Bacterial Protein Interaction Networks: Connectivity is Ruled by Gene Conservation, Essentiality and Function

Author(s): Maddalena Dilucca*, Giulio Cimini, Andrea Giansanti

Journal Name: Current Genomics

Volume 22 , Issue 2 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Protein-protein interaction (PPI) networks are the backbone of all processes in living cells. In this work, we relate conservation, essentiality and functional repertoire of a gene to the connectivity k (i.e. the number of interactions, links) of the corresponding protein in the PPI network.

Methods: On a set of 42 bacterial genomes of different sizes, and with reasonably separated evolutionary trajectories, we investigate three issues: i) whether the distribution of connectivities changes between PPI subnetworks of essential and nonessential genes; ii) how gene conservation, measured both by the evolutionary retention index (ERI) and by evolutionary pressures, is related to the connectivity of the corresponding protein; iii) how PPI connectivities are modulated by evolutionary and functional relationships, as represented by the Clusters of Orthologous Genes (COGs).

Results: We show that conservation, essentiality and functional specialisation of genes constrain the connectivity of the corresponding proteins in bacterial PPI networks. In particular, we isolated a core of highly connected proteins (connectivities k≥40), which is ubiquitous among the species considered here, though mostly visible in the degree distributions of bacteria with small genomes (less than 1000 genes).

Conclusion: The genes that support this highly connected core are conserved, essential and, in most cases, belong to the COG cluster J, related to ribosomal functions and the processing of genetic information.

Keywords: Protein-protein interactions, gene essentiality, evolutionary retention index, clusters of orthologous genes, bacterial genomes, cellular processes.

