Phosphorylated and nonphosphorylated serine and threonine residues evolve at different rates in mammals

Chun-Chang Chen, Feng-Chi Chen, Wen-Hsiung Li

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Protein phosphorylation plays an important role in the regulation of protein function. Phosphorylated residues are generally assumed to be subject to functional constraint, but it has recently been suggested from a comparison of distantly related vertebrate species that most phosphorylated residues evolve at the rates consistent with the surrounding regions. To resolve the controversy, we infer the ancestral phosphoproteome of human and mouse to compare the evolutionary rates of phosphorylated and nonphosphorylated serine (S), threonine (T), and tyrosine (Y) residues. This approach enables accurate estimation of evolutionary rates as it does not assume deep conservation of phosphorylated residues. We show that phosphorylated S/T residues tend to evolve more slowly than nonphosphorylated S/T residues not only in disordered but also in ordered protein regions, indicating evolutionary conservation of phosphorylated S/T residues in mammals. Thus, phosphorylated S/T residues tend to be subject to stronger functional constraint than nonphosphorylated residues regardless of the protein regions in which they reside. In contrast, phosphorylated Y residues evolve at similar rates as nonphosphorylated ones. We also find that the human lineage has gained more phosphorylated T residues and lost fewer phosphorylated Y residues than the mouse lineage. The cause of the gain/loss imbalance remains a mystery but should be worth exploring. © 2010 The Author.
Original languageEnglish
Pages (from-to)2548-2554
Number of pages7
JournalMolecular Biology and Evolution
Volume27
Issue number11
DOIs
Publication statusPublished - 2010
Externally publishedYes

Fingerprint

Threonine
threonine
serine
Serine
Mammals
mammal
mammals
protein
Proteins
proteins
protein phosphorylation
mice
tyrosine
vertebrates
Tyrosine
Vertebrates
vertebrate
Phosphorylation
rate

Keywords

  • evolutionary rate
  • functional constraint
  • phosphorylated residue
  • protein disordered region
  • serine
  • threonine
  • tyrosine
  • amino acid sequence
  • article
  • genetic conservation
  • human
  • mammal
  • molecular evolution
  • nonhuman
  • protein domain
  • protein function
  • protein phosphorylation
  • Animals
  • Conserved Sequence
  • Evolution, Molecular
  • Humans
  • Mammals
  • Mice
  • Phosphorylation
  • Phosphoserine
  • Phosphothreonine
  • Phylogeny
  • Mammalia
  • Vertebrata

Cite this

Phosphorylated and nonphosphorylated serine and threonine residues evolve at different rates in mammals. / Chen, Chun-Chang; Chen, Feng-Chi; Li, Wen-Hsiung.

In: Molecular Biology and Evolution, Vol. 27, No. 11, 2010, p. 2548-2554.

