Abstract
The AMPK protein kinase forms the heart of a complex network controlling the metabolic activities in a eukaryotic cell. Unraveling the steps by which this pathway evolved from its primordial roots in the last eukaryotic common ancestor to its present status in contemporary species has the potential to shed light on the evolution of eukaryotes. A homolog search for the proteins interacting in this pathway is considerably straightforward. However, interpreting the results, when reconstructing the evolutionary history of the pathway over larger evolutionary distances, bears a number of pitfalls. With this in mind, we present a protocol to trace a metabolic pathway across contemporary species and backward in evolutionary time. Alongside the individual analysis steps, we provide guidelines for data interpretation generalizing beyond the analysis of AMPK.
Key words
- AMPK evolution
- Targeted ortholog search
- Feature architecture
- Functional equivalence
- Phylogenetic profiles
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References
Wetterstrand KA (2016) DNA sequencing costs: data from the NHGRI large-scale genome sequencing program. www.genome.gov/sequencingcostsdata. Accessed 4 Sept. 2016
Vitulo N, Vezzi A, Romualdi C et al (2007) A global gene evolution analysis on Vibrionaceae family using phylogenetic profile. BMC Bioinformatics 8(Suppl 1):S23. https://doi.org/10.1186/1471-2105-8-S1-S23
Sun J, Xu J, Liu Z et al (2005) Refined phylogenetic profiles method for predicting protein-protein interactions. Bioinformatics 21:3409–3415. https://doi.org/10.1093/bioinformatics/bti532
Pellegrini M, Marcotte EM, Thompson MJ et al (1999) Assigning protein functions by comparative genome analysis: protein phylogenetic profiles. Proc Natl Acad Sci U S A 96:4285–4288. https://doi.org/10.1073/pnas.96.8.4285
Jensen RA (2001) Orthologs and paralogs - we need to get it right. Genome Biol 2(8):interactions1002.1–interactions1002.3. https://doi.org/10.1186/gb-2001-2-8-interactions1002
Baldauf SL (2003) Phylogeny for the faint of heart: a tutorial. Trends Genet 19:345–351. https://doi.org/10.1016/S0168-9525(03)00112-4
Koonin EV (2005) Orthologs, paralogs, and evolutionary genomics. Annu Rev Genet 39:309–338. https://doi.org/10.1146/annurev.genet.39.073003.114725
Dolinski K, Botstein D (2007) Orthology and functional conservation in eukaryotes. Annu Rev Genet 41:465–507. https://doi.org/10.1146/annurev.genet.40.110405.090439
Studer RA, Robinson-Rechavi M (2009) How confident can we be that orthologs are similar, but paralogs differ? Trends Genet 25:210–216. https://doi.org/10.1016/j.tig.2009.03.004
Nehrt NL, Clark WT, Radivojac P, Hahn MW (2011) Testing the ortholog conjecture with comparative functional genomic data from mammals. PLoS Comput Biol 7(6):e1002073. https://doi.org/10.1371/journal.pcbi.1002073
Gabaldón T, Koonin EV (2013) Functional and evolutionary implications of gene orthology. Nat Rev Genet 14:360–366. https://doi.org/10.1038/nrg3456
Roustan V, Jain A, Teige M et al (2016) An evolutionary perspective of AMPK-TOR signaling in the three domains of life. J Exp Bot 67:3897–3907. https://doi.org/10.1093/jxb/erw211
Kanehisa M, Goto S (2000) KEGG: kyoto encyclopaedia of genes and genomes. Nucleic Acids Res 28:27–30. https://doi.org/10.1093/nar/28.1.27
Nordberg H, Cantor M, Dusheyko S et al (2014) The genome portal of the department of energy joint genome institute: 2014 updates. Nucleic Acids Res 42(Database issue):D26–D31. https://doi.org/10.1093/nar/gkt1069
Bateman A, Martin MJ, O’Donovan C et al (2015) UniProt: a hub for protein information. Nucleic Acids Res 43:D204–D212. https://doi.org/10.1093/nar/gku989
Herrero J, Muffato M, Beal K et al (2016) Ensembl comparative genomics resources. Database 2016:baw053. https://doi.org/10.1093/database/bav096
Sonnhammer ELL, Gabaldon T, Sousa Da Silva AW et al (2014) Big data and other challenges in the quest for orthologs. Bioinformatics 30:2993–2998. https://doi.org/10.1093/bioinformatics/btu492
Kelder T, Van Iersel MP, Hanspers K et al (2012) WikiPathways: building research communities on biological pathways. Nucleic Acids Res 40(Database issue):D1301–D1307. https://doi.org/10.1093/nar/gkr1074
Fabregat A, Sidiropoulos K, Garapati P et al (2016) The reactome pathway knowledgebase. Nucleic Acids Res 44:D481–D487. https://doi.org/10.1093/nar/gkv1351
Cerami EG, Gross BE, Demir E et al (2011) Pathway commons, a web resource for biological pathway data. Nucleic Acids Res 39(Database):D685–D690. https://doi.org/10.1093/nar/gkq1039
Sonnhammer ELL, Östlund G (2015) InParanoid 8: orthology analysis between 273 proteomes, mostly eukaryotic. Nucleic Acids Res 43:D234–D239. https://doi.org/10.1093/nar/gku1203