[1]
Drewes, G.; Bouwmeester, T. Global approaches to protein-protein interactions. Curr. Opin. Cell Biol., 2003, 15(2), 199-205.
[http://dx.doi.org/10.1016/S0955-0674(03)00005-X ] [PMID: 12648676]
[2]
Golemis, E.; Adams, P.D. Protein-protein Interactions: A Molecular Cloning Manual.; Cold Spring Harbor Laboratory Press; , 2005.
[3]
von Mering, C.; Krause, R.; Snel, B.; Cornell, M.; Oliver, S.G.; Fields, S.; Bork, P. Comparative assessment of large-scale data sets of protein-protein interactions. Nature, 2002, 417(6887), 399-403.
[http://dx.doi.org/10.1038/nature750 ] [PMID: 12000970]
[4]
Tong, A.H.; Drees, B.; Nardelli, G.; Bader, G.D.; Brannetti, B.; Castagnoli, L.; Evangelista, M.; Ferracuti, S.; Nelson, B.; Paoluzi, S.; Quondam, M.; Zucconi, A.; Hogue, C.W.V.; Fields, S.; Boone, C.; Cesareni, G. A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules. Science, 2002, 295(5553), 321-324.
[http://dx.doi.org/10.1126/science.1064987 ] [PMID: 11743162]
[5]
Shatsky, M.; Allen, S.; Gold, B.L.; Liu, N.L.; Juba, T.R.; Reveco, S.A.; Elias, D.A.; Prathapam, R.; He, J.; Yang, W.; Szakal, E.D.; Liu, H.; Singer, M.E.; Geller, J.T.; Lam, B.R.; Saini, A.; Trotter, V.V.; Hall, S.C.; Fisher, S.J.; Brenner, S.E.; Chhabra, S.R.; Hazen, T.C.; Wall, J.D.; Witkowska, H.E.; Biggin, M.D.; Chandonia, J.M.; Butland, G. Bacterial interactomes: Interacting protein partners share similar function and are validated in independent assays more frequently than previously reported. Mol. Cell. Proteomics, 2016, 15(5), 1539-1555.
[http://dx.doi.org/10.1074/mcp.M115.054692 ] [PMID: 26873250]
[6]
Harry, C.; Wimble, J.C.; Shary, S.; Wuchty, S.; Uetz, P. Bacterial protein meta-interactomes predict cross-species interactions and protein function. BMC Bioinformatics, 2017, 18(1), 171.
[http://dx.doi.org/10.1186/s12859-017-1585-0 ] [PMID: 28298180]
[7]
Dilucca, M.; Cimini, G.; Semmoloni, A.; Deiana, A.; Giansanti, A. Codon bias patterns of E. coli’s interacting proteins. PLoS One, 2015, 10(11), e0142127.
[http://dx.doi.org/10.1371/journal.pone.0142127 ] [PMID: 26566157]
[8]
Dilucca, M.; Cimini, G.; Giansanti, A. Essentiality, conservation, evolutionary pressure and codon bias in bacterial genomes. Gene, 2018, 663, 178-188.
[http://dx.doi.org/10.1016/j.gene.2018.04.017 ] [PMID: 29678658]
[9]
Gerdes, S.Y.; Scholle, M.D.; Campbell, J.W.; Balázsi, G.; Ravasz, E.; Daugherty, M.D.; Somera, A.L.; Kyrpides, N.C.; Anderson, I.; Gelfand, M.S.; Bhattacharya, A.; Kapatral, V.; D’Souza, M.; Baev, M.V.; Grechkin, Y.; Mseeh, F.; Fonstein, M.Y.; Overbeek, R.; Barabási, A.L.; Oltvai, Z.N.; Osterman, A.L. Experimental determination and system level analysis of essential genes in Escherichia coli MG1655. J. Bacteriol., 2003, 185(19), 5673-5684.
[http://dx.doi.org/10.1128/JB.185.19.5673-5684.2003 ] [PMID: 13129938]
[10]
Fang, G.; Rocha, E.; Danchin, A. How essential are nonessential genes? Mol. Biol. Evol., 2005, 22(11), 2147-2156.
[http://dx.doi.org/10.1093/molbev/msi211 ] [PMID: 16014871]
[11]
Peng, C.; Gao, F. Protein localization analysis of essential genes in prokaryotes. Sci. Rep., 2014, 4, 6001.
[http://dx.doi.org/10.1038/srep06001 ] [PMID: 25105358]
[12]
Lin, Y.; Gao, F.; Zhang, C.-T. Functionality of essential genes drives gene strand-bias in bacterial genomes. Biochem. Biophys. Res. Commun., 2010, 396(2), 472-476.
[http://dx.doi.org/10.1016/j.bbrc.2010.04.119 ] [PMID: 20417622]
[13]
Hurst, L.D.; Smith, N.G. Do essential genes evolve slowly? Curr. Biol., 1999, 9(14), 747-750.
[http://dx.doi.org/10.1016/S0960-9822(99)80334-0 ] [PMID: 10421576]
[14]
Jordan, I.K.; Rogozin, I.B.; Wolf, Y.I.; Koonin, E.V. Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res., 2002, 12(6), 962-968.
[http://dx.doi.org/10.1101/gr.87702 ] [PMID: 12045149]
[15]
Luo, H.; Gao, F.; Lin, Y. Evolutionary conservation analysis between the essential and nonessential genes in bacterial genomes. Sci. Rep., 2015, 5, 13210.
[http://dx.doi.org/10.1038/srep13210 ] [PMID: 26272053]
[16]
