Limits...
In silico ionomics segregates parasitic from free-living eukaryotes.

Greganova E, Steinmann M, Mäser P, Fankhauser N - Genome Biol Evol (2013)

Bottom Line: Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand.Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites.Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism.

View Article: PubMed Central - PubMed

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

ABSTRACT
Ion transporters are fundamental to life. Due to their ancient origin and conservation in sequence, ion transporters are also particularly well suited for comparative genomics of distantly related species. Here, we perform genome-wide ion transporter profiling as a basis for comparative genomics of eukaryotes. From a given predicted proteome, we identify all bona fide ion channels, ion porters, and ion pumps. Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand. This surprising finding indicates strong convergent evolution of the parasites regarding the acquisition and homeostasis of inorganic ions. Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites. Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism. This finding is in agreement with the phenomenon of iron withholding as a primordial antimicrobial strategy of infected mammals.

Show MeSH

Related in: MedlinePlus

Random forest analysis measuring the effect of each ion transporter family on the ability to distinguish obligate endoparasites. The typical substrates of the transporters are indicated on the right.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3814192&req=5

evt134-F5: Random forest analysis measuring the effect of each ion transporter family on the ability to distinguish obligate endoparasites. The typical substrates of the transporters are indicated on the right.

Mentions: We concluded that the topology of the tree in figure 4 reflects convergent evolution between obligate endoparasitic eukaryotes, in particular loss of ion channel and ion porter genes. To elucidate which of the ion transporter families contribute the strongest signal for the observed distinction of the parasites, we performed a random forest classification after having assigned to each species an attribute parasite or nonparasite, the latter also comprising facultative parasitic species. The same input vectors were used as for hierarchical clustering (fig. 4). The random forest method generated training and validation sets by random resampling of the input vectors. A total of 5,000 trees were used to determine the impact of each ion transporter family on prediction accuracy regarding parasite status. Gini coefficients served as a measure for inequality (node impurity) of the predictions. Figure 5 depicts the impact of individual transporter families on the sum of all Gini coefficients in the forest. Five families stood out with a mean Gini decrease >1, namely the high-affinity ammonia transporters (AMT; 1.A.11.2), the natural resistance-associated macrophage proteins (NRAMP; 2.A.55), the BOR1-type boron transporters (2.A.31.3), the ZIP family of zinc–iron permeases (2.A.5), and the heavy metal transporter of the ABC-B superfamily (HMT; 3.A.1.210). BOR1 transporters were missing in all obligate endoparasites. ZIP and HMT transporters were present but different, consistently returning lower scores against the respective profiles than the hits from nonparasitic eukaryotes. AMT transporters were absent except in T. cruzi, and NRAMP transporters only occurred in Plasmodium spp. and Tox. gondii (supplementary table S3, Supplementary Material online). Note that only the combined information from the various ion transporter families distinguished the parasites.Fig. 5.—


In silico ionomics segregates parasitic from free-living eukaryotes.

Greganova E, Steinmann M, Mäser P, Fankhauser N - Genome Biol Evol (2013)

Random forest analysis measuring the effect of each ion transporter family on the ability to distinguish obligate endoparasites. The typical substrates of the transporters are indicated on the right.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814192&req=5

evt134-F5: Random forest analysis measuring the effect of each ion transporter family on the ability to distinguish obligate endoparasites. The typical substrates of the transporters are indicated on the right.
Mentions: We concluded that the topology of the tree in figure 4 reflects convergent evolution between obligate endoparasitic eukaryotes, in particular loss of ion channel and ion porter genes. To elucidate which of the ion transporter families contribute the strongest signal for the observed distinction of the parasites, we performed a random forest classification after having assigned to each species an attribute parasite or nonparasite, the latter also comprising facultative parasitic species. The same input vectors were used as for hierarchical clustering (fig. 4). The random forest method generated training and validation sets by random resampling of the input vectors. A total of 5,000 trees were used to determine the impact of each ion transporter family on prediction accuracy regarding parasite status. Gini coefficients served as a measure for inequality (node impurity) of the predictions. Figure 5 depicts the impact of individual transporter families on the sum of all Gini coefficients in the forest. Five families stood out with a mean Gini decrease >1, namely the high-affinity ammonia transporters (AMT; 1.A.11.2), the natural resistance-associated macrophage proteins (NRAMP; 2.A.55), the BOR1-type boron transporters (2.A.31.3), the ZIP family of zinc–iron permeases (2.A.5), and the heavy metal transporter of the ABC-B superfamily (HMT; 3.A.1.210). BOR1 transporters were missing in all obligate endoparasites. ZIP and HMT transporters were present but different, consistently returning lower scores against the respective profiles than the hits from nonparasitic eukaryotes. AMT transporters were absent except in T. cruzi, and NRAMP transporters only occurred in Plasmodium spp. and Tox. gondii (supplementary table S3, Supplementary Material online). Note that only the combined information from the various ion transporter families distinguished the parasites.Fig. 5.—

Bottom Line: Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand.Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites.Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism.

View Article: PubMed Central - PubMed

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

ABSTRACT
Ion transporters are fundamental to life. Due to their ancient origin and conservation in sequence, ion transporters are also particularly well suited for comparative genomics of distantly related species. Here, we perform genome-wide ion transporter profiling as a basis for comparative genomics of eukaryotes. From a given predicted proteome, we identify all bona fide ion channels, ion porters, and ion pumps. Concentrating on unicellular eukaryotes (n = 37), we demonstrate that clustering of species according to their repertoire of ion transporters segregates obligate endoparasites (n = 23) on the one hand, from free-living species and facultative parasites (n = 14) on the other hand. This surprising finding indicates strong convergent evolution of the parasites regarding the acquisition and homeostasis of inorganic ions. Random forest classification identifies transporters of ammonia, plus transporters of iron and other transition metals, as the most informative for distinguishing the obligate parasites. Thus, in silico ionomics further underscores the importance of iron in infection biology and suggests access to host sources of nitrogen and transition metals to be selective forces in the evolution of parasitism. This finding is in agreement with the phenomenon of iron withholding as a primordial antimicrobial strategy of infected mammals.

Show MeSH
Related in: MedlinePlus