Not so pseudo: the evolutionary history of protein phosphatase 1 regulatory subunit 2 and related pseudogenes

BMC Evolutionary Biology

Pedro J Esteves⁵  Margarida Fardilha⁴  Odete AB da Cruz e Silva¹  Katrin Marcus³  José Melo-Ferreira⁶  Thorsten Muller³  Joana Abrantes²  Luís Korrodi-Gregório⁴ 

[1] Neuroscience Laboratory, Centre for Cell Biology, Biology Department and Health Science Department, University of Aveiro, Aveiro, Portugal;INSERM, U892, Université de Nantes, Nantes, France;Functional Proteomics, Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum, Germany;Signal Transduction Laboratory, Centre for Cell Biology, Biology and Health Science Department, University of Aveiro, Aveiro, Portugal;CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra, Portugal;CIBIO-UP, Centro de Investigação em Biodiversidade e Recursos Genéticos, Universidade do Porto, InBIO, Laboratório Associado, Campus Agrário de Vairão, Vairão, Portugal

关键词: Vertebrates;    Evolution;    Pseudogenization;    Retroposons;    PPP1R2;    PPP1;   

Others  :  1085277
DOI  :  10.1186/1471-2148-13-242

 received in 2013-05-15, accepted in 2013-10-29,  发布年份 2013

【 摘 要 】

Background

Pseudogenes are traditionally considered “dead” genes, therefore lacking biological functions. This view has however been challenged during the last decade. This is the case of the Protein phosphatase 1 regulatory subunit 2 (PPP1R2) or inhibitor-2 gene family, for which several incomplete copies exist scattered throughout the genome.

Results

In this study, the pseudogenization process of PPP1R2 was analyzed. Ten PPP1R2-related pseudogenes (PPP1R2P1-P10), highly similar to PPP1R2, were retrieved from the human genome assembly present in the databases. The phylogenetic analysis of mammalian PPP1R2 and related pseudogenes suggested that PPP1R2P7 and PPP1R2P9 retroposons appeared before the great mammalian radiation, while the remaining pseudogenes are primate-specific and retroposed at different times during Primate evolution. Although considered inactive, four of these pseudogenes seem to be transcribed and possibly possess biological functions. Given the role of PPP1R2 in sperm motility, the presence of these proteins was assessed in human sperm, and two PPP1R2-related proteins were detected, PPP1R2P3 and PPP1R2P9. Signatures of negative and positive selection were also detected in PPP1R2P9, further suggesting a role as a functional protein.

Conclusions

The results show that contrary to initial observations PPP1R2-related pseudogenes are not simple bystanders of the evolutionary process but may rather be at the origin of genes with novel functions.

