Functional Divergence and Evolutionary Turnover in Mammalian Phosphoproteomes
Protein phosphorylation is a key mechanism to regulate protein functions. However, the contribution of this protein modification to species divergence is still largely unknown. Here, we studied the evolution of mammalian phosphoregulation by comparing the human and mouse phosphoproteomes. We found that 84% of the positions that are phosphorylated in one species or the other are conserved at the residue level. Twenty percent of these conserved sites are phosphorylated in both species. This proportion is 2.5 times more than expected by chance alone, suggesting that purifying selection is preserving phosphoregulation. However, we show that the majority of the sites that are conserved at the residue level are differentially phosphorylated between species. These sites likely result from false-negative identifications due to incomplete experimental coverage, false-positive identifications and non-functional sites. In addition, our results suggest that at least 5% of them are likely to be true differentially phosphorylated sites and may thus contribute to the divergence in phosphorylation networks between mouse and humans and this, despite residue conservation between orthologous proteins. We also showed that evolutionary turnover of phosphosites at adjacent positions (in a distance range of up to 40 amino acids) in human or mouse leads to an over estimation of the divergence in phosphoregulation between these two species. These sites tend to be phosphorylated by the same kinases, supporting the hypothesis that they are functionally redundant. Our results support the hypothesis that the evolutionary turnover of phosphorylation sites contributes to the divergence in phosphorylation profiles while preserving phosphoregulation. Overall, our study provides advanced analyses of mammalian phosphoproteomes and a framework for the study of their contribution to phenotypic evolution.
Vyšlo v časopise:
Functional Divergence and Evolutionary Turnover in Mammalian Phosphoproteomes. PLoS Genet 10(1): e32767. doi:10.1371/journal.pgen.1004062
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004062
Souhrn
Protein phosphorylation is a key mechanism to regulate protein functions. However, the contribution of this protein modification to species divergence is still largely unknown. Here, we studied the evolution of mammalian phosphoregulation by comparing the human and mouse phosphoproteomes. We found that 84% of the positions that are phosphorylated in one species or the other are conserved at the residue level. Twenty percent of these conserved sites are phosphorylated in both species. This proportion is 2.5 times more than expected by chance alone, suggesting that purifying selection is preserving phosphoregulation. However, we show that the majority of the sites that are conserved at the residue level are differentially phosphorylated between species. These sites likely result from false-negative identifications due to incomplete experimental coverage, false-positive identifications and non-functional sites. In addition, our results suggest that at least 5% of them are likely to be true differentially phosphorylated sites and may thus contribute to the divergence in phosphorylation networks between mouse and humans and this, despite residue conservation between orthologous proteins. We also showed that evolutionary turnover of phosphosites at adjacent positions (in a distance range of up to 40 amino acids) in human or mouse leads to an over estimation of the divergence in phosphoregulation between these two species. These sites tend to be phosphorylated by the same kinases, supporting the hypothesis that they are functionally redundant. Our results support the hypothesis that the evolutionary turnover of phosphorylation sites contributes to the divergence in phosphorylation profiles while preserving phosphoregulation. Overall, our study provides advanced analyses of mammalian phosphoproteomes and a framework for the study of their contribution to phenotypic evolution.
Zdroje
1. NussinovR, TsaiCJ, XinF, RadivojacP (2012) Allosteric post-translational modification codes. Trends in biochemical sciences 37: 447–455.
2. BeausoleilSA, JedrychowskiM, SchwartzD, EliasJE, VillenJ, et al. (2004) Large-scale characterization of HeLa cell nuclear phosphoproteins. Proceedings of the National Academy of Sciences of the United States of America 101: 12130–12135.
3. ChoudharyC, KumarC, GnadF, NielsenML, RehmanM, et al. (2009) Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 325: 834–840.
4. ZielinskaDF, GnadF, WisniewskiJR, MannM (2010) Precision mapping of an in vivo N-glycoproteome reveals rigid topological and sequence constraints. Cell 141: 897–907.
