT gene family was among the most significant to have occurred in S. mansoni . In general, the downstream consequences for duplicated genes include nonfunctionalization (collection of degenerative mutations), neofunctionalization (attainment of a new function), and subfunctionalization (partitioning of the original function between duplicate genes) (reviewed by Hurles [73]).…”

“…Our search yielded 15 complete genes, including seven α3-FucTs, six α6-FucTs and two protein O-FucTs. Why schistosomes encode such a large number of FucT homologs remains unclear, however it is thought that such duplicative expansions are an adaptive response to the parasitic lifestyle and imply important roles for these genes in schistosome development and immunobiology [72]. Notably, this level of redundancy also exists in the non-parasitic nematode Caenorhabditis (see Figure 5; Table S5), which Oriol et al [36] attributes to the evolutionary selection of fucosylation over sialylation as a means of terminating glycosylation.…”

Inferences on the biochemical and environmental regulation of universal stress proteins from Schistosomiasis parasites

“…We used a visual analytics approach to integrate these data types and to identify orthologous pairs of protein sequences with a protein length of 184 aa USP in S. mansoni (Smp_076400) and S. japonicum (Locus Tag: Sjp_0058490; UniProt ID: Q86DW2). Gene synteny, obtained from SchistoDB49 and evolutionary genomics analysis called the S. mansoni phylome,63 indicated that an ortholog (Sha_107834) is encoded in the S. haematobium genome. Thus, the genomes of the three major human schistosomiasis parasites encode the 184 aa USP.…”

Gaining biological perspectives from schistosome genomes

“…Phylogenomics has been applied to schistosomes so as to place their proteomes into a broad evolutionary context with other parasitic and reference species as a novel approach to better understand their biology, particularly their interactions with their hosts [23]. Using this broad approach, insights into a wide range of features associated with host-parasite interactions were obtained with the primary aim of discovering new vaccine or drug targets.…”