【 授权许可】

   
2013 Korrodi-Gregório et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Balakirev ES, Ayala FJ: Pseudogenes: are they “junk” or functional DNA? Annu Rev Genet 2003, 37(1):123-151.
• [2]Zheng D, Gerstein MB: The ambiguous boundary between genes and pseudogenes: the dead rise up, or do they? Trends Genet 2007, 23(5):219-224.
• [3]Pei B, Sisu C, Frankish A, Howald C, Habegger L, Mu XJ, Harte R, Balasubramanian S, Tanzer A, Diekhans M, et al.: The GENCODE pseudogene resource. Genome Biol 2012, 13(9):R51. BioMed Central Full Text
• [4]Poliseno L: Pseudogenes: newly discovered players in human cancer. Sci Signal 2012, 5(242):re5.
• [5]McEntee G, Minguzzi S, O'Brien K, Ben Larbi N, Loscher C, O'Fagain C, Parle-McDermott A: The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is expressed and functional. Proc Natl Acad Sci U S A 2011, 108(37):15157-15162.
• [6]McCarrey JR, Thomas K: Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature 1987, 326(6112):501-505.
• [7]Pai HV, Kommaddi RP, Chinta SJ, Mori T, Boyd MR, Ravindranath V: A frameshift mutation and alternate splicing in human brain generate a functional form of the pseudogene cytochrome P4502D7 that demethylates codeine to morphine. J Biol Chem 2004, 279(26):27383-27389.
• [8]Zhang J, Wang X, Li M, Han J, Chen B, Wang B, Dai J: NANOGP8 is a retrogene expressed in cancers. FEBS J 2006, 273(8):1723-1730.
• [9]Sun C, Orozco O, Olson DL, Choi E, Garber E, Tizard R, Szak S, Sanicola M, Carulli JP: CRIPTO3, a presumed pseudogene, is expressed in cancer. Biochem Biophys Res Commun 2008, 377(1):215-220.
• [10]Takahashi K, Mitsui K, Yamanaka S: Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature 2003, 423(6939):541-545.
• [11]Rohozinski J, Edwards CL, Anderson ML: Does expression of the retrogene UTP14c in the ovary pre-dispose women to ovarian cancer? Med Hypotheses 2012, 78(4):446-449.
• [12]Zou M, Baitei EY, Alzahrani AS, Al-Mohanna F, Farid NR, Meyer B, Shi Y: Oncogenic activation of MAP kinase by BRAF pseudogene in thyroid tumors. Neoplasia 2009, 11(1):57-65.
• [13]Kaessmann H, Vinckenbosch N, Long M: RNA-based gene duplication: mechanistic and evolutionary insights. Nat Rev Genet 2009, 10(1):19-31.
• [14]Chiefari E, Iiritano S, Paonessa F, Le Pera I, Arcidiacono B, Filocamo M, Foti D, Liebhaber SA, Brunetti A: Pseudogene-mediated posttranscriptional silencing of HMGA1 can result in insulin resistance and type 2 diabetes. Nat Commun 2010, 1:40.
• [15]Costa V, Esposito R, Aprile M, Ciccodicola A: Non-coding RNA and pseudogenes in neurodegenerative diseases: “the (un)usual suspects”. Front Genet 2012, 3:231.
• [16]DePaoli-Roach AA: Synergistic phosphorylation and activation of ATP-Mg-dependent phosphoprotein phosphatase by F A/GSK-3 and casein kinase II (PC0.7). J Biol Chem 1984, 259(19):12144-12152.
• [17]Aitken A, Holmes CFB, Campbell DG, Resink TJ, Cohen P, Leung CTW, Williams DH: Amino acid sequence at the site on protein phosphatase inhibitor-2, phosphorylated by glycogen synthase kinase-3. Biochim Biophys Acta Protein Struct Mol Enzymol 1984, 790(3):288-291.
• [18]Holmes CF, Kuret J, Chisholm AA, Cohen P: Identification of the sites on rabbit skeletal muscle protein phosphatase inhibitor-2 phosphorylated by casein kinase-II. Biochim Biophys Acta 1986, 870(3):408-416.
• [19]Wang QM, Guan K-L, Roach PJ, DePaoli-Roach AA: Phosphorylation and activation of the ATP-Mg-dependent protein phosphatase by the mitogen-activated protein kinase. J Biol Chem 1995, 270(31):18352-18358.
• [20]Puntoni F, Villamoruzzi E: Phosphorylation of the inhibitor-2 of protein phosphatase-1 by cdc2-cyclin B and GSK3. Biochem Biophys Res Commun 1995, 207(2):732-739.
• [21]Agarwal-Mawal A, Paudel HK: Neuronal Cdc2-like protein kinase (Cdk5/p25) is associated with protein phosphatase 1 and phosphorylates inhibitor-2. J Biol Chem 2001, 276(26):23712-23718.
• [22]Kirchhefer U, Baba HA, Bokník P, Breeden KM, Mavila N, Brüchert N, Justus I, Matus M, Schmitz W, DePaoli-Roach AA, et al.: Enhanced cardiac function in mice overexpressing protein phosphatase inhibitor-2. Cardiovasc Res 2005, 68(1):98-108.