Altenhoff AM, Boeckmann B, Capella-Gutierrez S et al (2016) Standardized benchmarking in the quest for orthologs. Nat Methods 13:425–430. https://doi.org/10.1038/nmeth.3830
Altenhoff AM, Šunca N, Glover N et al (2015) The OMA orthology database in 2015: function predictions, better plant support, synteny view and other improvements. Nucleic Acids Res 43:D240–D249. https://doi.org/10.1093/nar/gku1158
Zdobnov EM, Tegenfeldt F, Kuznetsov D et al (2016) OrthoDB v9.1: cataloging evolutionary and functional annotations for animal, fungal, plant, archaeal, bacterial and viral orthologs. Nucleic Acids Res 45(D1):D744–D749. https://doi.org/10.1093/nar/gkw1119
Ebersberger I, Strauss S, von Haeseler A (2009) HaMStR: profile hidden markov model based search for orthologs in ESTs. BMC Evol Biol 9:157. https://doi.org/10.1186/1471-2148-9-157
Ebersberger I, Simm S, Leisegang MS et al (2014) The evolution of the ribosome biogenesis pathway from a yeast perspective. Nucleic Acids Res 42:1509–1523. https://doi.org/10.1093/nar/gkt1137
Jones P, Binns D, Chang HY et al (2014) InterProScan 5: genome-scale protein function classification. Bioinformatics 30:1236–1240. https://doi.org/10.1093/bioinformatics/btu031
Finn RD, Mistry J, Tate J et al (2010) The Pfam protein families database. Nucleic Acids Res 38:D211–D222. https://doi.org/10.1093/nar/gkm960
Koestler T, von Haeseler A, Ebersberger I (2010) FACT: functional annotation transfer between proteins with similar feature architectures. BMC Bioinformatics 11:417. https://doi.org/10.1186/1471-2105-11-417
Moore AD, Heldy A, Terrapon N et al (2014) DoMosaics: software for domain arrangement visualization and domain-centric analysis of proteins. Bioinformatics 30:282–283. https://doi.org/10.1093/bioinformatics/btt640
Finn RD, Clements J, Arndt W et al (2015) HMMER web server: 2015 update. Nucleic Acids Res 43:W30–W38. https://doi.org/10.1093/nar/gkv397
Edgar RC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797. https://doi.org/10.1093/nar/gkh340
Katoh K, Standley DM (2013) MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol Biol Evol 30:772–780. https://doi.org/10.1093/molbev/mst010
Darriba D, Taboada GL, Doallo R, Posada D (2011) ProtTest-HPC: fast selection of best-fit models of protein evolution. In: Lect. Notes Comput. Sci. (including Subser. Lect. Notes Artif. Intell. Lect. Notes Bioinformatics). pp 177–184
Stamatakis A (2014) RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30:1312–1313. https://doi.org/10.1093/bioinformatics/btu033
Rambaut A (2009) FigTree v1.3.1. 2006–2009. Program package available at http://tree.bio.ed.ac. Accessed 29 Nov. 2012
Pipinellis A (2015) GitHub essentials. Packt Publishing Ltd., Birmingham
Glez-Peña D, Gómez-Blanco D, Reboiro-Jato M et al (2010) ALTER: program-oriented conversion of DNA and protein alignments. Nucleic Acids Res 38(Web Server issue):W14–W18. https://doi.org/10.1093/nar/gkq321
Larkin MA, Blackshields G, Brown NP et al (2007) ClustalW and ClustalX version 2.0. Bioinformatics 23:2947–2948. https://doi.org/10.1093/bioinformatics/btm404
Penn O, Privman E, Ashkenazy H et al (2010) GUIDANCE: a web server for assessing alignment confidence scores. Nucleic Acids Res 38(Web Server issue):W23–W28. https://doi.org/10.1093/nar/gkq443
Chang JM, Di Tommaso P, Notredame C (2014) TCS: a new multiple sequence alignment reliability measure to estimate alignment accuracy and improve phylogenetic tree reconstruction. Mol Biol Evol 31:1625–1637. https://doi.org/10.1093/molbev/msu117
Le SQ, Gascuel O (2008) An improved general amino acid replacement matrix. Mol Biol Evol 25:1307–1320. https://doi.org/10.1093/molbev/msn067
Goldman N, Anderson JP, Rodrigo a G (2000) Likelihood-based tests of topologies in phylogenetics. Syst Biol 49:652–670. https://doi.org/10.1080/106351500750049752
Shimodaira H, Hasegawa M (1999) Multiple comparisons of log-likelihoods with applications to phylogenetic inference. Mol Biol Evol 16:1114–1116. https://doi.org/10.1177/0148607109348061
Acknowledgment
This work was supported by the Marie Curie ITN project CALIPSO (GA ITN-2013 607 607), and by the Deutsche Forschungsgesellschaft (EB 285/2-1).
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Jain, A., Roustan, V., Weckwerth, W., Ebersberger, I. (2018). Studying AMPK in an Evolutionary Context. In: Neumann, D., Viollet, B. (eds) AMPK. Methods in Molecular Biology, vol 1732. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7598-3_8
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DOI: https://doi.org/10.1007/978-1-4939-7598-3_8
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