DOI: 10.1038/s41467-018-03923-4. Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasites

Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasites

10.1038/s41467-018-03923-4

Crossref journal-article

Springer Science and Business Media LLC

Nature Communications (297)

Abstract

AbstractThe acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD+, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia.

Bibliography

Dean, P., Sendra, K. M., Williams, T. A., Watson, A. K., Major, P., Nakjang, S., Kozhevnikova, E., Goldberg, A. V., Kunji, E. R. S., Hirt, R. P., & Embley, T. M. (2018). Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasites. Nature Communications, 9(1).

Authors 11

P. Dean (first)
K. M. Sendra (additional)
T. A. Williams (additional)
A. K. Watson (additional)
P. Major (additional)
S. Nakjang (additional)
E. Kozhevnikova (additional)
A. V. Goldberg (additional)
E. R. S. Kunji (additional)
R. P. Hirt (additional)
T. M. Embley (additional)

References 46 Referenced 83

Didier, E. S. & Weiss, L. M. Microsporidiosis: not just in AIDS patients. Curr. Opin. Infect. Dis. 24, 490–495 (2011). (10.1097/QCO.0b013e32834aa152) / Curr. Opin. Infect. Dis. by ES Didier (2011)
Stentiford, G. D. et al. Microsporidia - emergent pathogens in the global food chain. Trends Parasitol. 32, 336–348 (2016). (10.1016/j.pt.2015.12.004) / Trends Parasitol. by GD Stentiford (2016)
Vavra, J. & Lukes, J. Microsporidia and ‘the art of living together’. Adv. Parasitol. 82, 253–319 (2013). (10.1016/B978-0-12-407706-5.00004-6) / Adv. Parasitol. by J Vavra (2013)
Katinka, M. D. et al. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414, 450–453 (2001). (10.1038/35106579) / Nature by MD Katinka (2001)
Keeling, P. J. et al. The reduced genome of the parasitic microsporidian Enterocytozoon bieneusi lacks genes for core carbon metabolism. Genome Biol. Evol. 2, 304–309 (2010). (10.1093/gbe/evq022) / Genome Biol. Evol. by PJ Keeling (2010)
Heinz, E. et al. The genome of the obligate intracellular parasite Trachipleistophora hominis: new insights into microsporidian genome dynamics and reductive evolution. PLoS Pathog. 8, e1002979 (2012). (10.1371/journal.ppat.1002979) / PLoS Pathog. by E Heinz (2012)
Williams, B. A., Hirt, R. P., Lucocq, J. M. & Embley, T. M. A mitochondrial remnant in the microsporidian Trachipleistophora hominis. Nature 418, 865–869 (2002). (10.1038/nature00949) / Nature by BA Williams (2002)
Goldberg, A. V. et al. Localization and functionality of microsporidian iron-sulphur cluster assembly proteins. Nature 452, 624–628 (2008). (10.1038/nature06606) / Nature by AV Goldberg (2008)
Freibert, S. A. et al. Evolutionary conservation and in vitro reconstitution of microsporidian iron-sulfur cluster biosynthesis. Nat. Commun. 8, 13932 (2017). (10.1038/ncomms13932) / Nat. Commun. by SA Freibert (2017)
Dolgikh, V. V., Senderskiy, I. V., Pavlova, O. A., Naumov, A. M. & Beznoussenko, G. V. Immunolocalization of an alternative respiratory chain in Antonospora (Paranosema) locustae spores: mitosomes retain their role in microsporidial energy metabolism. Eukaryot. Cell. 10, 588–593 (2011). (10.1128/EC.00283-10) / Eukaryot. Cell. by VV Dolgikh (2011)
Wiredu Boakye, D. et al. Decay of the glycolytic pathway and adaptation to intranuclear parasitism within Enterocytozoonidae microsporidia. Environ. Microbiol. 19, 2077–2089 (2017). (10.1111/1462-2920.13734) / Environ. Microbiol. by D Wiredu Boakye (2017)
Phillips, R. & Milo, R. A feeling for the numbers in biology. Proc. Natl Acad. Sci. USA 106, 21465–21471 (2009). (10.1073/pnas.0907732106) / Proc. Natl Acad. Sci. USA by R Phillips (2009)
Nakjang, S. et al. Reduction and expansion in microsporidian genome evolution: new insights from comparative genomics. Genome Biol. Evol. 5, 2285–2303 (2013). (10.1093/gbe/evt184) / Genome Biol. Evol. by S Nakjang (2013)
Tsaousis, A. D. et al. A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi. Nature 453, 553–556 (2008). (10.1038/nature06903) / Nature by AD Tsaousis (2008)
Heinz, E. et al. Plasma membrane-located purine nucleotide transport proteins are key components for host exploitation by microsporidian intracellular parasites. PLoS Pathog. 10, e1004547 (2014). (10.1371/journal.ppat.1004547) / PLoS Pathog. by E Heinz (2014)
Richards, T. A., Hirt, R. P., Williams, B. A. & Embley, T. M. Horizontal gene transfer and the evolution of parasitic protozoa. Protist 154, 17–32 (2003). (10.1078/143446103764928468) / Protist by TA Richards (2003)
James, T. Y. et al. Shared signatures of parasitism and phylogenomics unite cryptomycota and microsporidia. Curr. Biol. 23, 1548–1553 (2013). (10.1016/j.cub.2013.06.057) / Curr. Biol. by TY James (2013)
Major, P., Embley, T. M. & Williams, T. A. Phylogenetic diversity of NTT nucleotide transport proteins in free-living and parasitic bacteria and eukaryotes. Genome Biol. Evol. 9, 480–487 (2017). (10.1093/gbe/evx015) / Genome Biol. Evol. by P Major (2017)
Quandt, C. A. et al. The genome of an intranuclear parasite, Paramicrosporidium saccamoebae, reveals alternative adaptations to obligate intracellular parasitism. eLife 6, e29594 (2017). (10.7554/eLife.29594) / eLife by CA Quandt (2017)
Haag, K. L. et al. Evolution of a morphological novelty occurred before genome compaction in a lineage of extreme parasites. Proc. Natl Acad. Sci. USA 111, 15480–15485 (2014). (10.1073/pnas.1410442111) / Proc. Natl Acad. Sci. USA by KL Haag (2014)
