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Genomics of Loa loa, a Wolbachia-free filarial parasite of humans

Identifieur interne : 004707 ( Pmc/Curation ); précédent : 004706; suivant : 004708

Genomics of Loa loa, a Wolbachia-free filarial parasite of humans

Auteurs : Christopher A. Desjardins [États-Unis] ; Gustavo C. Cerqueira [États-Unis] ; Jonathan M. Goldberg [États-Unis] ; Julie C. Dunning Hotopp [États-Unis] ; Brian J. Haas [États-Unis] ; Jeremy Zucker [États-Unis] ; Jose M. C. Ribeiro ; Sakina Saif [États-Unis] ; Joshua Z. Levin [États-Unis] ; Lin Fan [États-Unis] ; Qiandong Zeng [États-Unis] ; Carsten Russ [États-Unis] ; Jennifer R. Wortman [États-Unis] ; Doran L. Fink [États-Unis] ; Bruce W. Birren [États-Unis] ; Thomas B. Nutman [États-Unis]

Source :

RBID : PMC:4238225

Abstract

Loa loa, the African eyeworm, is a major filarial pathogen of humans. Unlike most filariae, Loa loa does not contain the obligate intracellular Wolbachia endosymbiont. We describe the 91.4 Mb genome of Loa loa, and the genome of the related filarial parasite Wuchereria bancrofti, and predict 14,907 Loa loa genes based on microfilarial RNA sequencing. By comparing these genomes to that of another filarial parasite, Brugia malayi, and to several other nematode genomes, we demonstrate synteny among filariae but not with non-parasitic nematodes. The Loa loa genome encodes many immunologically relevant genes, as well as protein kinases targeted by drugs currently approved for humans. Despite lacking Wolbachia, Loa loa shows no new metabolic synthesis or transport capabilities compared to other filariae. These results suggest that the role played by Wolbachia in filarial biology is more subtle than previously thought and reveal marked differences between parasitic and non-parasitic nematodes.


