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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-like (SmVASL) isoforms. A: Schematic representation of SmVASL transcripts aligned to the S. mansoni genomic sequence. The thick gray bar at the top represents the genomic sequence of Supercontig_0000046. Coding sequences, UTRs and introns are represented by thick, thin and dashed lines, respectively. We have colored and numbered the different exons consecutively in an arbitrary way, in the order that each new exon splicing form appears in Figure 4A. Primers that were used for the RT-PCR amplification and RACE experiments of SmVASL alternatively spliced forms are represented by green and blue arrows, respectively. Deduced protein-coding ORFs of SmVASL message are represented by thick colored lines, and the lengths of the deduced encoded proteins are displayed at the right side of each splice variant. The asterisks next to SmVASLv6, SmVASLv6a and SmVASLv6b indicate that the latter two are the result of a 3'-RACE-PCR experiment (3'-RACE primers represented by blue arrows); B: Local alignment (BLAST) showing the conserved region of SmVASLv6a and human vasohibin 2; C: Agarose gel electrophoresis of RT-PCR products from a reaction performed with primers indicated in panel A with green arrows. RT indicates that cDNA was synthesized by Reverse Transcriptase with poly-dT priming using RNA as template, and PCR was subsequently performed. No RT indicates a negative control where PCR was performed with an RNA sample incubated with poly-dT but no reverse transcriptase, to control for the absence of genomic DNA contamination.
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Figure 4: S. mansoni Vasohibin-like (SmVASL) isoforms. A: Schematic representation of SmVASL transcripts aligned to the S. mansoni genomic sequence. The thick gray bar at the top represents the genomic sequence of Supercontig_0000046. Coding sequences, UTRs and introns are represented by thick, thin and dashed lines, respectively. We have colored and numbered the different exons consecutively in an arbitrary way, in the order that each new exon splicing form appears in Figure 4A. Primers that were used for the RT-PCR amplification and RACE experiments of SmVASL alternatively spliced forms are represented by green and blue arrows, respectively. Deduced protein-coding ORFs of SmVASL message are represented by thick colored lines, and the lengths of the deduced encoded proteins are displayed at the right side of each splice variant. The asterisks next to SmVASLv6, SmVASLv6a and SmVASLv6b indicate that the latter two are the result of a 3'-RACE-PCR experiment (3'-RACE primers represented by blue arrows); B: Local alignment (BLAST) showing the conserved region of SmVASLv6a and human vasohibin 2; C: Agarose gel electrophoresis of RT-PCR products from a reaction performed with primers indicated in panel A with green arrows. RT indicates that cDNA was synthesized by Reverse Transcriptase with poly-dT priming using RNA as template, and PCR was subsequently performed. No RT indicates a negative control where PCR was performed with an RNA sample incubated with poly-dT but no reverse transcriptase, to control for the absence of genomic DNA contamination.

Mentions: Vasohibins constitute a recently described family of endothelium-derived angiogenesis inhibitors in humans [35,36]. The presence of a Vasohibin ortholog in schistosomes might suggest a potential angiogenesis inhibition process in the host, mediated by schistosomes' molecules. Complete sequencing of clone MA3-9999U-M294-F04-U.B, the longest clone in SmAE cluster C605907.1, showed a transcript with 975 bases (Figure 4A) that we named SmVASL for S. mansoni Vasohibin-like gene. BLASTP comparison to Swiss-Prot/TrEMBL showed the best match (48% identity and 58% similarity over 90 amino acids) to vasohibin 2 ([Swissprot: Q86V25] or FLJ12505 protein), a recently described human vasohibin-like protein [36]. The amino portion of SmVASL deduced protein (starting at Leu4) did align to Leu142 of human vasohibin 2, thus suggesting that SmVASL represented a partial sequence of the S. mansoni ortholog.


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-like (SmVASL) isoforms. A: Schematic representation of SmVASL transcripts aligned to the S. mansoni genomic sequence. The thick gray bar at the top represents the genomic sequence of Supercontig_0000046. Coding sequences, UTRs and introns are represented by thick, thin and dashed lines, respectively. We have colored and numbered the different exons consecutively in an arbitrary way, in the order that each new exon splicing form appears in Figure 4A. Primers that were used for the RT-PCR amplification and RACE experiments of SmVASL alternatively spliced forms are represented by green and blue arrows, respectively. Deduced protein-coding ORFs of SmVASL message are represented by thick colored lines, and the lengths of the deduced encoded proteins are displayed at the right side of each splice variant. The asterisks next to SmVASLv6, SmVASLv6a and SmVASLv6b indicate that the latter two are the result of a 3'-RACE-PCR experiment (3'-RACE primers represented by blue arrows); B: Local alignment (BLAST) showing the conserved region of SmVASLv6a and human vasohibin 2; C: Agarose gel electrophoresis of RT-PCR products from a reaction performed with primers indicated in panel A with green arrows. RT indicates that cDNA was synthesized by Reverse Transcriptase with poly-dT priming using RNA as template, and PCR was subsequently performed. No RT indicates a negative control where PCR was performed with an RNA sample incubated with poly-dT but no reverse transcriptase, to control for the absence of genomic DNA contamination.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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Figure 4: S. mansoni Vasohibin-like (SmVASL) isoforms. A: Schematic representation of SmVASL transcripts aligned to the S. mansoni genomic sequence. The thick gray bar at the top represents the genomic sequence of Supercontig_0000046. Coding sequences, UTRs and introns are represented by thick, thin and dashed lines, respectively. We have colored and numbered the different exons consecutively in an arbitrary way, in the order that each new exon splicing form appears in Figure 4A. Primers that were used for the RT-PCR amplification and RACE experiments of SmVASL alternatively spliced forms are represented by green and blue arrows, respectively. Deduced protein-coding ORFs of SmVASL message are represented by thick colored lines, and the lengths of the deduced encoded proteins are displayed at the right side of each splice variant. The asterisks next to SmVASLv6, SmVASLv6a and SmVASLv6b indicate that the latter two are the result of a 3'-RACE-PCR experiment (3'-RACE primers represented by blue arrows); B: Local alignment (BLAST) showing the conserved region of SmVASLv6a and human vasohibin 2; C: Agarose gel electrophoresis of RT-PCR products from a reaction performed with primers indicated in panel A with green arrows. RT indicates that cDNA was synthesized by Reverse Transcriptase with poly-dT priming using RNA as template, and PCR was subsequently performed. No RT indicates a negative control where PCR was performed with an RNA sample incubated with poly-dT but no reverse transcriptase, to control for the absence of genomic DNA contamination.
Mentions: Vasohibins constitute a recently described family of endothelium-derived angiogenesis inhibitors in humans [35,36]. The presence of a Vasohibin ortholog in schistosomes might suggest a potential angiogenesis inhibition process in the host, mediated by schistosomes' molecules. Complete sequencing of clone MA3-9999U-M294-F04-U.B, the longest clone in SmAE cluster C605907.1, showed a transcript with 975 bases (Figure 4A) that we named SmVASL for S. mansoni Vasohibin-like gene. BLASTP comparison to Swiss-Prot/TrEMBL showed the best match (48% identity and 58% similarity over 90 amino acids) to vasohibin 2 ([Swissprot: Q86V25] or FLJ12505 protein), a recently described human vasohibin-like protein [36]. The amino portion of SmVASL deduced protein (starting at Leu4) did align to Leu142 of human vasohibin 2, thus suggesting that SmVASL represented a partial sequence of the S. mansoni ortholog.

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