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The genome of the heartworm, Dirofilaria immitis, reveals drug and vaccine targets.

Godel C, Kumar S, Koutsovoulos G, Ludin P, Nilsson D, Comandatore F, Wrobel N, Thompson M, Schmid CD, Goto S, Bringaud F, Wolstenholme A, Bandi C, Epe C, Kaminsky R, Blaxter M, Mäser P - FASEB J. (2012)

Bottom Line: The D. immitis genome harbors neither DNA transposons nor active retrotransposons, and there is very little genetic variation between two sequenced isolates from Europe and the United States.Comparing the proteome of D. immitis with other nematodes and with mammalian hosts, we identify families of potential drug targets, immune modulators, and vaccine candidates.This genome sequence will support the development of new tools against dirofilariasis and aid efforts to combat related human pathogens, the causative agents of lymphatic filariasis and river blindness.

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.

ABSTRACT
The heartworm Dirofilaria immitis is an important parasite of dogs. Transmitted by mosquitoes in warmer climatic zones, it is spreading across southern Europe and the Americas at an alarming pace. There is no vaccine, and chemotherapy is prone to complications. To learn more about this parasite, we have sequenced the genomes of D. immitis and its endosymbiont Wolbachia. We predict 10,179 protein coding genes in the 84.2 Mb of the nuclear genome, and 823 genes in the 0.9-Mb Wolbachia genome. The D. immitis genome harbors neither DNA transposons nor active retrotransposons, and there is very little genetic variation between two sequenced isolates from Europe and the United States. The differential presence of anabolic pathways such as heme and nucleotide biosynthesis hints at the intricate metabolic interrelationship between the heartworm and Wolbachia. Comparing the proteome of D. immitis with other nematodes and with mammalian hosts, we identify families of potential drug targets, immune modulators, and vaccine candidates. This genome sequence will support the development of new tools against dirofilariasis and aid efforts to combat related human pathogens, the causative agents of lymphatic filariasis and river blindness.

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Related in: MedlinePlus

Conserved and novel genes in D. immitis. The D. immitis proteome was clustered with those of B. malayi, A. suum, C. elegans, and T. spiralis. Clusters were then classified based on the membership from the five species according to the current phylogeny of the phylum Nematoda. A) Pie chart showing the distribution of classification of D. immitis proteins: D. immitis only, singletons and clusters only found in D. immitis; Onchocercidae, clusters with members only from D. immitis and B. malayi; Spiruria, clusters with members only from Onchocercidae and A. suum; Rhabditia clusters with members only from Spiruria and C. elegans; Nematoda, clusters with members from all five species (i.e., Rhabditia and T. spiralis); and other patterns, clusters with members not fitting simply into the phylogenetic schema (probably arising from gene loss, lack of predictions, or failure to cluster in one or more species). B) Cluster numbers and patterns of conservation mapped onto the phylogeny of the five species.
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Figure 1: Conserved and novel genes in D. immitis. The D. immitis proteome was clustered with those of B. malayi, A. suum, C. elegans, and T. spiralis. Clusters were then classified based on the membership from the five species according to the current phylogeny of the phylum Nematoda. A) Pie chart showing the distribution of classification of D. immitis proteins: D. immitis only, singletons and clusters only found in D. immitis; Onchocercidae, clusters with members only from D. immitis and B. malayi; Spiruria, clusters with members only from Onchocercidae and A. suum; Rhabditia clusters with members only from Spiruria and C. elegans; Nematoda, clusters with members from all five species (i.e., Rhabditia and T. spiralis); and other patterns, clusters with members not fitting simply into the phylogenetic schema (probably arising from gene loss, lack of predictions, or failure to cluster in one or more species). B) Cluster numbers and patterns of conservation mapped onto the phylogeny of the five species.

Mentions: D. immitis proteins were clustered with the complete proteomes of four other nematode species. These clusters were classified and mapped onto the phylogenetic tree of the five species based on the placement of the deepest node that linked the species that contributed members (Fig. 1). The D. immitis proteome included 3199 proteins (31% of the total proteome) that were unique to this species, a proportion similar to that found in B. malayi (27%), but many fewer (and a lower proportion) compared with those for the other species (for example, C. elegans had 63% of its proteome in species-unique clusters). This difference may be partly due to the 850 proteins in clusters uniquely shared by the relatively closely related D. immitis and B. malayi, but these clusters only raise the proportion of proteins in phylogenetically local clusters to 47%.


The genome of the heartworm, Dirofilaria immitis, reveals drug and vaccine targets.