Ish-Am, O.; Kristensen, D.M.; Ruppin, E.; David, M.K.; Ruppin, E. Evolutionary conservation of bacterial essential metabolic genes across all bacterial culture media. PLoS One, 2015, 10(4), e0123785.
[http://dx.doi.org/10.1371/journal.pone.0123785 ] [PMID: 25894004]
[17]
Alvarez-Ponce, D.; Sabater-Muñoz, B.; Toft, C.; Ruiz-González, M.X.; Fares, M.A.; Sabater-Munoz, B.; Toft, C.; Ruiz-Gonz’alez, M.X.; Fares, M.A. Essentiality is a strong determinant of protein rates of evolution during mutation accumulation experiments in Escherichia coli. Genome Biol. Evol., 2016, 8(9), 2914-2927.
[http://dx.doi.org/10.1093/gbe/evw205 ] [PMID: 27566759]
[18]
Bergmiller, T.; Ackermann, M.; Silander, O.K. Patterns of evolutionary conservation of essential genes correlate with their compensability. PLoS Genet., 2012, 8(6), e1002803.
[http://dx.doi.org/10.1371/journal.pgen.1002803 ] [PMID: 22761596]
[19]
Hurst, L.D. The Ka/Ks ratio: diagnosing the form of sequence evolution. Trends Genet., 2002, 18(9), 486-487.
[http://dx.doi.org/10.1016/S0168-9525(02)02722-1 ] [PMID: 12175810]
[20]
Benson, D.A.; Cavanaugh, M.; Clark, K.; Karsch-Mizrachi, I.; Lipman, D.J.; Ostell, J.; Sayers, E.W. Genbank Nucleic Acids Res., 2013, 41(D1), D36-D42.
[21]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368.
[http://dx.doi.org/10.1093/nar/gkw937 ] [PMID: 27924014]
[22]
Chien, C.T.; Bartel, P.L.; Sternglanz, R.; Fields, S. The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. Proc. Natl. Acad. Sci. USA, 1991, 88(21), 9578-9582.
[http://dx.doi.org/10.1073/pnas.88.21.9578 ] [PMID: 1946372]
[23]
Phizicky, E.M.; Fields, S. Protein-protein interactions: methods for detection and analysis. Microbiol. Rev., 1995, 59(1), 94-123.
[http://dx.doi.org/10.1128/MR.59.1.94-123.1995 ] [PMID: 7708014]
[24]
Puig, O.; Caspary, F.; Rigaut, G.; Rutz, B.; Bouveret, E.; Bragado-Nilsson, E.; Wilm, M.; Séraphin, B. The tandem affinity purification (TAP) method: a general procedure of protein complex purification. Methods, 2001, 24(3), 218-229.
[http://dx.doi.org/10.1006/meth.2001.1183 ] [PMID: 11403571]
[25]
Kanehisa, M.; Goto, S. KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res., 2000, 28(1), 27-30.
[http://dx.doi.org/10.1093/nar/28.1.27 ] [PMID: 10592173]
[26]
Nei, M.; Gojobori, T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol. Biol. Evol., 1986, 3(5), 418-426.
[PMID: 3444411]
[27]
Zhang, R.; Lin, Y. DEG 5.0, a database of essential genes in both prokaryotes and eukaryotes. Nucleic Acids Res., 2009, 37(Database issue)(Suppl. 1), D455-D458.
[http://dx.doi.org/10.1093/nar/gkn858 ] [PMID: 18974178]
[28]
Luo, H.; Lin, Y.; Gao, F.; Zhang, C-T.; Zhang, R. DEG 10, an update of the database of essential genes that includes both protein- coding genes and noncoding genomic elements. Nucleic Acids Res., 2014, 42(Database issue), D574-D580.
[http://dx.doi.org/10.1093/nar/gkt1131 ] [PMID: 24243843]
[29]
Wright, F. The ‘effective number of codons’ used in a gene. Gene, 1990, 87(1), 23-29.
[http://dx.doi.org/10.1016/0378-1119(90)90491-9 ] [PMID: 2110097]
[30]
Roman, L.; Tatusov, D.A.; Natale, I.V. Garkavtsev, T.A. Tatusova, U.T. Shankavaram, Rao, B.S.; Kiryutin, B.; Galperin, M.Y.; Fedorova, N.D.; Koonin, E.V. The cog database: New developments in phylogenetic classifi- cation of proteins from complete genomes. Nucleic Acids Res., 2001, 29(1), 22.
[PMID: 11125040]
[31]
Michael, Y.; Makarova, K.S.; Wolf, Y.I.; Koonin, E.V. Expanded microbial genome coverage and improved protein family annotation in the cog database. Nucleic Acids Res., 2015, 43(D1), D261.
[http://dx.doi.org/10.1093/nar/gku1223]
[32]
Butland, G.; Peregrín-Alvarez, J.M.; Li, J.; Yang, W.; Yang, X.; Canadien, V.; Starostine, A.; Richards, D.; Beattie, B.; Krogan, N.; Davey, M.; Parkinson, J.; Greenblatt, J.; Emili, A. Interaction network containing conserved and essential protein complexes in Escherichia coli. Nature, 2005, 433(7025), 531-537.
[http://dx.doi.org/10.1038/nature03239 ] [PMID: 15690043]
[33]