Schonknecht, G., Weber, A. P. & Lercher, M. J. Horizontal gene acquisitions by eukaryotes as drivers of adaptive evolution. Bioessays 36, 9–20 (2014). (10.1002/bies.201300095) / Bioessays by G Schonknecht (2014)
Thornton, J. W. Resurrecting ancient genes: experimental analysis of extinct molecules. Nat. Rev. Genet. 5, 366–375 (2004). (10.1038/nrg1324) / Nat. Rev. Genet. by JW Thornton (2004)
Lartillot, N., Lepage, T. & Blanquart, S. PhyloBayes 3: a Bayesian software package for phylogenetic reconstruction and molecular dating. Bioinformatics 25, 2286–2288 (2009). (10.1093/bioinformatics/btp368) / Bioinformatics by N Lartillot (2009)
Trentmann, O., Decker, C., Winkler, H. H. & Neuhaus, H. E. Charged amino-acid residues in transmembrane domains of the plastidic ATP/ADP transporter from Arabidopsis are important for transport efficiency, substrate specificity, and counter exchange properties. Eur. J. Biochem. 267, 4098–4105 (2000). (10.1046/j.1432-1033.2000.01468.x) / Eur. J. Biochem. by O Trentmann (2000)
Tusnady, G. E. & Simon, I. The HMMTOP transmembrane topology prediction server. Bioinformatics 17, 849–850 (2001). (10.1093/bioinformatics/17.9.849) / Bioinformatics by GE Tusnady (2001)
Quistgaard, E. M., Low, C., Guettou, F. & Nordlund, P. Understanding transport by the major facilitator superfamily (MFS): structures pave the way. Nat. Rev. Mol. Cell. Biol. 17, 123–132 (2016). (10.1038/nrm.2015.25) / Nat. Rev. Mol. Cell. Biol. by EM Quistgaard (2016)
Haferkamp, I. et al. Tapping the nucleotide pool of the host: novel nucleotide carrier proteins of Protochlamydia amoebophila. Mol. Microbiol. 60, 1534–1545 (2006). (10.1111/j.1365-2958.2006.05193.x) / Mol. Microbiol. by I Haferkamp (2006)
Ohno, S. Evolution by Gene Duplication. (Springer-Verlag, Berlin, Heidelberg, 1970). (10.1007/978-3-642-86659-3)
Dean, P., Hirt, R. P. & Embley, T. M. Microsporidia: why make nucleotides if you can steal them? PLoS Pathog. 12, e1005870 (2016). (10.1371/journal.ppat.1005870) / PLoS Pathog. by P Dean (2016)
Didier, E. S. Microsporidiosis: an emerging and opportunistic infection in humans and animals. Acta Trop. 94, 61–76 (2005). (10.1016/j.actatropica.2005.01.010) / Acta Trop. by ES Didier (2005)
Traut, T. W. Physiological concentrations of purines and pyrimidines. Mol. Cell. Biochem. 140, 1–22 (1994). (10.1007/BF00928361) / Mol. Cell. Biochem. by TW Traut (1994)
Haferkamp, I. et al. A candidate NAD+transporter in an intracellular bacterial symbiont related to Chlamydiae. Nature 432, 622–625 (2004). (10.1038/nature03131) / Nature by I Haferkamp (2004)
Cuomo, C. A. et al. Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth. Genome Res. 22, 2478–2488 (2012). (10.1101/gr.142802.112) / Genome Res. by CA Cuomo (2012)
Kellis, M., Birren, B. W. & Lander, E. S. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 428, 617–624 (2004). (10.1038/nature02424) / Nature by M Kellis (2004)
Warner, J. R. The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci. 24, 437–440 (1999). (10.1016/S0968-0004(99)01460-7) / Trends Biochem. Sci. by JR Warner (1999)
Chang, Y. et al. Phylogenomic analyses Indicate that early fungi evolved digesting cell walls of algal ancestors of land plants. Genome Biol. Evol. 7, 1590–1601 (2015). (10.1093/gbe/evv090) / Genome Biol. Evol. by Y Chang (2015)
Sebe-Pedros, A., Degnan, B. M. & Ruiz-Trillo, I. The origin of Metazoa: a unicellular perspective. Nat. Rev. Genet. 18, 498–512 (2017). (10.1038/nrg.2017.21)
Field, A. S. et al. Myositis associated with a newly described microsporidian, Trachipleistophora hominis, in a patint with AIDS. J. Clin. Microbiol. 34, 2803–2811 (1996). (10.1128/jcm.34.11.2803-2811.1996) / J. Clin. Microbiol. by AS Field (1996)
Hollister, W. S., Canning, E. U. & Anderson, C. L. Identification of microsporidia causing human disease. J. Eukary. Microbiol. 43, 104S–105S (1996). (10.1111/j.1550-7408.1996.tb05026.x) / J. Eukary. Microbiol. by WS Hollister (1996)
Watson, A. K. et al. Transcriptomic profiling of host-parasite interactions in the microsporidian Trachipleistophora hominis. BMC Genomics 16, 983 (2015). (10.1186/s12864-015-1989-z) / BMC Genomics by AK Watson (2015)
Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013). (10.1186/gb-2013-14-4-r36) / Genome Biol. by D Kim (2013)
Edgar, R. C. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5, 113 (2004). (10.1186/1471-2105-5-113) / BMC Bioinformatics by RC Edgar (2004)
Le, S. Q. & Gascuel, O. An improved general amino acid replacement matrix. Mol. Biol. Evol. 25, 1307–1320 (2008). (10.1093/molbev/msn067) / Mol. Biol. Evol. by SQ Le (2008)
Lartillot, N. & Philippe, H. A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process. Mol. Biol. Evol. 21, 1095–1109 (2004). (10.1093/molbev/msh112) / Mol. Biol. Evol. by N Lartillot (2004)
Lartillot, N., Brinkmann, H. & Philippe, H. Suppression of long-branch attraction artefacts in the animal phylogeny using a site-heterogeneous model. BMC Evol. Biol. 7, S4 (2007). (10.1186/1471-2148-7-S1-S4) / BMC Evol. Biol. by N Lartillot (2007)
Soding, J., Biegert, A. & Lupas, A. N. The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res. 33, W244–W248 (2005). (10.1093/nar/gki408) / Nucleic Acids Res. by J Soding (2005)