Url:
DOI: 10.1038/ng.2585
PubMed: 23525074
PubMed Central: 4238225

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PMC:4238225

Le document en format XML

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<p id="P2">
<italic>Loa loa</italic>
, the African eyeworm, is a major filarial pathogen of humans. Unlike most filariae,
<italic>Loa loa</italic>
does not contain the obligate intracellular
<italic>Wolbachia</italic>
endosymbiont. We describe the 91.4 Mb genome of
<italic>Loa loa</italic>
, and the genome of the related filarial parasite
<italic>Wuchereria bancrofti</italic>
, and predict 14,907
<italic>Loa loa</italic>
genes based on microfilarial RNA sequencing. By comparing these genomes to that of another filarial parasite,
<italic>Brugia malayi</italic>
, and to several other nematode genomes, we demonstrate synteny among filariae but not with non-parasitic nematodes. The
<italic>Loa loa</italic>
genome encodes many immunologically relevant genes, as well as protein kinases targeted by drugs currently approved for humans. Despite lacking
<italic>Wolbachia, Loa loa</italic>
shows no new metabolic synthesis or transport capabilities compared to other filariae. These results suggest that the role played by
<italic>Wolbachia</italic>
in filarial biology is more subtle than previously thought and reveal marked differences between parasitic and non-parasitic nematodes.</p>
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</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<pmc-dir>properties manuscript</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-journal-id">9216904</journal-id>
<journal-id journal-id-type="pubmed-jr-id">2419</journal-id>
<journal-id journal-id-type="nlm-ta">Nat Genet</journal-id>
<journal-id journal-id-type="iso-abbrev">Nat. Genet.</journal-id>
<journal-title-group>
<journal-title>Nature genetics</journal-title>
</journal-title-group>
<issn pub-type="ppub">1061-4036</issn>
<issn pub-type="epub">1546-1718</issn>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">23525074</article-id>
<article-id pub-id-type="pmc">4238225</article-id>
<article-id pub-id-type="doi">10.1038/ng.2585</article-id>
<article-id pub-id-type="manuscript">NIHMS474969</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Genomics of
<italic>Loa loa</italic>
, a
<italic>Wolbachia</italic>
-free filarial parasite of humans</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Desjardins</surname>
<given-names>Christopher A.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cerqueira</surname>
<given-names>Gustavo C.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Goldberg</surname>
<given-names>Jonathan M.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hotopp</surname>
<given-names>Julie C. Dunning</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Haas</surname>
<given-names>Brian J.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zucker</surname>
<given-names>Jeremy</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Ribeiro</surname>
<given-names>Jose’ M.C.</given-names>
</name>
<xref ref-type="aff" rid="A1">4</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Saif</surname>
<given-names>Sakina</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Levin</surname>
<given-names>Joshua Z.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fan</surname>
<given-names>Lin</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Zeng</surname>
<given-names>Qiandong</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Russ</surname>
<given-names>Carsten</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wortman</surname>
<given-names>Jennifer R.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Fink</surname>
<given-names>Doran L.</given-names>
</name>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Birren</surname>
<given-names>Bruce W.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Nutman</surname>
<given-names>Thomas B.</given-names>
</name>
<email>tnutman@niaid.nih.gov</email>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
</contrib-group>
<aff id="A1">
<label>1</label>
Broad Institute of MIT and Harvard, Cambridge, MA</aff>
<aff id="A2">
<label>2</label>
Institute for Genome Science, Department of Microbiology & Immunology, University of Maryland School of Medicine, Baltimore, MD</aff>
<aff id="A3">
<label>3</label>
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, MD</aff>
<aff id="A4">
<label>4</label>
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Bethesda, MD</aff>
<author-notes>
<fn id="FN1" fn-type="present-address">
<label>*</label>
<p id="P1">current address: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted">
<day>14</day>
<month>11</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub">
<day>24</day>
<month>3</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="ppub">
<month>5</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>20</day>
