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Molecular determinants archetypical to the phylum Nematoda.

Yin Y, Martin J, Abubucker S, Wang Z, Wyrwicz L, Rychlewski L, McCarter JP, Wilson RK, Mitreva M - BMC Genomics (2009)

Bottom Line: Nearly 1,600 of the multi-species families did not share homology to Pfam domains, including a total of 758 restricted to Nematoda.Features of these protein families were revealed through extrapolation of essential functions from observed RNAi phenotypes in C. elegans, bioinformatics-based functional annotations, identification of distant homology based on protein folds, and prediction of expression at accessible nematode surfaces.This study identified and characterized the molecular determinants that help in defining the phylum Nematoda, and therefore improved our understanding of nematode protein evolution and provided novel insights for the development of next generation parasite control strategies.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Genome Center, Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA. yyin@watson.wustl.edu

ABSTRACT

Background: Nematoda diverged from other animals between 600-1,200 million years ago and has become one of the most diverse animal phyla on earth. Most nematodes are free-living animals, but many are parasites of plants and animals including humans, posing major ecological and economical challenges around the world.

Results: We investigated phylum-specific molecular characteristics in Nematoda by exploring over 214,000 polypeptides from 32 nematode species including 27 parasites. Over 50,000 nematode protein families were identified based on primary sequence, including approximately 10% with members from at least three different species. Nearly 1,600 of the multi-species families did not share homology to Pfam domains, including a total of 758 restricted to Nematoda. Majority of the 462 families that were conserved among both free-living and parasitic species contained members from multiple nematode clades, yet approximately 90% of the 296 parasite-specific families originated only from a single clade. Features of these protein families were revealed through extrapolation of essential functions from observed RNAi phenotypes in C. elegans, bioinformatics-based functional annotations, identification of distant homology based on protein folds, and prediction of expression at accessible nematode surfaces. In addition, we identified a group of nematode-restricted sequence features in energy-generating electron transfer complexes as potential targets for new chemicals with minimal or no toxicity to the host.

Conclusion: This study identified and characterized the molecular determinants that help in defining the phylum Nematoda, and therefore improved our understanding of nematode protein evolution and provided novel insights for the development of next generation parasite control strategies.

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Related in: MedlinePlus

Nematode-specific sequence features in the NF families. Insertions specific to nematodes were evident in the global multiple alignment among members of NF_0313_0956 and orthologous proteins from non-nematode species. NF_0313_0956 included SS00822 (Strongyloides stercoralis), 14968.m01483 (Brugia malayi), F45H10.3 (Caenorhabditis elegans), gi-39591288-emb-CAE73341.1-(Caenorhabditis briggsae), cr01.Contig9.wum.334.1 (Caenorhabditis remanei), AE04133 (Ancylostoma ceylanicum), HC05738 (Haemonchus contortus), NB03814 (Nippostrongylus brasiliensis), OS04039 (Ostertagia ostertagi), PT04092 (Parastrongyloides trichosuri), and MH00982 (Meloidogyne hapla). Non-nematode orthologous proteins were those annotated as the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 7 (KO: K03951) from fly, bovine, mouse, rat, and human.
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Figure 4: Nematode-specific sequence features in the NF families. Insertions specific to nematodes were evident in the global multiple alignment among members of NF_0313_0956 and orthologous proteins from non-nematode species. NF_0313_0956 included SS00822 (Strongyloides stercoralis), 14968.m01483 (Brugia malayi), F45H10.3 (Caenorhabditis elegans), gi-39591288-emb-CAE73341.1-(Caenorhabditis briggsae), cr01.Contig9.wum.334.1 (Caenorhabditis remanei), AE04133 (Ancylostoma ceylanicum), HC05738 (Haemonchus contortus), NB03814 (Nippostrongylus brasiliensis), OS04039 (Ostertagia ostertagi), PT04092 (Parastrongyloides trichosuri), and MH00982 (Meloidogyne hapla). Non-nematode orthologous proteins were those annotated as the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 7 (KO: K03951) from fly, bovine, mouse, rat, and human.

Mentions: More interestingly, we were able to identify unique sequence features of these nematode proteins, such as nematode-specific insertions and deletions, in all the eight NFn families with KEGG annotations. Such nematode-specific features may have prevented their homology from being identified in our initial screening. For example, members of NFn family NF_0313_0956 were mapped to KO: K03951 as the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 7. Indeed, these nematode sequences could be forcibly aligned with the group of proteins from non-nematode organisms that were assigned to the same KEGG entry, after allowing two fragments of nematode-specific insertions (Figure 4). The lack of a homologous 3D model of this enzyme made it impossible to investigate the impact on its structure caused by these insertions, but they likely created additional loops in the nematode proteins that may introduce novel functional features specific to Nematoda. These results demonstrated the mechanism of directed diversification of existing protein folds in these proteins during nematode evolution.


Molecular determinants archetypical to the phylum Nematoda.

