MBE Advance Access originally published online on April 28, 2006
Molecular Biology and Evolution 2006 23(7):1341-1344; doi:10.1093/molbev/msl001
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Letter |
Evolution of the Isd11–IscS Complex Reveals a Single 
-Proteobacterial Endosymbiosis for All Eukaryotes
* School of Biosciences, University of Exeter, Exeter, United Kingdom; and School of Biological and Chemical Sciences, Queen Mary, University of London, London, United Kingdom
E-mail: m.vandergiezen{at}qmul.ac.uk.
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Abstract |
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Giardia and Trichomonas are eukaryotes without standard mitochondria but contain mitochondrial-type
-proteobacterium–derived iron–sulfur cluster (ISC) assembly proteins, located to mitosomes in Giardia and hydrogenosomes in Trichomonas. Although these data suggest a single common endosymbiotic ancestry for mitochondria, mitosomes, and hydrogenosomes, separate origins are still being proposed. Here, we present a bioinformatic analysis of Isd11, a recently described essential component of the mitochondrial ISC assembly pathway. Isd11 is unique to eukaryotes but functions closely with the -proteobacterium–derived cysteine desulfurase IscS. We demonstrate the presence of homologues of Isd11 in all 5 eukaryotic supergroups sampled, including hydrogenosomal and mitosomal lineages. The eukaryotic invention of Isd11 as a functional partner to IscS directly implies a single shared -proteobacterial endosymbiotic ancestry for all eukaryotes. This pinpoints the -proteobacterial endosymbiosis to before the last common ancestor of all eukaryotes without ambiguity.
Key Words: mitochondria • mitosome • hydrogenosome • iron–sulfur cluster • origin of the eukaryotic cell
Endosymbiosis played a key role in the evolution of eukaryotic cells, but the number and ancestry of endosymbiotic events remains contentious (Martin and Müller 1998
; Martin et al. 2001; Dyall et al. 2004). Did organelles such as hydrogenosomes, mitosomes, and mitochondria originate separately from different symbiotic bacteria or from just one endosymbiosis (Dyall et al. 2004; Embley and Martin 2006)?
In many species, mitochondria are essential for energy transduction by oxidative phosphorylation. However, systematic knock-out of mitochondrial proteins has demonstrated that yeast mitochondria perform only one essential function, the assembly of iron–sulfur clusters (ISCs) (Lill and Mühlenhoff 2005). This suggests that mitochondria are retained for compartmentalized ISC assembly (Lill and Mühlenhoff 2005; van der Giezen and Tovar 2005).
Wiedemann et al. (2006) and Adam et al. (2006) recently demonstrated that the ISC protein Isd11 is localized within mitochondria and is essential for ISC biogenesis in yeast and that Isd11 forms a complex with Nfs1. Nfs1 and its orthologue IscS play a role as a vital cysteine desulfurase of the ISC assembly machinery (Adam et al. 2006; Wiedemann et al. 2006). Isd11 is suggested to function as an adapter and stabilizer of Nfs1 (Adam et al. 2006; Wiedemann et al. 2006). Homologues of the Isd11 gene have been detected in plant, fungi, and animal genomes, which possess mitochondria, but no prokaryote homologue has been found (Wiedemann et al. 2006). This suggests that Isd11 is a eukaryotic molecular innovation that arose, at the earliest, during the primary process of endosymbiosis that gave rise to mitochondria and which installed IscS, the functional partner of Isd11 (Adam et al. 2006; Wiedemann et al. 2006), in the eukaryotes. To test this hypothesis, we searched for putative homologues from available prokaryotic genomes using multiple PSI-Blast searches of GenBank and confirmed, given current sampling, that the Isd11 gene is exclusive to eukaryotes. Blast searches of all available eukaryotic genomes revealed the presence of putative IscS homologues in all eukaryotes surveyed, except for incomplete genome projects (fig. 1A). Further, comparative genome analyses detected putative homologues of Isd11 in numerous eukaryotes including hydrogenosomal and mitosomal lineages. BlastP analyses demonstrated 47% amino acid sequence identity with the yeast Isd11 protein for both the Trichomonas vaginalis and Nosema locustae (synonym Antonospora locustae) putative Isd11 proteins. Together with the protein alignment, this suggests that the amitochondrial sequences are true homologues (fig. 1B). Isd11 has a high helical propensity (see fig. 1B). Interestingly, neither PSSM (Kelley et al. 2000) nor the newer PHYRE algorithm (http://www.sbg.bio.ic.ac.uk/phyre/) recognize any known fold in Isd11, suggesting that Isd11 might represent a new type of protein fold. Further structural studies, especially in complex with Nfs1, should prove interesting. All the putative Isd11 homologues analyzed are predicted to contain 3 -helices, consistent with their shared homology. Bioinformatic predictions of mitochondrial targeting for Isd11 were unconvincing for all lineages investigated, including the yeast Isd11, known to be located in mitochondria (Adam et al. 2006; Wiedemann et al. 2006) but demonstrated a candidate target peptide in the putative Isd11 of T. vaginalis (fig. 1B and Supplementary Table 1, Supplementary Material online).