5. KimW, BennettEJ, HuttlinEL, GuoA, LiJ, et al. (2011) Systematic and quantitative assessment of the ubiquitin-modified proteome. Molecular cell 44: 325–340.
6. HuttlinEL, JedrychowskiMP, EliasJE, GoswamiT, RadR, et al. (2010) A tissue-specific atlas of mouse protein phosphorylation and expression. Cell 143: 1174–1189.
7. OlsenJV, BlagoevB, GnadF, MacekB, KumarC, et al. (2006) Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127: 635–648.
8. VazquezF, RamaswamyS, NakamuraN, SellersWR (2000) Phosphorylation of the PTEN tail regulates protein stability and function. Molecular and cellular biology 20: 5010–5018.
9. SprangSR, AcharyaKR, GoldsmithEJ, StuartDI, VarvillK, et al. (1988) Structural changes in glycogen phosphorylase induced by phosphorylation. Nature 336: 215–221.
10. MadeoF, SchlauerJ, ZischkaH, MeckeD, FrohlichKU (1998) Tyrosine phosphorylation regulates cell cycle-dependent nuclear localization of Cdc48p. Molecular biology of the cell 9: 131–141.
11. KhmelinskiiA, RoostaluJ, RoqueH, AntonyC, SchiebelE (2009) Phosphorylation-Dependent Protein Interactions at the Spindle Midzone Mediate Cell Cycle Regulation of Spindle Elongation. Developmental Cell 17: 244–256.
12. HerbigU, GriffithJW, FanningE (2000) Mutation of cyclin/cdk phosphorylation sites in HsCdc6 disrupts a late step in initiation of DNA replication in human cells. Molecular Biology of the Cell 11: 4117–4130.
13. KimDS, HahnY (2011) Identification of novel phosphorylation modification sites in human proteins that originated after the human-chimpanzee divergence. Bioinformatics 27: 2494–2501.
14. BoulaisJ, TrostM, LandryCR, DieckmannR, LevyED, et al. (2010) Molecular characterization of the evolution of phagosomes. Molecular systems biology 6: 423.
15. MalikR, NiggEA, KornerR (2008) Comparative conservation analysis of the human mitotic phosphoproteome. Bioinformatics 24: 1426–1432.
16. GnadF, RenS, CoxJ, OlsenJV, MacekB, et al. (2007) PHOSIDA (phosphorylation site database): management, structural and evolutionary investigation, and prediction of phosphosites. Genome biology 8: R250.
17. LandryCR, LevyED, MichnickSW (2009) Weak functional constraints on phosphoproteomes. Trends in genetics: TIG 25: 193–197.
18. BoekhorstJ, van BreukelenB, HeckAJr, SnelB (2008) Comparative phosphoproteomics reveals evolutionary and functional conservation of phosphorylation across eukaryotes. Genome biology 9: R144.
19. TanCS, BodenmillerB, PasculescuA, JovanovicM, HengartnerMO, et al. (2009) Comparative analysis reveals conserved protein phosphorylation networks implicated in multiple diseases. Science signaling 2: ra39.
20. LevyE, MichnickS, LandryC (2012) Protein abundance is key to distinguish promiscuous from functional phosphorylation based on evolutionary information. Philosophical transactions of the Royal Society of London Series B, Biological sciences 367: 2594–2606.
21. UbersaxJA, FerrellJEJr (2007) Mechanisms of specificity in protein phosphorylation. Nature reviews Molecular cell biology 8: 530–541.
22. BeltraoP, TrinidadJC, FiedlerD, RoguevA, LimWA, et al. (2009) Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species. PLoS biology 7: e1000134.
23. SkouJC (1965) Enzymatic Basis for Active Transport of Na+ and K+ across Cell Membrane. Physiological Reviews 45: 596–&.
24. BarrRK, BogoyevitchMA (2001) The c-Jun N-terminal protein kinase family of mitogen-activated protein kinases (JNK MAPKs). International Journal of Biochemistry & Cell Biology 33: 1047–1063.
