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Analysis of Schistosoma mansoni genes shared with Deuterostomia and with possible roles in host interactions.

Venancio TM, DeMarco R, Almeida GT, Oliveira KC, Setubal JC, Verjovski-Almeida S - BMC Genomics (2007)

Bottom Line: In this work we found 427 genes conserved in the Deuterostomia group that have orthologs in S. mansoni and no members in any nematodes and insects so far sequenced.Using S. mansoni homologs, we have employed a parsimonious rationale to compute the total gene losses/gains in nematodes, arthropods and deuterostomes under either the Coelomata or the Ecdysozoa evolutionary hypotheses; our results show a lower losses/gains number under the latter hypothesis.Given their known functions in Deuterostomia, it is possible that some of them have been co-opted to perform functions related (directly or indirectly) to host adaptation or interaction with host signaling processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Bioinformatics; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil. venancio@iq.usp.br

ABSTRACT

Background: Schistosoma mansoni is a blood helminth parasite that causes schistosomiasis, a disease that affects 200 million people in the world. Many orthologs of known mammalian genes have been discovered in this parasite and evidence is accumulating that some of these genes encode proteins linked to signaling pathways in the parasite that appear to be involved with growth or development, suggesting a complex co-evolutionary process.

Results: In this work we found 427 genes conserved in the Deuterostomia group that have orthologs in S. mansoni and no members in any nematodes and insects so far sequenced. Among these genes we have identified Insulin Induced Gene (INSIG), Interferon Regulatory Factor (IRF) and vasohibin orthologs, known to be involved in mammals in mevalonate metabolism, immune response and angiogenesis control, respectively. We have chosen these three genes for a more detailed characterization, which included extension of their cloned messages to obtain full-length sequences. Interestingly, SmINSIG showed a 10-fold higher expression in adult females as opposed to males, in accordance with its possible role in regulating egg production. SmIRF has a DNA binding domain, a tryptophan-rich N-terminal region and several predicted phosphorylation sites, usually important for IRF activity. Fourteen different alternatively spliced forms of the S. mansoni vasohibin (SmVASL) gene were detected that encode seven different protein isoforms including one with a complete C-terminal end, and other isoforms with shorter C-terminal portions. Using S. mansoni homologs, we have employed a parsimonious rationale to compute the total gene losses/gains in nematodes, arthropods and deuterostomes under either the Coelomata or the Ecdysozoa evolutionary hypotheses; our results show a lower losses/gains number under the latter hypothesis.

Conclusion: The genes discussed which are conserved between S. mansoni and deuterostomes, probably have an ancient origin and were lost in Ecdysozoa, being still present in Lophotrochozoa. Given their known functions in Deuterostomia, it is possible that some of them have been co-opted to perform functions related (directly or indirectly) to host adaptation or interaction with host signaling processes.

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S. mansoni Vasohibin orthologs and expression along the life cycle. A: Multiple sequence alignment of SmVASLv6a (the longer isoform) and several orthologs. B: Maximum Likelihood tree constructed from the alignment of SmVASLv6a and other vasohibins found in public databases. The S. mansoni branch is represented in red. Numbers next to the branches represent bootstrap values (in 1000 samplings). C: Real time RT-PCR using total RNA samples from egg, miracidium, cercaria, schistosomulum or adult and primers for SmVASL. Relative fold change was calculated by comparing the Ct value for each sample to Ct values for alpha-tubulin (internal standard).
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Figure 5: S. mansoni Vasohibin orthologs and expression along the life cycle. A: Multiple sequence alignment of SmVASLv6a (the longer isoform) and several orthologs. B: Maximum Likelihood tree constructed from the alignment of SmVASLv6a and other vasohibins found in public databases. The S. mansoni branch is represented in red. Numbers next to the branches represent bootstrap values (in 1000 samplings). C: Real time RT-PCR using total RNA samples from egg, miracidium, cercaria, schistosomulum or adult and primers for SmVASL. Relative fold change was calculated by comparing the Ct value for each sample to Ct values for alpha-tubulin (internal standard).

Mentions: We have identified seven different polypeptides that are encoded by these variants, representing different deduced protein isoforms (Figure 4A). As noted earlier, isoforms SmVASLv3, 4, 5, 8, 9 and 11 encode the same 57 amino acid protein. Due to the absence of a stop codon in the SmVASLv6 sequence in the segment amplified by RT-PCR, a 3'-RACE experiment was conducted to extend SmVASLv6 sequence, which resulted in two additional longer SmVASLv6 isoforms, SmVASLv6a and SmVASLv6b. The longer isoform, SmVASLv6a encodes a 337 amino acid protein, the longest protein isoform detected here. When compared through BLASTP with the Swiss-Prot/TrEMBL database, the highest match was a protein of S. japonicum of unknown function ([Swissprot: Q5DB91]). The second best match was to human vasohibin-like protein (vasohibin 2, [Swissprot: Q86V25]) (Figure 4B) to which SmVASLv6a protein aligns with 37% identity and 57% similarity over 252 amino acids (71% coverage of the human protein). Alignment of SmVASLv6a and human vasohibin 2 reveals a C-terminal divergence between these two proteins (Figure 4B). 5'-RACE experiments under several conditions were performed, without success. A multiple sequence alignment and a phylogenetic tree of SmVASLv6a and several other orthologs are represented in Figure 5A and 5B, respectively.


Analysis of Schistosoma mansoni genes shared with Deuterostomia and with possible roles in host interactions.