Godel C, Kumar S, Koutsovoulos G, Ludin P, Nilsson D, Comandatore F, Wrobel N, Thompson M, Schmid CD, Goto S, Bringaud F, Wolstenholme A, Bandi C, Epe C, Kaminsky R, Blaxter M, Mäser P - FASEB J. (2012)

Conserved and novel genes in D. immitis. The D. immitis proteome was clustered with those of B. malayi, A. suum, C. elegans, and T. spiralis. Clusters were then classified based on the membership from the five species according to the current phylogeny of the phylum Nematoda. A) Pie chart showing the distribution of classification of D. immitis proteins: D. immitis only, singletons and clusters only found in D. immitis; Onchocercidae, clusters with members only from D. immitis and B. malayi; Spiruria, clusters with members only from Onchocercidae and A. suum; Rhabditia clusters with members only from Spiruria and C. elegans; Nematoda, clusters with members from all five species (i.e., Rhabditia and T. spiralis); and other patterns, clusters with members not fitting simply into the phylogenetic schema (probably arising from gene loss, lack of predictions, or failure to cluster in one or more species). B) Cluster numbers and patterns of conservation mapped onto the phylogeny of the five species.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3475251&req=5

Figure 1: Conserved and novel genes in D. immitis. The D. immitis proteome was clustered with those of B. malayi, A. suum, C. elegans, and T. spiralis. Clusters were then classified based on the membership from the five species according to the current phylogeny of the phylum Nematoda. A) Pie chart showing the distribution of classification of D. immitis proteins: D. immitis only, singletons and clusters only found in D. immitis; Onchocercidae, clusters with members only from D. immitis and B. malayi; Spiruria, clusters with members only from Onchocercidae and A. suum; Rhabditia clusters with members only from Spiruria and C. elegans; Nematoda, clusters with members from all five species (i.e., Rhabditia and T. spiralis); and other patterns, clusters with members not fitting simply into the phylogenetic schema (probably arising from gene loss, lack of predictions, or failure to cluster in one or more species). B) Cluster numbers and patterns of conservation mapped onto the phylogeny of the five species.
Mentions: D. immitis proteins were clustered with the complete proteomes of four other nematode species. These clusters were classified and mapped onto the phylogenetic tree of the five species based on the placement of the deepest node that linked the species that contributed members (Fig. 1). The D. immitis proteome included 3199 proteins (31% of the total proteome) that were unique to this species, a proportion similar to that found in B. malayi (27%), but many fewer (and a lower proportion) compared with those for the other species (for example, C. elegans had 63% of its proteome in species-unique clusters). This difference may be partly due to the 850 proteins in clusters uniquely shared by the relatively closely related D. immitis and B. malayi, but these clusters only raise the proportion of proteins in phylogenetically local clusters to 47%.

Bottom Line: The D. immitis genome harbors neither DNA transposons nor active retrotransposons, and there is very little genetic variation between two sequenced isolates from Europe and the United States.Comparing the proteome of D. immitis with other nematodes and with mammalian hosts, we identify families of potential drug targets, immune modulators, and vaccine candidates.This genome sequence will support the development of new tools against dirofilariasis and aid efforts to combat related human pathogens, the causative agents of lymphatic filariasis and river blindness.

View Article: PubMed Central - PubMed

Affiliation: Swiss Tropical and Public Health Institute, Basel, Switzerland.

ABSTRACT
The heartworm Dirofilaria immitis is an important parasite of dogs. Transmitted by mosquitoes in warmer climatic zones, it is spreading across southern Europe and the Americas at an alarming pace. There is no vaccine, and chemotherapy is prone to complications. To learn more about this parasite, we have sequenced the genomes of D. immitis and its endosymbiont Wolbachia. We predict 10,179 protein coding genes in the 84.2 Mb of the nuclear genome, and 823 genes in the 0.9-Mb Wolbachia genome. The D. immitis genome harbors neither DNA transposons nor active retrotransposons, and there is very little genetic variation between two sequenced isolates from Europe and the United States. The differential presence of anabolic pathways such as heme and nucleotide biosynthesis hints at the intricate metabolic interrelationship between the heartworm and Wolbachia. Comparing the proteome of D. immitis with other nematodes and with mammalian hosts, we identify families of potential drug targets, immune modulators, and vaccine candidates. This genome sequence will support the development of new tools against dirofilariasis and aid efforts to combat related human pathogens, the causative agents of lymphatic filariasis and river blindness.

Show MeSH
Related in: MedlinePlus