Research output: Contribution to journalArticle

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abstract = "Protein phosphorylation plays an important role in the regulation of protein function. Phosphorylated residues are generally assumed to be subject to functional constraint, but it has recently been suggested from a comparison of distantly related vertebrate species that most phosphorylated residues evolve at the rates consistent with the surrounding regions. To resolve the controversy, we infer the ancestral phosphoproteome of human and mouse to compare the evolutionary rates of phosphorylated and nonphosphorylated serine (S), threonine (T), and tyrosine (Y) residues. This approach enables accurate estimation of evolutionary rates as it does not assume deep conservation of phosphorylated residues. We show that phosphorylated S/T residues tend to evolve more slowly than nonphosphorylated S/T residues not only in disordered but also in ordered protein regions, indicating evolutionary conservation of phosphorylated S/T residues in mammals. Thus, phosphorylated S/T residues tend to be subject to stronger functional constraint than nonphosphorylated residues regardless of the protein regions in which they reside. In contrast, phosphorylated Y residues evolve at similar rates as nonphosphorylated ones. We also find that the human lineage has gained more phosphorylated T residues and lost fewer phosphorylated Y residues than the mouse lineage. The cause of the gain/loss imbalance remains a mystery but should be worth exploring. {\circledC} 2010 The Author.",
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author = "Chun-Chang Chen and Feng-Chi Chen and Wen-Hsiung Li",
note = "被引用次數:19 Export Date: 21 March 2016 CODEN: MBEVE 通訊地址: Li, W.-H.; Department of Ecology and Evolution, University of ChicagoUnited States; 電子郵件: whli@uchicago.edu 化學物質/CAS: serine, 56-45-1, 6898-95-9; threonine, 36676-50-3, 72-19-5; tyrosine, 16870-43-2, 55520-40-6, 60-18-4; Phosphoserine, 17885-08-4; Phosphothreonine, 1114-81-4 參考文獻: Aivaliotis, M., MacEk, B., Gnad, F., Reichelt, P., Mann, M., Oesterhelt, D., Ser/Thr/Tyr protein phosphorylation in the archaeon Halobacterium salinarum\a representative of the third domain of life (2009) PLoS One, 4, pp. e4777; Blenis, J., Resh, M.D., Subcellular localization specified by protein acylation and phosphorylation (1993) Curr Opin Cell Biol, 5, pp. 984-989; Boekhorst, J., Van Breukelen, B., Heck, A.J., Snel, B., Comparative phosphoproteomics reveals evolutionary and functional conservation of phosphorylation across eukaryotes (2008) Genome Biol, 9, pp. R144; Brown, C.J., Takayama, S., Campen, A.M., Vise, P., Marshall, T.W., Oldfield, C.J., Williams, C.J., Dunker, A.K., Evolutionary rate heterogeneity in proteins with long disordered regions (2002) J Mol Evol, 55, pp. 104-110; Diella, F., Gould, C.M., Chica, C., Via, A., Gibson, T.J., Phospho. ELM: A database of phosphorylation sites-update 2008 (2008) Nucleic Acids Res, 36, pp. D240-D244; Do, C.B., Mahabhashyam, M.S., Brudno, M., Batzoglou, S., ProbCons: Probabilistic consistency-based multiple sequence alignment (2005) Genome Res, 15, pp. 330-340; Dunker, A.K., Brown, C.J., Lawson, J.D., Iakoucheva, L.M., Obradovic, Z., Intrinsic disorder and protein function (2002) Biochemistry, 41, pp. 6573-6582; Edgar, R.C., MUSCLE: Multiple sequence alignment with high accuracy and high throughput (2004) Nucleic Acids Res, 32, pp. 1792-1797; Gnad, F., Ren, S., Cox, J., Olsen, J.V., MacEk, B., Oroshi, M., Mann, M., PHOSIDA (phosphorylation site database): Management, structural and evolutionary investigation, and prediction of phosphosites (2007) Genome Biol, 8, pp. R250; Iakoucheva, L.M., Radivojac, P., Brown, C.J., O'Connor, T.R., Sikes, J.G., Obradovic, Z., Dunker, A.K., The importance of intrinsic disorder for protein phosphorylation (2004) Nucleic Acids Res, 32, pp. 1037-1049; Jimenez, J.L., Hegemann, B., Hutchins, J.R., Peters, J.M., Durbin, R., A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database (2007) Genome Biol, 8, pp. R90; Keshava Prasad, T.S., Goel, R., Kandasamy, K., Human Protein Reference Database-2009 update (2009) Nucleic Acids Res, 37, pp. D767-D772. , (30 co-authors); Landry, C.R., Levy, E.D., Michnick, S.W., Weak functional constraints on phosphoproteomes (2009) Trends Genet, 25, pp. 193-197; Lin, Y.S., Hsu, W.L., Hwang, J.K., Li, W.H., Proportion of solventexposed amino acids in a protein and rate of protein evolution (2007) Mol Biol Evol, 24, pp. 1005-1011; Linding, R., Russell, R.B., Neduva, V., Gibson, T.J., GlobPlot: Exploring protein sequences for globularity and disorder (2003) Nucleic Acids Res, 31, pp. 3701-3708; Shaywitz, A.J., Dove, S.L., Greenberg, M.E., Hochschild, A., Analysis of phosphorylation-dependent protein-protein interactions using a bacterial two-hybrid system (2002) Sci STKE, 2002, pp. pl11; Trinidad, J.C., Thalhammer, A., Specht, C.G., Lynn, A.J., Baker, P.R., Schoepfer, R., Burlingame, A.L., Quantitative analysis of synaptic phosphorylation and protein expression (2008) Mol Cell Proteomics, 7, pp. 684-696; Wagner, M., Adamczak, R., Porollo, A., Meller, J., Linear regression models for solvent accessibility prediction in proteins (2005) Journal of Computational Biology, 12 (3), pp. 355-369. , DOI 10.1089/cmb.2005.12.355; Ward, J.J., Sodhi, J.S., McGuffin, L.J., Buxton, B.F., Jones, D.T., Prediction and functional analysis of native disorder in proteins from the three kingdoms of life (2004) J Mol Biol, 337, pp. 635-645; Wong, Y.H., Lee, T.Y., Liang, H.K., Huang, C.M., Wang, T.Y., Yang, Y.H., Chu, C.H., Hwang, J.K., Kinase Phos 2. 0: A web server for identifying protein kinase-specific phosphorylation sites based on sequences and coupling patterns (2007) Nucleic Acids Res, 35, pp. W588-W594; Xue, Y., Ren, J., Gao, X., Jin, C., Wen, L., Yao, X., GPS 2. 0, a tool to predict kinase-specific phosphorylation sites in hierarchy (2008) Mol Cell Proteomics, 7, pp. 1598-1608; Yang, Z., PAML: A program package for phylogenetic analysis by maximum likelihood (1997) Comput Appl Biosci, 13, pp. 555-556",
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TY - JOUR