Venancio TM, DeMarco R, Almeida GT, Oliveira KC, Setubal JC, Verjovski-Almeida S - BMC Genomics (2007)

S. mansoni Vasohibin orthologs and expression along the life cycle. A: Multiple sequence alignment of SmVASLv6a (the longer isoform) and several orthologs. B: Maximum Likelihood tree constructed from the alignment of SmVASLv6a and other vasohibins found in public databases. The S. mansoni branch is represented in red. Numbers next to the branches represent bootstrap values (in 1000 samplings). C: Real time RT-PCR using total RNA samples from egg, miracidium, cercaria, schistosomulum or adult and primers for SmVASL. Relative fold change was calculated by comparing the Ct value for each sample to Ct values for alpha-tubulin (internal standard).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2194728&req=5

Figure 5: S. mansoni Vasohibin orthologs and expression along the life cycle. A: Multiple sequence alignment of SmVASLv6a (the longer isoform) and several orthologs. B: Maximum Likelihood tree constructed from the alignment of SmVASLv6a and other vasohibins found in public databases. The S. mansoni branch is represented in red. Numbers next to the branches represent bootstrap values (in 1000 samplings). C: Real time RT-PCR using total RNA samples from egg, miracidium, cercaria, schistosomulum or adult and primers for SmVASL. Relative fold change was calculated by comparing the Ct value for each sample to Ct values for alpha-tubulin (internal standard).
Mentions: We have identified seven different polypeptides that are encoded by these variants, representing different deduced protein isoforms (Figure 4A). As noted earlier, isoforms SmVASLv3, 4, 5, 8, 9 and 11 encode the same 57 amino acid protein. Due to the absence of a stop codon in the SmVASLv6 sequence in the segment amplified by RT-PCR, a 3'-RACE experiment was conducted to extend SmVASLv6 sequence, which resulted in two additional longer SmVASLv6 isoforms, SmVASLv6a and SmVASLv6b. The longer isoform, SmVASLv6a encodes a 337 amino acid protein, the longest protein isoform detected here. When compared through BLASTP with the Swiss-Prot/TrEMBL database, the highest match was a protein of S. japonicum of unknown function ([Swissprot: Q5DB91]). The second best match was to human vasohibin-like protein (vasohibin 2, [Swissprot: Q86V25]) (Figure 4B) to which SmVASLv6a protein aligns with 37% identity and 57% similarity over 252 amino acids (71% coverage of the human protein). Alignment of SmVASLv6a and human vasohibin 2 reveals a C-terminal divergence between these two proteins (Figure 4B). 5'-RACE experiments under several conditions were performed, without success. A multiple sequence alignment and a phylogenetic tree of SmVASLv6a and several other orthologs are represented in Figure 5A and 5B, respectively.

Bottom Line: In this work we found 427 genes conserved in the Deuterostomia group that have orthologs in S. mansoni and no members in any nematodes and insects so far sequenced.Using S. mansoni homologs, we have employed a parsimonious rationale to compute the total gene losses/gains in nematodes, arthropods and deuterostomes under either the Coelomata or the Ecdysozoa evolutionary hypotheses; our results show a lower losses/gains number under the latter hypothesis.Given their known functions in Deuterostomia, it is possible that some of them have been co-opted to perform functions related (directly or indirectly) to host adaptation or interaction with host signaling processes.

View Article: PubMed Central - HTML - PubMed

Affiliation: Laboratory of Bioinformatics; Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, 05508-900 São Paulo, SP, Brazil. venancio@iq.usp.br

ABSTRACT

Background: Schistosoma mansoni is a blood helminth parasite that causes schistosomiasis, a disease that affects 200 million people in the world. Many orthologs of known mammalian genes have been discovered in this parasite and evidence is accumulating that some of these genes encode proteins linked to signaling pathways in the parasite that appear to be involved with growth or development, suggesting a complex co-evolutionary process.

Results: In this work we found 427 genes conserved in the Deuterostomia group that have orthologs in S. mansoni and no members in any nematodes and insects so far sequenced. Among these genes we have identified Insulin Induced Gene (INSIG), Interferon Regulatory Factor (IRF) and vasohibin orthologs, known to be involved in mammals in mevalonate metabolism, immune response and angiogenesis control, respectively. We have chosen these three genes for a more detailed characterization, which included extension of their cloned messages to obtain full-length sequences. Interestingly, SmINSIG showed a 10-fold higher expression in adult females as opposed to males, in accordance with its possible role in regulating egg production. SmIRF has a DNA binding domain, a tryptophan-rich N-terminal region and several predicted phosphorylation sites, usually important for IRF activity. Fourteen different alternatively spliced forms of the S. mansoni vasohibin (SmVASL) gene were detected that encode seven different protein isoforms including one with a complete C-terminal end, and other isoforms with shorter C-terminal portions. Using S. mansoni homologs, we have employed a parsimonious rationale to compute the total gene losses/gains in nematodes, arthropods and deuterostomes under either the Coelomata or the Ecdysozoa evolutionary hypotheses; our results show a lower losses/gains number under the latter hypothesis.

Conclusion: The genes discussed which are conserved between S. mansoni and deuterostomes, probably have an ancient origin and were lost in Ecdysozoa, being still present in Lophotrochozoa. Given their known functions in Deuterostomia, it is possible that some of them have been co-opted to perform functions related (directly or indirectly) to host adaptation or interaction with host signaling processes.

Show MeSH
Related in: MedlinePlus