<month>11</month>
<year>2014</year>
</pub-date>
<volume>45</volume>
<issue>5</issue>
<fpage>495</fpage>
<lpage>500</lpage>
<pmc-comment>elocation-id from pubmed: 10.1038/ng.2585</pmc-comment>
<permissions>
<license>
<license-p>Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
<uri xlink:type="simple" xlink:href="http://www.nature.com/authors/editorial_policies/license.html#terms">http://www.nature.com/authors/editorial_policies/license.html#terms</uri>
</license-p>
</license>
</permissions>
<abstract>
<p id="P2">
<italic>Loa loa</italic>
, the African eyeworm, is a major filarial pathogen of humans. Unlike most filariae,
<italic>Loa loa</italic>
does not contain the obligate intracellular
<italic>Wolbachia</italic>
endosymbiont. We describe the 91.4 Mb genome of
<italic>Loa loa</italic>
, and the genome of the related filarial parasite
<italic>Wuchereria bancrofti</italic>
, and predict 14,907
<italic>Loa loa</italic>
genes based on microfilarial RNA sequencing. By comparing these genomes to that of another filarial parasite,
<italic>Brugia malayi</italic>
, and to several other nematode genomes, we demonstrate synteny among filariae but not with non-parasitic nematodes. The
<italic>Loa loa</italic>
genome encodes many immunologically relevant genes, as well as protein kinases targeted by drugs currently approved for humans. Despite lacking
<italic>Wolbachia, Loa loa</italic>
shows no new metabolic synthesis or transport capabilities compared to other filariae. These results suggest that the role played by
<italic>Wolbachia</italic>
in filarial biology is more subtle than previously thought and reveal marked differences between parasitic and non-parasitic nematodes.</p>
</abstract>
</article-meta>
</front>
<floats-group>
<fig id="F1" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<p id="P43">Synteny between filarial worms and
<italic>C. elegans</italic>
.
<bold>(A)</bold>
Gene distribution on the
<italic>C. elegans</italic>
genome. Black-edged vertical bars represent each one of the six
<italic>C. elegans</italic>
chromosomes, labeled accordingly in the bottommost part of the panel. Horizontal colored boxes within each bar indicate the location and strand of
<italic>C. elegans</italic>
genes (leftmost column = plus strand; rightmost column = minus strand). The color of the lines designates each chromosome and serves as a color-based legend for panel B;
<bold>(B)</bold>
Gene distribution on the twelve longest
<italic>L. loa</italic>
scaffolds. Scaffolds are represented by black-edged horizontal bars, and identified by labels on the left. Vertical colored boxes indicate the position and strand of each gene (uppermost column = plus strand; bottommost column = minus strand). The color-coding indicates the chromosome where each respective ortholog in
<italic>C. elegans</italic>
is located. Grey colored boxes represent either genes without orthologs in
<italic>C. elegans</italic>
or genes with two or more homologs in distinct
<italic>C. elegans</italic>
chromosomes;
<bold>(C)</bold>
Distribution of
<italic>L. loa</italic>
scaffold 4 orthologs on the
<italic>C. elegans W. bancrofti</italic>
and
<italic>B. malayi</italic>
genomes. The scaffolds and chromosomes with best matches to
<italic>L. loa</italic>
scaffold 4 based on whole genome alignment are depicted here. Each row contains one or more black-edged horizontal bars representing either chromosomes (
<italic>C. elegans</italic>
) or scaffolds (
<italic>L. loa B. malayi</italic>
and
<italic>W. bancrofti</italic>
) from each sequenced genome. Purple boxes indicate position and strand of genes. Grey projections connect orthologous genes across organisms.</p>
</caption>
<graphic xlink:href="nihms474969f1"></graphic>
</fig>
<fig id="F2" orientation="portrait" position="float">
<label>Figure 2</label>
<caption>
<p id="P44">Enriched and depleted PFAM and TIGRfam domains in each filarial genome relative to the other two. All domains significantly enriched (p < 0.05, Fisher’s exact test) are shown; red indicates enriched while blue indicates depleted. Numbers of identified domains are given in each box. Broad functional categories representing each domain are shown to the left.</p>
</caption>
<graphic xlink:href="nihms474969f2"></graphic>
</fig>
<fig id="F3" orientation="portrait" position="float">
<label>Figure 3</label>
<caption>
<p id="P45">Phylogenomic analysis of nematodes. Maximum likelihood, parsimony, and Bayesian methods all estimated an identical phylogeny using the concatenated protein sequences of 921 single copy orthologs. Adjacent to each node are likelihood bootstrap support values/parsimony bootstrap support values/Bayesian posterior probabilities. The distribution of genes in ortholog clusters is shown to the right of the phylogeny. Core genes are encoded by all genomes, shared genes are encoded by at least two but fewer than all genomes, and unique genes are found only in one genome. Orthologs specific to the non-parasitic nematodes (
