Volume 12 Supplement 1

Beyond the Genome 2011

Open Access

Deciphering the reproductive protein-protein interaction network in Anopheles gambiae with Drosophila melanogasteras a framework

  • Daniel Achinko1,
  • Paul Mireji2,
  • Flaminia Catteruccia3 and
  • Dan Masig1
Genome Biology201112(Suppl 1):P32

https://doi.org/10.1186/gb-2011-12-s1-p32

Published: 19 September 2011

Background

Protein-protein interactions (PPIs) are the most fundamental biological processes at the molecular level. The experimental methods for testing PPIs are time-consuming and are limited by analogs for many reactions. As a result, a computational model is necessary to predict PPIs and to explore the consequences of signal alterations in biological pathways. Reproductive control of the vector Anopheles gambiae using transgenic techniques poses a serious challenge. To meet this challenge, it would help to define the biological network involving the male accessory gland (MAG) proteins responsible for successful formation of the mating plug [1]. This plug forms in the male and is transferred to the female during mating, hence initiating the PPIs in both sexes. As is the case in Drosophila melanogaster, a close relative of A. gambiae, some MAG proteins responsible for the formation of the mating plug have been shown to alter the post-mating behavior of females.

Methods and results

The STRING database for known PPIs was used to identify orthologs of A. gambiae proteins in Drosophila (Table 1). Twenty-seven proteins are known to form the mating plug in A. gambiae, and 16 others were obtained as strings in the STRING database. Chromosome synteny comparisons for proteins with more than 50% identity between species were carried out using the Artemis Comparison Tool (ACT version 9.0), and this showed 24.39% matches (M), 12.20% mismatches (MM) and 63.41% unmatched (NM). The network built in Cytoscape (version 2.8.0) with the UniProt IDs for these Drosophila orthologs showed 14 complexes, with 4 of them being for Drosophila. The network showed 555 nodes and 2,344 edges. The top 50 identified hubs in the network showed a range of 3 to 30 interactions. The expression values for these proteins in FlyAtlas showed that they are upregulated in the reproductive tissues of both sexes. To understand the processes involved in plug formation, the Reactome database was used, and the hub proteins were identified in 49 of the 2,021 known processes in Drosophila. Twelve proteins were involved in the following processes: metabolism of proteins (8.8e–13), gene expression (2.0e–06), 3’-UTR-mediated translational regulation (7.7e–08), regulation of β-cell development (1.3e–06), diabetes pathways (6.8e–06), signal recognition (preprolactin) (5.0e–07) and membrane trafficking (1.3e–03). Of the top 50 proteins, 92% had orthologs in A. gambiae, with one identified in the mating plug and four others identified as strings to AGAP009584, which is found in the mating plug. Acp29AB was identified in the network and is known to induce post-mating responses in Drosophila, confirming that the network is reproductive and giving an insight into the possible pathways involved. The CG9083 (Q8SX59) protein was ranked first among the hub proteins but has no ortholog in A. gambiae. Interestingly, it has the same protein properties as the Plugin protein (AGAP009368) in A. gambiae, suggesting that Plugin may be the main protein in the PPI reproductive network in A. gambiae. The Whelan and Goldman (WAG) maximum likelihood tree evaluations of the plug proteins in A. gambiae and their orthologs in Drosophila showed that these proteins are involved in similar biological processes in both species, but the A. gambiae protein evaluation provided a better explanation for the expected process as it clustered in both pre-mated and post-mated PPIs.
Table 1

Orthologs of Anopheles gambiae proteins in Drosophila identified using the STRING database

A. gambiae ID (plug proteins)

STRING

Chromosome

Sex

Ortholog in Drosophila

UniProt ID

Chromosome

STRING score

Chromosome synteny

AGAP009099

 

3R

Male

CG7356

Q9VLU2

2L

108

MM

     

Q8IPH0

2L

108

MM

AGAP009368

 

3R

Male

CG15005

Q9VZG4

3L

40

NM

AGAP009370

 

3R

Male

     

AGAP012830

 

Unknown

Male

  

Unknown

  

AGAP008276

 

2R

Male

CG12350

Q7JPN9

3R

139

NM

AGAP008277

 

2R

Male

CG12350

Q7JPN9

 

137

MM

AGAP013150 (AGAP004671)

  

Male

CG4738

Q9VKJ3

 

362

NM

AGAP005791

 

2L

Male

CG32834

Q9WIW6

2R

74.7

NM

     

D3DMG3

   

AGAP007041

 

2L

Male

CG6676

Q95SM8

2R

172

NM

AGAP006418

 

2L

Male

CG32679

Q8IRL3

X

166

NM

     

D9PTU6

   

AGAP009673

 

3R

Male

CG5976

Q7KTY3

3L

317

MM

     

Q0GT94

   