Dates

Type	When
Created	7 years, 4 months ago (April 23, 2018, 11:38 a.m.)
Deposited	2 years, 8 months ago (Dec. 20, 2022, 8:52 a.m.)
Indexed	3 days, 7 hours ago (Aug. 26, 2025, 2:55 a.m.)
Issued	7 years, 4 months ago (April 27, 2018)
Published	7 years, 4 months ago (April 27, 2018)
Published Online	7 years, 4 months ago (April 27, 2018)

Funders 0

None

BibTeX

@article{Dean_2018, title={Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasites}, volume={9}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/s41467-018-03923-4}, DOI={10.1038/s41467-018-03923-4}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Dean, P. and Sendra, K. M. and Williams, T. A. and Watson, A. K. and Major, P. and Nakjang, S. and Kozhevnikova, E. and Goldberg, A. V. and Kunji, E. R. S. and Hirt, R. P. and Embley, T. M.}, year={2018}, month=apr }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        26
      ]
    ],
    "date-time": "2025-08-26T06:55:59Z",
    "timestamp": 1756191359962,
    "version": "3.37.3"
  },
  "reference-count": 46,
  "publisher": "Springer Science and Business Media LLC",
  "issue": "1",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2018,
            4,
            27
          ]
        ],
        "date-time": "2018-04-27T00:00:00Z",
        "timestamp": 1524787200000
      },
      "content-version": "tdm",
      "delay-in-days": 0,
      "URL": "https://creativecommons.org/licenses/by/4.0"
    },
    {
      "start": {
        "date-parts": [
          [
            2018,
            4,
            27
          ]
        ],
        "date-time": "2018-04-27T00:00:00Z",
        "timestamp": 1524787200000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "https://creativecommons.org/licenses/by/4.0"
    }
  ],
  "content-domain": {
    "domain": [
      "link.springer.com"
    ],
    "crossmark-restriction": false
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>The acquisition of genes by horizontal transfer can impart entirely new biological functions and provide an important route to major evolutionary innovation. Here we have used ancient gene reconstruction and functional assays to investigate the impact of a single horizontally transferred nucleotide transporter into the common ancestor of the Microsporidia, a major radiation of intracellular parasites of animals and humans. We show that this transporter provided early microsporidians with the ability to steal host ATP and to become energy parasites. Gene duplication enabled the diversification of nucleotide transporter function to transport new substrates, including GTP and NAD<jats:sup>+</jats:sup>, and to evolve the proton-energized net import of nucleotides for nucleic acid biosynthesis, growth and replication. These innovations have allowed the loss of pathways for mitochondrial and cytosolic energy generation and nucleotide biosynthesis that are otherwise essential for free-living eukaryotes, resulting in the highly unusual and reduced cells and genomes of contemporary Microsporidia.</jats:p>",
  "DOI": "10.1038/s41467-018-03923-4",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2018,
        4,
        23
      ]
    ],
    "date-time": "2018-04-23T15:38:13Z",
    "timestamp": 1524497893000
  },
  "update-policy": "https://doi.org/10.1007/springer_crossmark_policy",
  "source": "Crossref",
  "is-referenced-by-count": 83,
  "title": "Transporter gene acquisition and innovation in the evolution of Microsporidia intracellular parasites",
  "prefix": "10.1038",
  "volume": "9",
  "author": [
    {
      "given": "P.",
      "family": "Dean",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "K. M.",
      "family": "Sendra",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "ORCID": "https://orcid.org/0000-0003-1072-0223",
      "authenticated-orcid": false,
      "given": "T. A.",
      "family": "Williams",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "A. K.",
      "family": "Watson",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "P.",
      "family": "Major",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "S.",
      "family": "Nakjang",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "E.",
      "family": "Kozhevnikova",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "A. V.",
      "family": "Goldberg",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "E. R. S.",
      "family": "Kunji",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "R. P.",