<italic>C. elegans C. briggsae</italic>
, and
<italic>P. pacificus</italic>
) and filarial nematodes are also highlighted. Of the 6,280
<italic>L. loa</italic>
genes with no functional assignment, 3,665 are unique to
<italic>L. loa</italic>
and 1,158 are filaria-specific.</p>
</caption>
<graphic xlink:href="nihms474969f3"></graphic>
</fig>
<fig id="F4" orientation="portrait" position="float">
<label>Figure 4</label>
<caption>
<p id="P46">Phylogenetic profile of chemoreceptors in nematode genomes. Both the 7 transmembrane domain G-protein-coupled chemoreceptors (GPCRs) and guanylate and adenylate cyclases are shown.</p>
</caption>
<graphic xlink:href="nihms474969f4"></graphic>
</fig>
<table-wrap id="T1" position="float" orientation="landscape">
<label>Table 1</label>
<caption>
<p id="P47">Genome features of filarial worms and their
<italic>Wolbachia</italic>
endosymbionts;
<italic>Wolbachia</italic>
genome abbreviations stand for
<italic>Wolbachia</italic>
of
<italic>B. malayi</italic>
(
<italic>wBm</italic>
),
<italic>Wolbachia</italic>
of
<italic>W. bancrofti</italic>
(
<italic>wWb</italic>
), and
<italic>Wolbachia</italic>
of
<italic>O. volvulus</italic>
(
<italic>wOv</italic>
).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="middle" rowspan="1" colspan="1">Organism</th>
<th align="center" valign="middle" rowspan="1" colspan="1">Coverage</th>
<th align="left" valign="middle" rowspan="1" colspan="1">Sequence
<break></break>
(Mb)</th>
<th align="left" valign="middle" rowspan="1" colspan="1">Scaffolds</th>
<th align="left" valign="middle" rowspan="1" colspan="1">Scaffold N50
<break></break>
(Kb)</th>
<th align="center" valign="middle" rowspan="1" colspan="1">% GC</th>
<th align="left" valign="middle" rowspan="1" colspan="1">% Repetitive</th>
<th align="left" valign="middle" rowspan="1" colspan="1">% Low
<break></break>
Complexity</th>
<th align="left" valign="middle" rowspan="1" colspan="1"># of Genes</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">
<italic>L. loa</italic>
</td>
<td align="center" rowspan="1" colspan="1">20x</td>
<td align="center" rowspan="1" colspan="1">91.4</td>
<td align="left" rowspan="1" colspan="1">5774</td>
<td align="left" rowspan="1" colspan="1">172</td>
<td align="center" rowspan="1" colspan="1">31.0</td>
<td align="left" rowspan="1" colspan="1">9.3</td>
<td align="left" rowspan="1" colspan="1">1.7</td>
<td align="left" rowspan="1" colspan="1">14907
<xref ref-type="table-fn" rid="TFN1">a</xref>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<italic>W. bancrofti</italic>
</td>
<td align="center" rowspan="1" colspan="1">12x</td>
<td align="center" rowspan="1" colspan="1">81.5</td>
<td align="left" rowspan="1" colspan="1">25884</td>
<td align="left" rowspan="1" colspan="1">5.16</td>
<td align="center" rowspan="1" colspan="1">29.7</td>
<td align="left" rowspan="1" colspan="1">6.2</td>
<td align="left" rowspan="1" colspan="1">3.9</td>
<td align="left" rowspan="1" colspan="1">19327
<xref ref-type="table-fn" rid="TFN1">a</xref>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<italic>O. volvulus</italic>
</td>
<td align="center" rowspan="1" colspan="1">5x</td>
<td align="center" rowspan="1" colspan="1">26.0</td>
<td align="left" rowspan="1" colspan="1">22675</td>
<td align="left" rowspan="1" colspan="1">1.27</td>
<td align="center" rowspan="1" colspan="1">32.5</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="left" rowspan="1" colspan="1">--</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<italic>B. malayi</italic>
</td>
<td align="center" rowspan="1" colspan="1">9x</td>
<td align="center" rowspan="1" colspan="1">93.7</td>
<td align="left" rowspan="1" colspan="1">8180</td>
<td align="left" rowspan="1" colspan="1">94</td>
<td align="center" rowspan="1" colspan="1">30.2</td>
<td align="left" rowspan="1" colspan="1">12.1</td>
<td align="left" rowspan="1" colspan="1">1.1</td>
<td align="left" rowspan="1" colspan="1">18348</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<italic>wBm</italic>
</td>
<td align="center" rowspan="1" colspan="1">11x</td>
<td align="center" rowspan="1" colspan="1">1.08</td>
<td align="left" rowspan="1" colspan="1">1</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="center" rowspan="1" colspan="1">34.2</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="left" rowspan="1" colspan="1">805</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<italic>wWb</italic>
</td>
<td align="center" rowspan="1" colspan="1">2x</td>
<td align="center" rowspan="1" colspan="1">1.05</td>
<td align="left" rowspan="1" colspan="1">763</td>
<td align="left" rowspan="1" colspan="1">1.62</td>
<td align="center" rowspan="1" colspan="1">34.0</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="left" rowspan="1" colspan="1">--</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">
<italic>wOv</italic>
</td>