T1 - Phosphorylated and nonphosphorylated serine and threonine residues evolve at different rates in mammals

AU - Chen, Chun-Chang

AU - Chen, Feng-Chi

AU - Li, Wen-Hsiung

N1 - 被引用次數:19 Export Date: 21 March 2016 CODEN: MBEVE 通訊地址: Li, W.-H.; Department of Ecology and Evolution, University of ChicagoUnited States; 電子郵件: whli@uchicago.edu 化學物質/CAS: serine, 56-45-1, 6898-95-9; threonine, 36676-50-3, 72-19-5; tyrosine, 16870-43-2, 55520-40-6, 60-18-4; Phosphoserine, 17885-08-4; Phosphothreonine, 1114-81-4 參考文獻: Aivaliotis, M., MacEk, B., Gnad, F., Reichelt, P., Mann, M., Oesterhelt, D., Ser/Thr/Tyr protein phosphorylation in the archaeon Halobacterium salinarum\a representative of the third domain of life (2009) PLoS One, 4, pp. e4777; Blenis, J., Resh, M.D., Subcellular localization specified by protein acylation and phosphorylation (1993) Curr Opin Cell Biol, 5, pp. 984-989; Boekhorst, J., Van Breukelen, B., Heck, A.J., Snel, B., Comparative phosphoproteomics reveals evolutionary and functional conservation of phosphorylation across eukaryotes (2008) Genome Biol, 9, pp. R144; Brown, C.J., Takayama, S., Campen, A.M., Vise, P., Marshall, T.W., Oldfield, C.J., Williams, C.J., Dunker, A.K., Evolutionary rate heterogeneity in proteins with long disordered regions (2002) J Mol Evol, 55, pp. 104-110; Diella, F., Gould, C.M., Chica, C., Via, A., Gibson, T.J., Phospho. ELM: A database of phosphorylation sites-update 2008 (2008) Nucleic Acids Res, 36, pp. D240-D244; Do, C.B., Mahabhashyam, M.S., Brudno, M., Batzoglou, S., ProbCons: Probabilistic consistency-based multiple sequence alignment (2005) Genome Res, 15, pp. 330-340; Dunker, A.K., Brown, C.J., Lawson, J.D., Iakoucheva, L.M., Obradovic, Z., Intrinsic disorder and protein function (2002) Biochemistry, 41, pp. 6573-6582; Edgar, R.C., MUSCLE: Multiple sequence alignment with high accuracy and high throughput (2004) Nucleic Acids Res, 32, pp. 1792-1797; Gnad, F., Ren, S., Cox, J., Olsen, J.V., MacEk, B., Oroshi, M., Mann, M., PHOSIDA (phosphorylation site database): Management, structural and evolutionary investigation, and prediction of phosphosites (2007) Genome Biol, 8, pp. R250; Iakoucheva, L.M., Radivojac, P., Brown, C.J., O'Connor, T.R., Sikes, J.G., Obradovic, Z., Dunker, A.K., The importance of intrinsic disorder for protein phosphorylation (2004) Nucleic Acids Res, 32, pp. 1037-1049; Jimenez, J.L., Hegemann, B., Hutchins, J.R., Peters, J.M., Durbin, R., A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database (2007) Genome Biol, 8, pp. R90; Keshava Prasad, T.S., Goel, R., Kandasamy, K., Human Protein Reference Database-2009 update (2009) Nucleic Acids Res, 37, pp. D767-D772. , (30 co-authors); Landry, C.R., Levy, E.D., Michnick, S.W., Weak functional constraints on phosphoproteomes (2009) Trends Genet, 25, pp. 193-197; Lin, Y.S., Hsu, W.L., Hwang, J.K., Li, W.H., Proportion of solventexposed amino acids in a protein and rate of protein evolution (2007) Mol Biol Evol, 24, pp. 1005-1011; Linding, R., Russell, R.B., Neduva, V., Gibson, T.J., GlobPlot: Exploring protein sequences for globularity and disorder (2003) Nucleic Acids Res, 31, pp. 3701-3708; Shaywitz, A.J., Dove, S.L., Greenberg, M.E., Hochschild, A., Analysis of phosphorylation-dependent protein-protein interactions using a bacterial two-hybrid system (2002) Sci STKE, 2002, pp. pl11; Trinidad, J.C., Thalhammer, A., Specht, C.G., Lynn, A.J., Baker, P.R., Schoepfer, R., Burlingame, A.L., Quantitative analysis of synaptic phosphorylation and protein expression (2008) Mol Cell Proteomics, 7, pp. 684-696; Wagner, M., Adamczak, R., Porollo, A., Meller, J., Linear regression models for solvent accessibility prediction in proteins (2005) Journal of Computational Biology, 12 (3), pp. 355-369. , DOI 10.1089/cmb.2005.12.355; Ward, J.J., Sodhi, J.S., McGuffin, L.J., Buxton, B.F., Jones, D.T., Prediction and functional analysis of native disorder in proteins from the three kingdoms of life (2004) J Mol Biol, 337, pp. 635-645; Wong, Y.H., Lee, T.Y., Liang, H.K., Huang, C.M., Wang, T.Y., Yang, Y.H., Chu, C.H., Hwang, J.K., Kinase Phos 2. 0: A web server for identifying protein kinase-specific phosphorylation sites based on sequences and coupling patterns (2007) Nucleic Acids Res, 35, pp. W588-W594; Xue, Y., Ren, J., Gao, X., Jin, C., Wen, L., Yao, X., GPS 2. 0, a tool to predict kinase-specific phosphorylation sites in hierarchy (2008) Mol Cell Proteomics, 7, pp. 1598-1608; Yang, Z., PAML: A program package for phylogenetic analysis by maximum likelihood (1997) Comput Appl Biosci, 13, pp. 555-556