      "family": "Hirt",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "ORCID": "https://orcid.org/0000-0002-1484-340X",
      "authenticated-orcid": false,
      "given": "T. M.",
      "family": "Embley",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "297",
  "published-online": {
    "date-parts": [
      [
        2018,
        4,
        27
      ]
    ]
  },
  "reference": [
    {
      "key": "3923_CR1",
      "doi-asserted-by": "publisher",
      "first-page": "490",
      "DOI": "10.1097/QCO.0b013e32834aa152",
      "volume": "24",
      "author": "ES Didier",
      "year": "2011",
      "unstructured": "Didier, E. S. & Weiss, L. M. Microsporidiosis: not just in AIDS patients. Curr. Opin. Infect. Dis. 24, 490\u2013495 (2011).",
      "journal-title": "Curr. Opin. Infect. Dis."
    },
    {
      "key": "3923_CR2",
      "doi-asserted-by": "publisher",
      "first-page": "336",
      "DOI": "10.1016/j.pt.2015.12.004",
      "volume": "32",
      "author": "GD Stentiford",
      "year": "2016",
      "unstructured": "Stentiford, G. D. et al. Microsporidia - emergent pathogens in the global food chain. Trends Parasitol. 32, 336\u2013348 (2016).",
      "journal-title": "Trends Parasitol."
    },
    {
      "key": "3923_CR3",
      "doi-asserted-by": "publisher",
      "first-page": "253",
      "DOI": "10.1016/B978-0-12-407706-5.00004-6",
      "volume": "82",
      "author": "J Vavra",
      "year": "2013",
      "unstructured": "Vavra, J. & Lukes, J. Microsporidia and \u2018the art of living together\u2019. Adv. Parasitol. 82, 253\u2013319 (2013).",
      "journal-title": "Adv. Parasitol."
    },
    {
      "key": "3923_CR4",
      "doi-asserted-by": "publisher",
      "first-page": "450",
      "DOI": "10.1038/35106579",
      "volume": "414",
      "author": "MD Katinka",
      "year": "2001",
      "unstructured": "Katinka, M. D. et al. Genome sequence and gene compaction of the eukaryote parasite Encephalitozoon cuniculi. Nature 414, 450\u2013453 (2001).",
      "journal-title": "Nature"
    },
    {
      "key": "3923_CR5",
      "doi-asserted-by": "publisher",
      "first-page": "304",
      "DOI": "10.1093/gbe/evq022",
      "volume": "2",
      "author": "PJ Keeling",
      "year": "2010",
      "unstructured": "Keeling, P. J. et al. The reduced genome of the parasitic microsporidian Enterocytozoon bieneusi lacks genes for core carbon metabolism. Genome Biol. Evol. 2, 304\u2013309 (2010).",
      "journal-title": "Genome Biol. Evol."
    },
    {
      "key": "3923_CR6",
      "doi-asserted-by": "publisher",
      "first-page": "e1002979",
      "DOI": "10.1371/journal.ppat.1002979",
      "volume": "8",
      "author": "E Heinz",
      "year": "2012",
      "unstructured": "Heinz, E. et al. The genome of the obligate intracellular parasite Trachipleistophora hominis: new insights into microsporidian genome dynamics and reductive evolution. PLoS Pathog. 8, e1002979 (2012).",
      "journal-title": "PLoS Pathog."
    },
    {
      "key": "3923_CR7",
      "doi-asserted-by": "publisher",
      "first-page": "865",
      "DOI": "10.1038/nature00949",
      "volume": "418",
      "author": "BA Williams",
      "year": "2002",
      "unstructured": "Williams, B. A., Hirt, R. P., Lucocq, J. M. & Embley, T. M. A mitochondrial remnant in the microsporidian Trachipleistophora hominis. Nature 418, 865\u2013869 (2002).",
      "journal-title": "Nature"
    },
    {
      "key": "3923_CR8",
      "doi-asserted-by": "publisher",
      "first-page": "624",
      "DOI": "10.1038/nature06606",
      "volume": "452",
      "author": "AV Goldberg",
      "year": "2008",
      "unstructured": "Goldberg, A. V. et al. Localization and functionality of microsporidian iron-sulphur cluster assembly proteins. Nature 452, 624\u2013628 (2008).",
      "journal-title": "Nature"
    },
    {
      "key": "3923_CR9",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/ncomms13932",
      "volume": "8",
      "author": "SA Freibert",
      "year": "2017",
      "unstructured": "Freibert, S. A. et al. Evolutionary conservation and in vitro reconstitution of microsporidian iron-sulfur cluster biosynthesis. Nat. Commun. 8, 13932 (2017).",
      "journal-title": "Nat. Commun."
    },
    {
      "key": "3923_CR10",
      "doi-asserted-by": "publisher",
      "first-page": "588",
      "DOI": "10.1128/EC.00283-10",
      "volume": "10",
      "author": "VV Dolgikh",
      "year": "2011",