Jin, Y.; Turaev, D.; Weinmaier, T.; Rattei, T.; Makse, H.A. The evolutionary dynamics of protein-protein interaction networks inferred from the reconstruction of ancient networks. PLoS One, 2013, 8(3), e58134.
[http://dx.doi.org/10.1371/journal.pone.0058134 ] [PMID: 23526967]
[34]
Rajagopala, S.V.; Sikorski, P.; Kumar, A.; Mosca, R.; Vlasblom, J.; Arnold, R.; Franca-Koh, J.; Pakala, S.B.; Phanse, S.; Ceol, A.; H¨auser, R.; Siszler, G.; Wuchty, S.; Emili, A.; Babu, Mohan.; Aloy, P.; Pieper, R.; Uetz, P. The binary protein-protein inter- action landscape of Escherichia coli. Nat. Biotechnol., 2014, 32, 285-290.
[35]
Hahn, M.W.; Kern, A.D. Comparative genomics of centrality and essentiality in three eukaryotic protein-interaction networks. Mol. Biol. Evol., 2005, 22(4), 803-806.
[http://dx.doi.org/10.1093/molbev/msi072 ] [PMID: 15616139]
[36]
Karimpour-Fard, A.; Leach, S.M.; Hunter, L.E.; Gill, R.T. The topology of the bacterial co-conserved protein network and its implications for predicting protein function. BMC Genomics, 2008, 9(1), 313.
[http://dx.doi.org/10.1186/1471-2164-9-313 ] [PMID: 18590549]
[37]
Wuchty, S.; Uetz, P. Protein-protein interaction networks of E. coli and S. cerevisiae are similar. Sci. Rep., 2014, 4, 7187.
[http://dx.doi.org/10.1038/srep07187 ] [PMID: 25431098]
[38]
Annibale, A.; Coolen, A.C.C.; Planell-Morell, N. 2015.
[39]
Bader, G.D.; Hogue, C.W. An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinformatics, 2003, 4(2), 2.
[http://dx.doi.org/10.1186/1471-2105-4-2 ] [PMID: 12525261]
[40]
Balaji, S. Novak, Antal F.; Flannick, Jason A.; Batzoglou, Serafim.; McAdams, Harley H. Integrated Protein Interaction Networks for 11 Microbes.; Springer Berlin Heidelberg; , 2006, pp. pp. 1-14.
[41]
Rao, V.S.; Srinivas, K.; Sujini, G.N.; Kumar, G.N. Protein-protein interaction detection: methods and analysis. Int. J. Proteomics, 2014, 2014(147648), 147648.
[PMID: 24693427]
[42]
Jeong, H.; Mason, S.P.; Barabási, A-L.; Oltvai, Z.N. Lethality and centrality in protein networks. Nature, 2001, 411(6833), 41-42.
[http://dx.doi.org/10.1038/35075138 ] [PMID: 11333967]
[43]
George, E. Fox. Origin and evolution of the ribosome. Cold Spring Harb. Perspect. Biol., 2010, 2(9), a003483.
[44]
Hwang, Y.-C.; Lin, C.-C.; Chang, J.-Y.; Juan, H.-F.; Huang, H.-C. Predicting essential genes based on network and sequence analysis. Mol. Biosyst., 2009, 5, 1672-1678.
[45]
Wei, W.; Ning, L.-W.; Ye, Y.-N.; Guo, F.-B. Geptop: a gene essentiality prediction tool for sequenced bacterial genomes based on orthology and phylogeny. PLoS One, 2013, 8(8), e72343.
[http://dx.doi.org/10.1371/journal.pone.0072343 ] [PMID: 23977285]
[46]
Bardini, R.; Di Carlo, S.; Politano, G.; Benso, A. Modeling antibiotic resistance in the microbiota using multi-level petri nets. BMC Syst. Biol., 2018, 12(6), 108.
[http://dx.doi.org/10.1186/s12918-018-0627-1]
[47]
Terradot, L.; Noirot-Gros, M.-F. Bacterial protein interaction networks: puzzle stones from solved complex structures add to a clearer picture. Integr. Biol., 2011, 3, 645-652.
[http://dx.doi.org/10.1039/c0ib00023j]
[48]
Zoraghi, R.; Reiner, N.E. Protein interaction networks as starting points to identify novel antimicrobial drug targets. Curr. Opin. Microbiol., 2013, 16(5), 566-572.
[http://dx.doi.org/10.1016/j.mib.2013.07.010 ] [PMID: 23938265]
[49]
Sevimoglu, T.; Arga, K.Y. The role of protein interaction networks in systems biomedicine. Comput. Struct. Biotechnol. J., 2014, 11(18), 22-27.
[http://dx.doi.org/10.1016/j.csbj.2014.08.008 ] [PMID: 25379140]
[50]
Boccaletti, S.; Bianconi, G.; Criado, R.; Del Genio, C.I.; Gómez- Gardeñes, J.; Romance, M.; Sendiña-Nadal, I.; Wang, Z.; Zanin, M. The structure and dynamics of multilayer networks. Phys. Rep., 2014, 544(1), 1-122.
[http://dx.doi.org/10.1016/j.physrep.2014.07.001 ] [PMID: 32834429]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 22
ISSUE: 2
Year: 2021
Published on: 18 February, 2021
Page: [111 - 121]
Pages: 11
DOI: 10.2174/1389202922666210219110831
Price: $65

Article Metrics

PDF: 162
HTML: 1