25. SerberZ, FerrellJEJr (2007) Tuning bulk electrostatics to regulate protein function. Cell 128: 441–444.
26. BaAN, MosesAM (2010) Evolution of characterized phosphorylation sites in budding yeast. Molecular biology and evolution 27: 2027–2037.
27. MacekB, GnadF, SoufiB, KumarC, OlsenJV, et al. (2008) Phosphoproteome analysis of E. coli reveals evolutionary conservation of bacterial Ser/Thr/Tyr phosphorylation. Molecular & cellular proteomics: MCP 7: 299–307.
28. FreschiL, CourcellesM, ThibaultP, MichnickSW, LandryCR (2011) Phosphorylation network rewiring by gene duplication. Molecular systems biology 7: 504.
29. MosesAM, LikuME, LiJJ, DurbinR (2007) Regulatory evolution in proteins by turnover and lineage-specific changes of cyclin-dependent kinase consensus sites. Proceedings of the National Academy of Sciences of the United States of America 104: 17713–17718.
30. BellSP, DuttaA (2002) DNA replication in eukaryotic cells. Annual review of biochemistry 71: 333–374.
31. HoltLJ, TuchBB, VillenJ, JohnsonAD, GygiSP, et al. (2009) Global Analysis of Cdk1 Substrate Phosphorylation Sites Provides Insights into Evolution. Science 325: 1682–1686.
32. BeltraoP, AlbaneseV, KennerLR, SwaneyDL, BurlingameA, et al. (2012) Systematic functional prioritization of protein posttranslational modifications. Cell 150: 413–425.
33. GnadF, GunawardenaJ, MannM (2011) PHOSIDA 2011: the posttranslational modification database. Nucleic acids research 39: D253–260.
34. DinkelH, ChicaC, ViaA, GouldCM, JensenLJ, et al. (2011) Phospho.ELM: a database of phosphorylation sites–update 2011. Nucleic acids research 39: D261–267.
35. HornbeckPV, KornhauserJM, TkachevS, ZhangB, SkrzypekE, et al. (2012) PhosphoSitePlus: a comprehensive resource for investigating the structure and function of experimentally determined post-translational modifications in man and mouse. Nucleic acids research 40: D261–270.
36. MinguezP, ParcaL, DiellaF, MendeDR, KumarR, et al. (2012) Deciphering a global network of functionally associated post-translational modifications. Molecular systems biology 8: 599.
37. Keshava PrasadTS, GoelR, KandasamyK, KeerthikumarS, KumarS, et al. (2009) Human Protein Reference Database–2009 update. Nucleic acids research 37: D767–772.
38. IakouchevaLM, RadivojacP, BrownCJ, O'ConnorTR, SikesJG, et al. (2004) The importance of intrinsic disorder for protein phosphorylation. Nucleic acids research 32: 1037–1049.
39. EisenbergE, LevanonEY (2003) Human housekeeping genes are compact. Trends in genetics: TIG 19: 362–365.
40. LiuX, YuX, ZackDJ, ZhuH, QianJ (2008) TiGER: a database for tissue-specific gene expression and regulation. BMC bioinformatics 9: 271.
41. MillerML, JensenLJ, DiellaF, JorgensenC, TintiM, et al. (2008) Linear motif atlas for phosphorylation-dependent signaling. Science signaling 1: ra2.
42. HuttiJE, JarrellET, ChangJD, AbbottDW, StorzP, et al. (2004) A rapid method for determining protein kinase phosphorylation specificity. Nature methods 1: 27–29.
43. GwinnDM, ShackelfordDB, EganDF, MihaylovaMM, MeryA, et al. (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Molecular cell 30: 214–226.
44. BullockAN, DasS, DebreczeniJE, RellosP, FedorovO, et al. (2009) Kinase domain insertions define distinct roles of CLK kinases in SR protein phosphorylation. Structure 17: 352–362.
45. PikeAC, RellosP, NiesenFH, TurnbullA, OliverAW, et al. (2008) Activation segment dimerization: a mechanism for kinase autophosphorylation of non-consensus sites. The EMBO journal 27: 704–714.