Yin Y, Martin J, Abubucker S, Wang Z, Wyrwicz L, Rychlewski L, McCarter JP, Wilson RK, Mitreva M - BMC Genomics (2009)

Nematode-specific sequence features in the NF families. Insertions specific to nematodes were evident in the global multiple alignment among members of NF_0313_0956 and orthologous proteins from non-nematode species. NF_0313_0956 included SS00822 (Strongyloides stercoralis), 14968.m01483 (Brugia malayi), F45H10.3 (Caenorhabditis elegans), gi-39591288-emb-CAE73341.1-(Caenorhabditis briggsae), cr01.Contig9.wum.334.1 (Caenorhabditis remanei), AE04133 (Ancylostoma ceylanicum), HC05738 (Haemonchus contortus), NB03814 (Nippostrongylus brasiliensis), OS04039 (Ostertagia ostertagi), PT04092 (Parastrongyloides trichosuri), and MH00982 (Meloidogyne hapla). Non-nematode orthologous proteins were those annotated as the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 7 (KO: K03951) from fly, bovine, mouse, rat, and human.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2666764&req=5

Figure 4: Nematode-specific sequence features in the NF families. Insertions specific to nematodes were evident in the global multiple alignment among members of NF_0313_0956 and orthologous proteins from non-nematode species. NF_0313_0956 included SS00822 (Strongyloides stercoralis), 14968.m01483 (Brugia malayi), F45H10.3 (Caenorhabditis elegans), gi-39591288-emb-CAE73341.1-(Caenorhabditis briggsae), cr01.Contig9.wum.334.1 (Caenorhabditis remanei), AE04133 (Ancylostoma ceylanicum), HC05738 (Haemonchus contortus), NB03814 (Nippostrongylus brasiliensis), OS04039 (Ostertagia ostertagi), PT04092 (Parastrongyloides trichosuri), and MH00982 (Meloidogyne hapla). Non-nematode orthologous proteins were those annotated as the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 7 (KO: K03951) from fly, bovine, mouse, rat, and human.
Mentions: More interestingly, we were able to identify unique sequence features of these nematode proteins, such as nematode-specific insertions and deletions, in all the eight NFn families with KEGG annotations. Such nematode-specific features may have prevented their homology from being identified in our initial screening. For example, members of NFn family NF_0313_0956 were mapped to KO: K03951 as the NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 7. Indeed, these nematode sequences could be forcibly aligned with the group of proteins from non-nematode organisms that were assigned to the same KEGG entry, after allowing two fragments of nematode-specific insertions (Figure 4). The lack of a homologous 3D model of this enzyme made it impossible to investigate the impact on its structure caused by these insertions, but they likely created additional loops in the nematode proteins that may introduce novel functional features specific to Nematoda. These results demonstrated the mechanism of directed diversification of existing protein folds in these proteins during nematode evolution.

Bottom Line: Nearly 1,600 of the multi-species families did not share homology to Pfam domains, including a total of 758 restricted to Nematoda.Features of these protein families were revealed through extrapolation of essential functions from observed RNAi phenotypes in C. elegans, bioinformatics-based functional annotations, identification of distant homology based on protein folds, and prediction of expression at accessible nematode surfaces.This study identified and characterized the molecular determinants that help in defining the phylum Nematoda, and therefore improved our understanding of nematode protein evolution and provided novel insights for the development of next generation parasite control strategies.

View Article: PubMed Central - HTML - PubMed

Affiliation: The Genome Center, Department of Genetics, Washington University School of Medicine, St Louis, Missouri, USA. yyin@watson.wustl.edu

ABSTRACT

Background: Nematoda diverged from other animals between 600-1,200 million years ago and has become one of the most diverse animal phyla on earth. Most nematodes are free-living animals, but many are parasites of plants and animals including humans, posing major ecological and economical challenges around the world.

Results: We investigated phylum-specific molecular characteristics in Nematoda by exploring over 214,000 polypeptides from 32 nematode species including 27 parasites. Over 50,000 nematode protein families were identified based on primary sequence, including approximately 10% with members from at least three different species. Nearly 1,600 of the multi-species families did not share homology to Pfam domains, including a total of 758 restricted to Nematoda. Majority of the 462 families that were conserved among both free-living and parasitic species contained members from multiple nematode clades, yet approximately 90% of the 296 parasite-specific families originated only from a single clade. Features of these protein families were revealed through extrapolation of essential functions from observed RNAi phenotypes in C. elegans, bioinformatics-based functional annotations, identification of distant homology based on protein folds, and prediction of expression at accessible nematode surfaces. In addition, we identified a group of nematode-restricted sequence features in energy-generating electron transfer complexes as potential targets for new chemicals with minimal or no toxicity to the host.

Conclusion: This study identified and characterized the molecular determinants that help in defining the phylum Nematoda, and therefore improved our understanding of nematode protein evolution and provided novel insights for the development of next generation parasite control strategies.

Show MeSH
Related in: MedlinePlus