      "unstructured": "Dolgikh, V. V., Senderskiy, I. V., Pavlova, O. A., Naumov, A. M. & Beznoussenko, G. V. Immunolocalization of an alternative respiratory chain in Antonospora (Paranosema) locustae spores: mitosomes retain their role in microsporidial energy metabolism. Eukaryot. Cell. 10, 588\u2013593 (2011).",
      "journal-title": "Eukaryot. Cell."
    },
    {
      "key": "3923_CR11",
      "doi-asserted-by": "publisher",
      "first-page": "2077",
      "DOI": "10.1111/1462-2920.13734",
      "volume": "19",
      "author": "D Wiredu Boakye",
      "year": "2017",
      "unstructured": "Wiredu Boakye, D. et al. Decay of the glycolytic pathway and adaptation to intranuclear parasitism within Enterocytozoonidae microsporidia. Environ. Microbiol. 19, 2077\u20132089 (2017).",
      "journal-title": "Environ. Microbiol."
    },
    {
      "key": "3923_CR12",
      "doi-asserted-by": "publisher",
      "first-page": "21465",
      "DOI": "10.1073/pnas.0907732106",
      "volume": "106",
      "author": "R Phillips",
      "year": "2009",
      "unstructured": "Phillips, R. & Milo, R. A feeling for the numbers in biology. Proc. Natl Acad. Sci. USA 106, 21465\u201321471 (2009).",
      "journal-title": "Proc. Natl Acad. Sci. USA"
    },
    {
      "key": "3923_CR13",
      "doi-asserted-by": "publisher",
      "first-page": "2285",
      "DOI": "10.1093/gbe/evt184",
      "volume": "5",
      "author": "S Nakjang",
      "year": "2013",
      "unstructured": "Nakjang, S. et al. Reduction and expansion in microsporidian genome evolution: new insights from comparative genomics. Genome Biol. Evol. 5, 2285\u20132303 (2013).",
      "journal-title": "Genome Biol. Evol."
    },
    {
      "key": "3923_CR14",
      "doi-asserted-by": "publisher",
      "first-page": "553",
      "DOI": "10.1038/nature06903",
      "volume": "453",
      "author": "AD Tsaousis",
      "year": "2008",
      "unstructured": "Tsaousis, A. D. et al. A novel route for ATP acquisition by the remnant mitochondria of Encephalitozoon cuniculi. Nature 453, 553\u2013556 (2008).",
      "journal-title": "Nature"
    },
    {
      "key": "3923_CR15",
      "doi-asserted-by": "publisher",
      "first-page": "e1004547",
      "DOI": "10.1371/journal.ppat.1004547",
      "volume": "10",
      "author": "E Heinz",
      "year": "2014",
      "unstructured": "Heinz, E. et al. Plasma membrane-located purine nucleotide transport proteins are key components for host exploitation by microsporidian intracellular parasites. PLoS Pathog. 10, e1004547 (2014).",
      "journal-title": "PLoS Pathog."
    },
    {
      "key": "3923_CR16",
      "doi-asserted-by": "publisher",
      "first-page": "17",
      "DOI": "10.1078/143446103764928468",
      "volume": "154",
      "author": "TA Richards",
      "year": "2003",
      "unstructured": "Richards, T. A., Hirt, R. P., Williams, B. A. & Embley, T. M. Horizontal gene transfer and the evolution of parasitic protozoa. Protist 154, 17\u201332 (2003).",
      "journal-title": "Protist"
    },
    {
      "key": "3923_CR17",
      "doi-asserted-by": "publisher",
      "first-page": "1548",
      "DOI": "10.1016/j.cub.2013.06.057",
      "volume": "23",
      "author": "TY James",
      "year": "2013",
      "unstructured": "James, T. Y. et al. Shared signatures of parasitism and phylogenomics unite cryptomycota and microsporidia. Curr. Biol. 23, 1548\u20131553 (2013).",
      "journal-title": "Curr. Biol."
    },
    {
      "key": "3923_CR18",
      "doi-asserted-by": "publisher",
      "first-page": "480",
      "DOI": "10.1093/gbe/evx015",
      "volume": "9",
      "author": "P Major",
      "year": "2017",
      "unstructured": "Major, P., Embley, T. M. & Williams, T. A. Phylogenetic diversity of NTT nucleotide transport proteins in free-living and parasitic bacteria and eukaryotes. Genome Biol. Evol. 9, 480\u2013487 (2017).",
      "journal-title": "Genome Biol. Evol."
    },
    {
      "key": "3923_CR19",
      "doi-asserted-by": "publisher",
      "first-page": "e29594",
      "DOI": "10.7554/eLife.29594",
      "volume": "6",
      "author": "CA Quandt",
      "year": "2017",
      "unstructured": "Quandt, C. A. et al. The genome of an intranuclear parasite, Paramicrosporidium saccamoebae, reveals alternative adaptations to obligate intracellular parasitism. eLife 6, e29594 (2017).",
      "journal-title": "eLife"
    },
    {
      "key": "3923_CR20",
      "doi-asserted-by": "publisher",
      "first-page": "15480",