<td align="center" rowspan="1" colspan="1">2x</td>
<td align="center" rowspan="1" colspan="1">0.44</td>
<td align="left" rowspan="1" colspan="1">341</td>
<td align="left" rowspan="1" colspan="1">1.51</td>
<td align="center" rowspan="1" colspan="1">32.8</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="left" rowspan="1" colspan="1">--</td>
<td align="left" rowspan="1" colspan="1">--</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN1">
<label>a</label>
<p id="P48">Due to fragmentation of the genome assemblies, the true
<italic>W. bancrofti</italic>
gene count is estimated to be 14,496–15,075 genes, while the true
<italic>L. loa</italic>
gene count is estimated to be 14,261 genes (
<xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>
).</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T2" position="float" orientation="landscape">
<label>Table 2</label>
<caption>
<p id="P49">Phylogenetic profiles of biosynthesis pathways hypothesized to be involved in the Filaria-
<italic>Wolbachia</italic>
symbiosis. Conservation each pathway across nematodes and
<italic>Wolbachia</italic>
are shown in
<xref ref-type="supplementary-material" rid="SD1">Supplementary Tables 24 and 25</xref>
, respectively. Pathways are labeled as complete (+), partial (+/–), or absent (–);
<italic>Wolbachia</italic>
genome abbreviations stand for
<italic>Wolbachia</italic>
of
<italic>B. malayi</italic>
(
<italic>wBm</italic>
),
<italic>Wolbachia</italic>
of
<italic>D. melanogaster</italic>
(
<italic>wMel</italic>
),
<italic>Wolbachia</italic>
of
<italic>C. pipiens</italic>
(
<italic>wPip</italic>
) and
<italic>Wolbachia</italic>
of
<italic>W. bancrofti</italic>
(
<italic>wWb</italic>
).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="middle" rowspan="1" colspan="1">Biosynthesis
<break></break>
Pathway</th>
<th align="center" valign="middle" rowspan="1" colspan="1">C. elegans</th>
<th align="center" valign="middle" rowspan="1" colspan="1">C. briggsae</th>
<th align="center" valign="middle" rowspan="1" colspan="1">P. pacificus</th>
<th align="center" valign="middle" rowspan="1" colspan="1">M. hapla</th>
<th align="center" valign="middle" rowspan="1" colspan="1">T. spiralis</th>
<th align="center" valign="middle" rowspan="1" colspan="1">A. suum</th>
<th align="center" valign="middle" rowspan="1" colspan="1">B. malayi</th>
<th align="center" valign="middle" rowspan="1" colspan="1">W. bancrofti</th>
<th align="center" valign="middle" rowspan="1" colspan="1">L. loa</th>
<th align="center" valign="middle" rowspan="1" colspan="1">wBm</th>
<th align="center" valign="middle" rowspan="1" colspan="1">wMel</th>
<th align="center" valign="middle" rowspan="1" colspan="1">wPip</th>
<th align="center" valign="middle" rowspan="1" colspan="1">wWb</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Heme</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">
<xref ref-type="table-fn" rid="TFN2">a</xref>
</td>
<td align="center" rowspan="1" colspan="1">
<xref ref-type="table-fn" rid="TFN2">a</xref>
</td>
<td align="center" rowspan="1" colspan="1">
<xref ref-type="table-fn" rid="TFN2">a</xref>
</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Riboflavin</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">FAD</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+/–</td>
<td align="center" rowspan="1" colspan="1">+/–</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+/–</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Glutathione</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Purines</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">+/–</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Pyrimidines</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+/–</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+/–</td>
<td align="center" rowspan="1" colspan="1">+/–</td>
<td align="center" rowspan="1" colspan="1">+/–</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
<td align="center" rowspan="1" colspan="1">+</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TFN2">
<label>a</label>
<p id="P50">all filarial worms encode a ferrochelatase, the last enzyme in heme synthesis (
<xref ref-type="supplementary-material" rid="SD1">Supplementary Note</xref>
).</p>
</fn>
</table-wrap-foot>
</table-wrap>
<boxed-text id="BX1" position="float" orientation="portrait">
<p id="P51">Editorial Summary: Thomas Nutman and colleagues report the draft genome of the filarial pathogen Loa loa, the African eyeworm. They also report coverage of two other filarial pathogens, Wuchereria bancrofti and Onchocerca volvulus. Unlike most filariae, Loa loa lacks an obligate intracellular Wolbachia endosymbiont, and comparative genomic analyses suggest that the Loa loa genome does not contain novel metabolic synthesis or transport pathways compared to other filariae.</p>
</boxed-text>
</floats-group>
</pmc>
</record>

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