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

Ion transporter repertoires of unicellular eukaryotes. The heatmap represents the best HMMer scores achieved by the different proteomes (rows) against the profiles for the different families of ion transporters (columns). Profiles that did not return a hit of score >20 in any of the proteomes are not shown. The data are in supplementary table S3, Supplementary Material online.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

evt134-F3: Ion transporter repertoires of unicellular eukaryotes. The heatmap represents the best HMMer scores achieved by the different proteomes (rows) against the profiles for the different families of ion transporters (columns). Profiles that did not return a hit of score >20 in any of the proteomes are not shown. The data are in supplementary table S3, Supplementary Material online.

Mentions: The numbers of predicted transporters per proteome being a somewhat crude and arbitrary measure, we used the achieved scores against the ion transporter profiles as a refined and unbiased parameter of a given proteome. Thus, an “ionomic landscape” vector was built for every proteome, consisting of the top scores against the ion transporter profiles of supplementary table S1, Supplementary Material online. Figure 3 depicts these vectors as a heat map where darker shades represent higher scores. The data are shown in supplementary table S3, Supplementary Material online (only 65 different ion transporter profiles were used as 10 appeared to be prokaryote-specific and did not return a hit in any of the analyzed eukaryotes). Although the different unicellular eukaryotes analyzed achieved similar top scores toward the known families of ion pumps (fig. 3, right), the situation was different regarding ion channels and ion porters, which appeared to be generally underrepresented in obligate endoparasites as compared with free-living species or facultative parasites (fig. 3, left and middle). Parasites such as Cryptosporidia, Microsporidia, or Theileria appeared to be devoid of bona fide cation channels. The ionomic landscape vectors were hierarchically clustered in an unbiased way: A selection of distance metrics and clustering algorithms were combined with the program pvclust, and the resulting trees were ranked based on the number of leaves in statistically significant clusters. The best scoring tree is shown in figure 4. Its topology deviates from a phylogenetic tree in several aspects. The microsporidian E. cuniculi does not cluster with the fungi. The free-living amoebozoa D. discoideum and P. pallidum do, whereas Ent. histolytica groups with Tri. vaginalis. The ciliate Par. tetraurelia clusters with the free-living green algae rather than with alveolates (which are all parasitic), and the trypanosomatids are sister to Toxoplasma and the malaria parasites. Strikingly, the first and main division of the ionomic tree of unicellular eukaryotes is into eukaryotes with free-living life stages on one side and obligate endoparasites on the other. This separation was statistically significant as the probability of splitting the 37 analyzed species by chance into the 23 obligate parasites and 14 facultative parasites or free-living species equals (23! × 14! × 2)/37! = 3.3 × 10−10. In addition, we carried out the same procedure of representing and clustering HMMer hits based on sets of 65 randomly chosen profiles from the Pfam database of protein families (Punta et al. 2011); a separation of parasites from free-living species never occurred (data not shown).Fig. 3.—


In silico ionomics segregates parasitic from free-living eukaryotes.

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

Ion transporter repertoires of unicellular eukaryotes. The heatmap represents the best HMMer scores achieved by the different proteomes (rows) against the profiles for the different families of ion transporters (columns). Profiles that did not return a hit of score >20 in any of the proteomes are not shown. The data are in supplementary table S3, Supplementary Material online.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

evt134-F3: Ion transporter repertoires of unicellular eukaryotes. The heatmap represents the best HMMer scores achieved by the different proteomes (rows) against the profiles for the different families of ion transporters (columns). Profiles that did not return a hit of score >20 in any of the proteomes are not shown. The data are in supplementary table S3, Supplementary Material online.
Mentions: The numbers of predicted transporters per proteome being a somewhat crude and arbitrary measure, we used the achieved scores against the ion transporter profiles as a refined and unbiased parameter of a given proteome. Thus, an “ionomic landscape” vector was built for every proteome, consisting of the top scores against the ion transporter profiles of supplementary table S1, Supplementary Material online. Figure 3 depicts these vectors as a heat map where darker shades represent higher scores. The data are shown in supplementary table S3, Supplementary Material online (only 65 different ion transporter profiles were used as 10 appeared to be prokaryote-specific and did not return a hit in any of the analyzed eukaryotes). Although the different unicellular eukaryotes analyzed achieved similar top scores toward the known families of ion pumps (fig. 3, right), the situation was different regarding ion channels and ion porters, which appeared to be generally underrepresented in obligate endoparasites as compared with free-living species or facultative parasites (fig. 3, left and middle). Parasites such as Cryptosporidia, Microsporidia, or Theileria appeared to be devoid of bona fide cation channels. The ionomic landscape vectors were hierarchically clustered in an unbiased way: A selection of distance metrics and clustering algorithms were combined with the program pvclust, and the resulting trees were ranked based on the number of leaves in statistically significant clusters. The best scoring tree is shown in figure 4. Its topology deviates from a phylogenetic tree in several aspects. The microsporidian E. cuniculi does not cluster with the fungi. The free-living amoebozoa D. discoideum and P. pallidum do, whereas Ent. histolytica groups with Tri. vaginalis. The ciliate Par. tetraurelia clusters with the free-living green algae rather than with alveolates (which are all parasitic), and the trypanosomatids are sister to Toxoplasma and the malaria parasites. Strikingly, the first and main division of the ionomic tree of unicellular eukaryotes is into eukaryotes with free-living life stages on one side and obligate endoparasites on the other. This separation was statistically significant as the probability of splitting the 37 analyzed species by chance into the 23 obligate parasites and 14 facultative parasites or free-living species equals (23! × 14! × 2)/37! = 3.3 × 10−10. In addition, we carried out the same procedure of representing and clustering HMMer hits based on sets of 65 randomly chosen profiles from the Pfam database of protein families (Punta et al. 2011); a separation of parasites from free-living species never occurred (data not shown).Fig. 3.—

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