      "DOI": "10.1073/pnas.1410442111",
      "volume": "111",
      "author": "KL Haag",
      "year": "2014",
      "unstructured": "Haag, K. L. et al. Evolution of a morphological novelty occurred before genome compaction in a lineage of extreme parasites. Proc. Natl Acad. Sci. USA 111, 15480\u201315485 (2014).",
      "journal-title": "Proc. Natl Acad. Sci. USA"
    },
    {
      "key": "3923_CR21",
      "doi-asserted-by": "publisher",
      "first-page": "9",
      "DOI": "10.1002/bies.201300095",
      "volume": "36",
      "author": "G Schonknecht",
      "year": "2014",
      "unstructured": "Schonknecht, G., Weber, A. P. & Lercher, M. J. Horizontal gene acquisitions by eukaryotes as drivers of adaptive evolution. Bioessays 36, 9\u201320 (2014).",
      "journal-title": "Bioessays"
    },
    {
      "key": "3923_CR22",
      "doi-asserted-by": "publisher",
      "first-page": "366",
      "DOI": "10.1038/nrg1324",
      "volume": "5",
      "author": "JW Thornton",
      "year": "2004",
      "unstructured": "Thornton, J. W. Resurrecting ancient genes: experimental analysis of extinct molecules. Nat. Rev. Genet. 5, 366\u2013375 (2004).",
      "journal-title": "Nat. Rev. Genet."
    },
    {
      "key": "3923_CR23",
      "doi-asserted-by": "publisher",
      "first-page": "2286",
      "DOI": "10.1093/bioinformatics/btp368",
      "volume": "25",
      "author": "N Lartillot",
      "year": "2009",
      "unstructured": "Lartillot, N., Lepage, T. & Blanquart, S. PhyloBayes 3: a Bayesian software package for phylogenetic reconstruction and molecular dating. Bioinformatics 25, 2286\u20132288 (2009).",
      "journal-title": "Bioinformatics"
    },
    {
      "key": "3923_CR24",
      "doi-asserted-by": "publisher",
      "first-page": "4098",
      "DOI": "10.1046/j.1432-1033.2000.01468.x",
      "volume": "267",
      "author": "O Trentmann",
      "year": "2000",
      "unstructured": "Trentmann, O., Decker, C., Winkler, H. H. & Neuhaus, H. E. Charged amino-acid residues in transmembrane domains of the plastidic ATP/ADP transporter from Arabidopsis are important for transport efficiency, substrate specificity, and counter exchange properties. Eur. J. Biochem. 267, 4098\u20134105 (2000).",
      "journal-title": "Eur. J. Biochem."
    },
    {
      "key": "3923_CR25",
      "doi-asserted-by": "publisher",
      "first-page": "849",
      "DOI": "10.1093/bioinformatics/17.9.849",
      "volume": "17",
      "author": "GE Tusnady",
      "year": "2001",
      "unstructured": "Tusnady, G. E. & Simon, I. The HMMTOP transmembrane topology prediction server. Bioinformatics 17, 849\u2013850 (2001).",
      "journal-title": "Bioinformatics"
    },
    {
      "key": "3923_CR26",
      "doi-asserted-by": "publisher",
      "first-page": "123",
      "DOI": "10.1038/nrm.2015.25",
      "volume": "17",
      "author": "EM Quistgaard",
      "year": "2016",
      "unstructured": "Quistgaard, E. M., Low, C., Guettou, F. & Nordlund, P. Understanding transport by the major facilitator superfamily (MFS): structures pave the way. Nat. Rev. Mol. Cell. Biol. 17, 123\u2013132 (2016).",
      "journal-title": "Nat. Rev. Mol. Cell. Biol."
    },
    {
      "key": "3923_CR27",
      "doi-asserted-by": "publisher",
      "first-page": "1534",
      "DOI": "10.1111/j.1365-2958.2006.05193.x",
      "volume": "60",
      "author": "I Haferkamp",
      "year": "2006",
      "unstructured": "Haferkamp, I. et al. Tapping the nucleotide pool of the host: novel nucleotide carrier proteins of Protochlamydia amoebophila. Mol. Microbiol. 60, 1534\u20131545 (2006).",
      "journal-title": "Mol. Microbiol."
    },
    {
      "key": "3923_CR28",
      "doi-asserted-by": "crossref",
      "unstructured": "Ohno, S. Evolution by Gene Duplication. (Springer-Verlag, Berlin, Heidelberg, 1970).",
      "DOI": "10.1007/978-3-642-86659-3"
    },
    {
      "key": "3923_CR29",
      "doi-asserted-by": "publisher",
      "first-page": "e1005870",
      "DOI": "10.1371/journal.ppat.1005870",
      "volume": "12",
      "author": "P Dean",
      "year": "2016",
      "unstructured": "Dean, P., Hirt, R. P. & Embley, T. M. Microsporidia: why make nucleotides if you can steal them? PLoS Pathog. 12, e1005870 (2016).",
      "journal-title": "PLoS Pathog."
    },
    {
      "key": "3923_CR30",
      "doi-asserted-by": "publisher",
      "first-page": "61",
      "DOI": "10.1016/j.actatropica.2005.01.010",
      "volume": "94",