PY - 2010

Y1 - 2010

N2 - Protein phosphorylation plays an important role in the regulation of protein function. Phosphorylated residues are generally assumed to be subject to functional constraint, but it has recently been suggested from a comparison of distantly related vertebrate species that most phosphorylated residues evolve at the rates consistent with the surrounding regions. To resolve the controversy, we infer the ancestral phosphoproteome of human and mouse to compare the evolutionary rates of phosphorylated and nonphosphorylated serine (S), threonine (T), and tyrosine (Y) residues. This approach enables accurate estimation of evolutionary rates as it does not assume deep conservation of phosphorylated residues. We show that phosphorylated S/T residues tend to evolve more slowly than nonphosphorylated S/T residues not only in disordered but also in ordered protein regions, indicating evolutionary conservation of phosphorylated S/T residues in mammals. Thus, phosphorylated S/T residues tend to be subject to stronger functional constraint than nonphosphorylated residues regardless of the protein regions in which they reside. In contrast, phosphorylated Y residues evolve at similar rates as nonphosphorylated ones. We also find that the human lineage has gained more phosphorylated T residues and lost fewer phosphorylated Y residues than the mouse lineage. The cause of the gain/loss imbalance remains a mystery but should be worth exploring. © 2010 The Author.

AB - Protein phosphorylation plays an important role in the regulation of protein function. Phosphorylated residues are generally assumed to be subject to functional constraint, but it has recently been suggested from a comparison of distantly related vertebrate species that most phosphorylated residues evolve at the rates consistent with the surrounding regions. To resolve the controversy, we infer the ancestral phosphoproteome of human and mouse to compare the evolutionary rates of phosphorylated and nonphosphorylated serine (S), threonine (T), and tyrosine (Y) residues. This approach enables accurate estimation of evolutionary rates as it does not assume deep conservation of phosphorylated residues. We show that phosphorylated S/T residues tend to evolve more slowly than nonphosphorylated S/T residues not only in disordered but also in ordered protein regions, indicating evolutionary conservation of phosphorylated S/T residues in mammals. Thus, phosphorylated S/T residues tend to be subject to stronger functional constraint than nonphosphorylated residues regardless of the protein regions in which they reside. In contrast, phosphorylated Y residues evolve at similar rates as nonphosphorylated ones. We also find that the human lineage has gained more phosphorylated T residues and lost fewer phosphorylated Y residues than the mouse lineage. The cause of the gain/loss imbalance remains a mystery but should be worth exploring. © 2010 The Author.

KW - evolutionary rate

KW - functional constraint

KW - phosphorylated residue

KW - protein disordered region

KW - serine

KW - threonine

KW - tyrosine

KW - amino acid sequence

KW - article

KW - genetic conservation

KW - human

KW - mammal

KW - molecular evolution

KW - nonhuman

KW - protein domain

KW - protein function

KW - protein phosphorylation

KW - Animals

KW - Conserved Sequence

KW - Evolution, Molecular

KW - Humans

KW - Mammals

KW - Mice

KW - Phosphorylation

KW - Phosphoserine

KW - Phosphothreonine

KW - Phylogeny

KW - Mammalia

KW - Vertebrata

U2 - 10.1093/molbev/msq142

DO - 10.1093/molbev/msq142

M3 - Article

VL - 27

SP - 2548

EP - 2554

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 11

ER -