AGAP003083

 

2R

Male

CG6113

Q9VKT9

2L

180

NM

AGAP001649

 

2R

Male

CG31414

Q8IMY3

3R

537

M

    

CG3647

Q4V4A3

   
     

Q4V4J1

   
 

AGAP0012412

3L

 

CG6437

Q9W297

2R

583

NM

 

AGAP002055

2R

 

CG3132

Q9VGE7

3R

642

NM

AGAP009584

 

3R

Both

CG31884

Q9V429

2L

134

NM

 

AGAP000565

X

 

CG2151

P91938

X

687

M

    

CG11401

Q9VNT5

3L

687

 
 

AGAP011107

3L

 

CG6852

B7Z076

3L

144

NM

     

Q9VVT6

3L

144

 
 

AGAP010517

3L

 

SOD1

B8YNX4

3L

302

NM

 

AGAP007201

2L

 

TRX-2

Q6HI1

2L

169

NM

 

AGAP007827

3R

 

CG17654

P15007

2L

736

M

 

AGAP009623

3R

 

CG8893

P07487

X

544

M

 

AGAP007120

2L

 

CG2210

P08879

3R

292

NM

 

AGAP006818

2L

 

CG8975

P48592

2R

588

NM

    

CG17797

O46197

2L

  
 

AGAP010198

3R

 

CG5371

P48591

2L

1311

M

 

AGAP001325

2R

 

CG32920

Q960M4

3R

238

NM

    

CG7217

Q6XHE3

3R

  

AGAP012407

 

3L

Both

CG6988

P54399

3L

642

M

 

AGAP007393

2L

 

CG8983

Q3YMU0

2R

696

NM

 

AGAP002816

2R

 

CG1333

Q9V3A6

3L

582

M

AGAP011630

 

3L

Female

CG33998

Q6IG52

2R

66

NM

     

B3DN29

2R

66

 

AGAP004533

 

2R

Both

CG10992

Q9VY87

X

464

M

AGAP005194

 

2L

Female

CG5255

Q9VEM5

3R

154

NM

AGAP005195

 

2L

Female

CG4053

Q9VEM7

3R

136

NM

     

Q9VIT3

2L

  
     

Q8IGA0

2L

  

AGAP006904

 

2L

Female

CG4859

Q9W122

2R

762

M

    

CG4859

Q8MLN6

2R

  
 

AGAP003319

2R

 

CG6281

Q9VH14

3R

148

MM

AGAP007347

 

2L

Female

CG7798

A1ZAB8

2R

131

NM

AGAP003139

 

2R

Both

CG18525

Q9VFC2

3R

293

NM

    

CG18525

Q9VFC2

3R

  

AGAP006964

 

2L

Female

CG32147

Q8SZB7

3L

155

NM

 

AGAP009172

3R

 

CG5355

Q9VKW5

2L

980

M

AGAP006420

 

2L

Both

CG32679

Q8IRL3

X

137

NM

AGAP009212

 

3R

Both

CG7219

A4V9T5

2L

206

NM

NOVEL ACP1 (from female)

 

3R: b/w 9370 & 9371

Male

     

NOVEL ZCP7 (AGAP008071)

 

3R: b/w 5051000 & 5067900

Male

CG8564

Q9VS63

3L

164

NM

This table shows the 27 proteins known to be in the mating plug of A. gambiae[1], derived predominantly from the male. The 16 strings predicted as orthologs in Drosophila, using the STRING database, have varying scores. Scores above 60 can be trusted following their alignments. Plugin, which has the lowest score, has no good ortholog in Drosophila. Most of the proteins are encoded on chromosome arms 2L and 3R in both species. The chromosome synteny comparisons using ACT showed 24.39% matches (M), 12.20% mismatches (MM) and 63.41% unmatched (NM). The presence of gaps between the alignments resulted in the observed MM and NM. The nucleotide sequences at the chromosomal locations where the proteins NOVEL ACP1 and NOVEL ZCP7 are encoded were used to identify similar proteins and their orthologs.

Conclusions

The identification of A. gambiae proteins in this network creates more targets for functional analysis and reproductive control of the malaria vector.

Authors’ Affiliations

(1)
Molecular Biology and Biotechnology Department, International Center of Insect Physiology and Ecology (icipe)
(2)
Biochemistry and Molecular Biology Department, Egerton University
(3)
Division of Cell and Molecular Biology, Imperial College London

References

  1. Rogers DW, Baldini F, Battaglia F, Panico M, Dell A, Morris HR, Catteruccia F: Transglutaminase-mediated semen coagulation controls sperm storage in the malaria mosquito. PLoS Biol. 2009, 7: e1000272-10.1371/journal.pbio.1000272.PubMedPubMed CentralView ArticleGoogle Scholar

Copyright

© Achinko et al; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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