      "author": "ES Didier",
      "year": "2005",
      "unstructured": "Didier, E. S. Microsporidiosis: an emerging and opportunistic infection in humans and animals. Acta Trop. 94, 61\u201376 (2005).",
      "journal-title": "Acta Trop."
    },
    {
      "key": "3923_CR31",
      "doi-asserted-by": "publisher",
      "first-page": "1",
      "DOI": "10.1007/BF00928361",
      "volume": "140",
      "author": "TW Traut",
      "year": "1994",
      "unstructured": "Traut, T. W. Physiological concentrations of purines and pyrimidines. Mol. Cell. Biochem. 140, 1\u201322 (1994).",
      "journal-title": "Mol. Cell. Biochem."
    },
    {
      "key": "3923_CR32",
      "doi-asserted-by": "publisher",
      "first-page": "622",
      "DOI": "10.1038/nature03131",
      "volume": "432",
      "author": "I Haferkamp",
      "year": "2004",
      "unstructured": "Haferkamp, I. et al. A candidate NAD+transporter in an intracellular bacterial symbiont related to Chlamydiae. Nature 432, 622\u2013625 (2004).",
      "journal-title": "Nature"
    },
    {
      "key": "3923_CR33",
      "doi-asserted-by": "publisher",
      "first-page": "2478",
      "DOI": "10.1101/gr.142802.112",
      "volume": "22",
      "author": "CA Cuomo",
      "year": "2012",
      "unstructured": "Cuomo, C. A. et al. Microsporidian genome analysis reveals evolutionary strategies for obligate intracellular growth. Genome Res. 22, 2478\u20132488 (2012).",
      "journal-title": "Genome Res."
    },
    {
      "key": "3923_CR34",
      "doi-asserted-by": "publisher",
      "first-page": "617",
      "DOI": "10.1038/nature02424",
      "volume": "428",
      "author": "M Kellis",
      "year": "2004",
      "unstructured": "Kellis, M., Birren, B. W. & Lander, E. S. Proof and evolutionary analysis of ancient genome duplication in the yeast Saccharomyces cerevisiae. Nature 428, 617\u2013624 (2004).",
      "journal-title": "Nature"
    },
    {
      "key": "3923_CR35",
      "doi-asserted-by": "publisher",
      "first-page": "437",
      "DOI": "10.1016/S0968-0004(99)01460-7",
      "volume": "24",
      "author": "JR Warner",
      "year": "1999",
      "unstructured": "Warner, J. R. The economics of ribosome biosynthesis in yeast. Trends Biochem. Sci. 24, 437\u2013440 (1999).",
      "journal-title": "Trends Biochem. Sci."
    },
    {
      "key": "3923_CR36",
      "doi-asserted-by": "publisher",
      "first-page": "1590",
      "DOI": "10.1093/gbe/evv090",
      "volume": "7",
      "author": "Y Chang",
      "year": "2015",
      "unstructured": "Chang, Y. et al. Phylogenomic analyses Indicate that early fungi evolved digesting cell walls of algal ancestors of land plants. Genome Biol. Evol. 7, 1590\u20131601 (2015).",
      "journal-title": "Genome Biol. Evol."
    },
    {
      "key": "3923_CR37",
      "doi-asserted-by": "crossref",
      "unstructured": "Sebe-Pedros, A., Degnan, B. M. & Ruiz-Trillo, I. The origin of Metazoa: a unicellular perspective. Nat. Rev. Genet. 18, 498\u2013512 (2017).",
      "DOI": "10.1038/nrg.2017.21"
    },
    {
      "key": "3923_CR38",
      "doi-asserted-by": "crossref",
      "first-page": "2803",
      "DOI": "10.1128/jcm.34.11.2803-2811.1996",
      "volume": "34",
      "author": "AS Field",
      "year": "1996",
      "unstructured": "Field, A. S. et al. Myositis associated with a newly described microsporidian, Trachipleistophora hominis, in a patint with AIDS. J. Clin. Microbiol. 34, 2803\u20132811 (1996).",
      "journal-title": "J. Clin. Microbiol."
    },
    {
      "key": "3923_CR39",
      "doi-asserted-by": "publisher",
      "first-page": "104S",
      "DOI": "10.1111/j.1550-7408.1996.tb05026.x",
      "volume": "43",
      "author": "WS Hollister",
      "year": "1996",
      "unstructured": "Hollister, W. S., Canning, E. U. & Anderson, C. L. Identification of microsporidia causing human disease. J. Eukary. Microbiol. 43, 104S\u2013105S (1996).",
      "journal-title": "J. Eukary. Microbiol."
    },
    {
      "key": "3923_CR40",
      "doi-asserted-by": "publisher",
      "DOI": "10.1186/s12864-015-1989-z",
      "volume": "16",
      "author": "AK Watson",
      "year": "2015",
      "unstructured": "Watson, A. K. et al. Transcriptomic profiling of host-parasite interactions in the microsporidian Trachipleistophora hominis. BMC Genomics 16, 983 (2015).",
      "journal-title": "BMC Genomics"
    },
    {
      "key": "3923_CR41",
      "doi-asserted-by": "publisher",