46. DavisTL, WalkerJR, Allali-HassaniA, ParkerSA, TurkBE, et al. (2009) Structural recognition of an optimized substrate for the ephrin family of receptor tyrosine kinases. The FEBS journal 276: 4395–4404.
47. FilippakopoulosP, KoflerM, HantschelO, GishGD, GrebienF, et al. (2008) Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation. Cell 134: 793–803.
48. BunkocziG, SalahE, FilippakopoulosP, FedorovO, MullerS, et al. (2007) Structural and functional characterization of the human protein kinase ASK1. Structure 15: 1215–1226.
49. SheridanDL, KongY, ParkerSA, DalbyKN, TurkBE (2008) Substrate discrimination among mitogen-activated protein kinases through distinct docking sequence motifs. Journal of Biological Chemistry 283: 19511–19520.
50. RennefahrtUE, DeaconSW, ParkerSA, DevarajanK, BeeserA, et al. (2007) Specificity profiling of Pak kinases allows identification of novel phosphorylation sites. The Journal of biological chemistry 282: 15667–15678.
51. KikaniCK, AntonysamySA, BonannoJB, RomeroR, ZhangFF, et al. (2010) Structural bases of PAS domain-regulated kinase (PASK) activation in the absence of activation loop phosphorylation. The Journal of biological chemistry 285: 41034–41043.
52. BullockAN, DebreczeniJ, AmosAL, KnappS, TurkBE (2005) Structure and substrate specificity of the Pim-1 kinase. The Journal of biological chemistry 280: 41675–41682.
53. WongA, ZhangYW, JeschkeGR, TurkBE, RudnickG (2012) Cyclic GMP-dependent Stimulation of Serotonin Transport Does Not Involve Direct Transporter Phosphorylation by cGMP-dependent Protein Kinase. Journal of Biological Chemistry 287: 36051–36058.
54. MeeteiAR, MedhurstAL, LingC, XueY, SinghTR, et al. (2005) A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nature genetics 37: 958–963.
55. FaziliZ, SunWP, MittelstaedtS, CohenC, XuXX (1999) Disabled-2 inactivation is an early step in ovarian tumorigenicity. Oncogene 18: 3104–3113.
56. KantarciS, Al-GazaliL, HillRS, DonnaiD, BlackGC, et al. (2007) Mutations in LRP2, which encodes the multiligand receptor megalin, cause Donnai-Barrow and facio-oculo-acoustico-renal syndromes. Nature genetics 39: 957–959.
57. EdgarRC (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic acids research 32: 1792–1797.
58. WardJJ, McGuffinLJ, BrysonK, BuxtonBF, JonesDT (2004) The DISOPRED server for the prediction of protein disorder. Bioinformatics 20: 2138–2139.
59. KentWJ (2002) BLAT–the BLAST-like alignment tool. Genome research 12: 656–664.
60. WangM, WeissM, SimonovicM, HaertingerG, SchrimpfSP, et al. (2012) PaxDb, a Database of Protein Abundance Averages Across All Three Domains of Life. Molecular & Cellular Proteomics 11: 492–500.
61. The R project for Statistical Computing, http://www.r-project.org/.
62. TaylorSS, RadzioandzelmE, HunterT (1995) Protein-Kinases .8. How Do Protein-Kinases Discriminate between Serine Threonine and Tyrosine - Structural Insights from the Insulin-Receptor Protein-Tyrosine Kinase. Faseb Journal 9: 1255–1266.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2014 Číslo 1
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
Najčítanejšie v tomto čísle
- GATA6 Is a Crucial Regulator of Shh in the Limb Bud
- Large Inverted Duplications in the Human Genome Form via a Fold-Back Mechanism
- Genome Sequencing Highlights the Dynamic Early History of Dogs
- Down-Regulation of Rad51 Activity during Meiosis in Yeast Prevents Competition with Dmc1 for Repair of Double-Strand Breaks