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The process of horizontal gene transfers (HGTs) could theoretically distribute genes of endosymbiotic ancestry into lineages that did not undergo the original endosymbiosis (Roger et al. 1998
). The Isd11 gene is short (encoding 
90 amino acids) and unlikely to be a reliable gene for phylogeny; indeed, like many single-gene eukaryote phylogenies, the terminal branches were unresolved (fig. 2A—see branches within the gray zone). Comparison tests of alternative terminal branching orders confirmed that many of the pictured terminal node relationships are unresolved (see Supplementary Methods and Supplementary Figure 1, Supplementary Material online). However, phylogenetic analysis did not provide strong support for HGT over the more parsimonious scenario of vertical inheritance for the T. vaginalis Isd11 gene (fig. 2A). Furthermore, Nosema Isd11 consistently grouped within a weakly resolved clade of alveolates and formed a moderately supported sister group relationship with the Plasmodium parasites in all analyses. Plasmodium and Microsporidia are intracellular parasites that infect insects, and in both Plasmodium and Microsporidia, there are reported cases of HGT between these parasites and cells that they come into close contact with (Richards et al. 2003). Comparative topology tests could not reject an alternative topology where the Microsporidia branched below the alveolate group (e.g., "approximately unbiased" test, P = 0.49; Shimodaira and Hasegawa 2001), which is inconsistent with a Plasmodium-to-Microsporidia gene transfer. However, taken together, we cannot exclude a case of HGT between the Apicomplexa (Plasmodium) and Microsporidia (Nosema) based on the Isd11 phylogeny, but this scenario is less parsimonious than vertical inheritance.
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In conclusion, we suggest that Isd11 originated during or shortly after the single endosymbiosis that gave rise to mitochondria, hydrogenosomes, and mitosomes. Isd11 evolved as an exclusively eukaryotic addition to the
-proteobacterium–derived ISC biogenesis pathway. Like the ISC biogenesis pathway itself (Tachezy et al. 2001), Isd11 has been conserved in hydrogenosomal and mitosomal lineages. We demonstrate that Isd11 represents a unique shared derived character of all sampled eukaryote supergroups (fig. 2B), including mitochondrial, hydrogenosomal, and mitosomal lineages. Isd11 therefore pinpoints the ancestry of the eukaryotic ISC biogenesis pathway to a single endosymbiotic event. The alternative assumption of separate origins of the IscS–Isd11 complex requires Isd11 to have evolved convergently in separate lineages and IscS to be acquired separately from 2 closely related proteobacteria, whereas separate endosymbiotic origins for any combination of the 3 organelles must include a process of endosymbiotic replacement (Dyall et al. 2004); these alternative scenarios may be possible but are very unparsimonious. Similarities in mitochondrial, hydrogenosomal, and mitosomal N-terminal targeting peptides also hint at a shared derived import machinery in all 3 organelle types, suggesting a common origin of these organelles (van der Giezen and Tovar 2005). However, although genes encoding components of a mitochondrial import machinery have been identified in mitosomal lineages (Henriquez et al. 2005), only one putative component of the mitochondrial import machinery has been identified in hydrogenosomes (Dolezal et al. 2005). In conclusion, the IscS–Isd11 complex was present in the last common ancestor of all the eukaryotes prior to the division of all eukaryotic supergroups (Simpson and Roger 2004). Therefore, the -proteobacterial endosymbiosis is placed firmly before the radiation of all eukaryotes (fig. 2B). |
Supplementary Material |
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TOPAbstractSupplementary MaterialAcknowledgementsReferences |
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Additional detailed methods (Supplementary Methods), results of alternative topology comparison tests (Supplementary Figure 1), and comparisons of putative Isd11 mitochondria targeting peptides (Supplementary Table 1) are available at Molecular Biology and Evolution online (http://www.mbe.oxfordjournals.org/).
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Acknowledgements |
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TOPAbstractSupplementary MaterialAcknowledgementsReferences |
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We are grateful to The Institute for Genomic Research (http://www.tigr.org), The Department of Energy (http://www.jgi.doe.gov/), Genoscope (http://www.genoscope.cns.fr/), and M. B. L. Woods Hole (http://jbpc.mbl.edu/Nosema/) for making their genome data available (01/06). T.A.R. thanks the Department for Environment, Food and Rural Affairs for fellowship support. We thank N. J. Talbot and J. F. Allen for comments and P. Foster with assistance with topology comparison tests.
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Footnotes |
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William Martin, Associate Editor
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