      "DOI": "10.1186/gb-2013-14-4-r36",
      "volume": "14",
      "author": "D Kim",
      "year": "2013",
      "unstructured": "Kim, D. et al. TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biol. 14, R36 (2013).",
      "journal-title": "Genome Biol."
    },
    {
      "key": "3923_CR42",
      "doi-asserted-by": "publisher",
      "DOI": "10.1186/1471-2105-5-113",
      "volume": "5",
      "author": "RC Edgar",
      "year": "2004",
      "unstructured": "Edgar, R. C. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5, 113 (2004).",
      "journal-title": "BMC Bioinformatics"
    },
    {
      "key": "3923_CR43",
      "doi-asserted-by": "publisher",
      "first-page": "1307",
      "DOI": "10.1093/molbev/msn067",
      "volume": "25",
      "author": "SQ Le",
      "year": "2008",
      "unstructured": "Le, S. Q. & Gascuel, O. An improved general amino acid replacement matrix. Mol. Biol. Evol. 25, 1307\u20131320 (2008).",
      "journal-title": "Mol. Biol. Evol."
    },
    {
      "key": "3923_CR44",
      "doi-asserted-by": "publisher",
      "first-page": "1095",
      "DOI": "10.1093/molbev/msh112",
      "volume": "21",
      "author": "N Lartillot",
      "year": "2004",
      "unstructured": "Lartillot, N. & Philippe, H. A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process. Mol. Biol. Evol. 21, 1095\u20131109 (2004).",
      "journal-title": "Mol. Biol. Evol."
    },
    {
      "key": "3923_CR45",
      "doi-asserted-by": "publisher",
      "first-page": "S4",
      "DOI": "10.1186/1471-2148-7-S1-S4",
      "volume": "7",
      "author": "N Lartillot",
      "year": "2007",
      "unstructured": "Lartillot, N., Brinkmann, H. & Philippe, H. Suppression of long-branch attraction artefacts in the animal phylogeny using a site-heterogeneous model. BMC Evol. Biol. 7, S4 (2007).",
      "journal-title": "BMC Evol. Biol."
    },
    {
      "key": "3923_CR46",
      "doi-asserted-by": "publisher",
      "first-page": "W244",
      "DOI": "10.1093/nar/gki408",
      "volume": "33",
      "author": "J Soding",
      "year": "2005",
      "unstructured": "Soding, J., Biegert, A. & Lupas, A. N. The HHpred interactive server for protein homology detection and structure prediction. Nucleic Acids Res. 33, W244\u2013W248 (2005).",
      "journal-title": "Nucleic Acids Res."
    }
  ],
  "container-title": "Nature Communications",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.nature.com/articles/s41467-018-03923-4.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://www.nature.com/articles/s41467-018-03923-4",
      "content-type": "text/html",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://www.nature.com/articles/s41467-018-03923-4.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2022,
        12,
        20
      ]
    ],
    "date-time": "2022-12-20T13:52:26Z",
    "timestamp": 1671544346000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.nature.com/articles/s41467-018-03923-4"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2018,
        4,
        27
      ]
    ]
  },
  "references-count": 46,
  "journal-issue": {
    "issue": "1",
    "published-online": {
      "date-parts": [
        [
          2018,
          12
        ]
      ]
    }
  },
  "alternative-id": [
    "3923"
  ],
  "URL": "http://dx.doi.org/10.1038/s41467-018-03923-4",
  "relation": {},
  "ISSN": [
    "2041-1723"
  ],
  "subject": [],
  "container-title-short": "Nat Commun",
  "published": {
    "date-parts": [
      [
        2018,
        4,
        27
      ]
    ]
  },
  "assertion": [
    {
      "value": "27 November 2017",
      "order": 1,
      "name": "received",
      "label": "Received",
      "group": {
        "name": "ArticleHistory",
        "label": "Article History"
      }
    },
    {
      "value": "22 March 2018",
      "order": 2,
      "name": "accepted",
      "label": "Accepted",
      "group": {
        "name": "ArticleHistory",
        "label": "Article History"
      }
    },
    {
      "value": "27 April 2018",
      "order": 3,
      "name": "first_online",
      "label": "First Online",
      "group": {
        "name": "ArticleHistory",
        "label": "Article History"
      }
    },
    {
      "value": "The authors declare no competing interests.",
      "order": 1,
      "name": "Ethics",
      "group": {
        "name": "EthicsHeading",
        "label": "Competing interests"
      }
    }
  ],
  "article-number": "1709"
}