• [23]Yamada M, Ikeda Y, Yano M, Yoshimura K, Nishino S, Aoyama H, Wang L, Aoki H, Matsuzaki M: Inhibition of protein phosphatase 1 by inhibitor-2 gene delivery ameliorates heart failure progression in genetic cardiomyopathy. FASEB J 2006, 20(8):1197-1199.
• [24]Brüchert N, Mavila N, Boknik P, Baba HA, Fabritz L, Gergs U, Kirchhefer U, Kirchhof P, Matus M, Schmitz W, et al.: Inhibitor-2 prevents protein phosphatase 1-induced cardiac hypertrophy and mortality. Am J Physiol Heart Circ Physiol 2008, 295(4):H1539-H1546.
• [25]Eto M, Bock R, Brautigan DL, Linden DJ: Cerebellar long-term synaptic depression requires PKC-mediated activation of CPI-17, a myosin/moesin phosphatase inhibitor. Neuron 2002, 36(6):1145-1158.
• [26]Leach C, Shenolikar S, Brautigan DL: Phosphorylation of phosphatase inhibitor-2 at centrosomes during mitosis. J Biol Chem 2003, 278(28):26015-26020.
• [27]Satinover DL, Leach CA, Stukenberg PT, Brautigan DL: Activation of aurora-A kinase by protein phosphatase inhibitor-2, a bifunctional signaling protein. Proc Natl Acad Sci U S A 2004, 101(23):8625-8630.
• [28]Li M, Stukenberg PT, Brautigan DL: Binding of phosphatase inhibitor-2 to prolyl isomerase pin1 modifies specificity for mitotic phosphoproteins. Biochemistry 2007, 47(1):292-300.
• [29]Wang W, Stukenberg PT, Brautigan DL: Phosphatase inhibitor-2 balances protein phosphatase 1 and aurora B kinase for chromosome segregation and cytokinesis in human retinal epithelial cells. Mol Biol Cell 2008, 19(11):4852-4862.
• [30]Khandani A, Mohtashami M, Camirand A: Inhibitor-2 induced M-phase arrest in Xenopus cycling egg extracts is dependent on MAPK activation. Cell Mol Biol Lett 2011, 16(4):669-688.
• [31]Zambrano CA, Egaña JT, Núñez MT, Maccioni RB, González-Billault C: Oxidative stress promotes τ dephosphorylation in neuronal cells: the roles of cdk5 and PP1. Free Radic Biol Med 2004, 36(11):1393-1402.
• [32]Vijayaraghavan S, Stephens DT, Trautman K, Smith GD, Khatra B, da Cruz e Silva EF, Greengard P: Sperm motility development in the epididymis is associated with decreased glycogen synthase kinase-3 and protein phosphatase 1 activity. Biol Reprod 1996, 54(3):709-718.
• [33]Smith GD, Wolf DP, Trautman KC, da Cruz e Silva EF, Greengard P, Vijayaraghavan S: Primate sperm contain protein phosphatase 1, a biochemical mediator of motility. Biol Reprod 1996, 54(3):719-727.
• [34]Ceulemans H, Stalmans W, Bollen M: Regulator-driven functional diversification of protein phosphatase-1 in eukaryotic evolution. Bioessays 2002, 24(4):371-381.
• [35]Li M, Satinover DL, Brautigan DL: Phosphorylation and functions of inhibitor-2 family of proteins. Biochemistry 2007, 46(9):2380-2389.
• [36]Maestre J, Tchenio T, Dhellin O, Heidmann T: mRNA retroposition in human cells: processed pseudogene formation. EMBO J 1995, 14(24):6333-6338.
• [37]Weiner AM, Deininger PL, Efstratiadis A: Nonviral retroposons: genes, pseudogenes, and transposable elements generated by the reverse flow of genetic information. Annu Rev Biochem 1986, 55(1):631-661.
• [38]Wu I, Moses MA: Cloning of a cDNA encoding an isoform of human protein phosphatase inhibitor 2 from vascularized breast tumor. DNA Seq 2001, 11(6):515-518.
• [39]Yamada Y, Watanabe H, Miura F, Soejima H, Uchiyama M, Iwasaka T, Mukai T, Sakaki Y, Ito T: A comprehensive analysis of allelic methylation status of CpG islands on human chromosome 21q. Genome Res 2004, 14(2):247-266.
• [40]Shirato H, Shima H, Sakashita G, Nakano T, Ito M, Lee EYC, Kikuchi K: Identification and characterization of a novel protein inhibitor of type 1 protein phosphatase. Biochemistry 2000, 39(45):13848-13855.
• [41]Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, et al.: The status, quality, and expansion of the NIH full-length cDNA project: the mammalian gene collection (MGC). Genome Res 2004, 14(10B):2121-2127.
• [42]Eilon T, Barash I: Distinct gene-expression profiles characterize mammary tumors developed in transgenic mice expressing constitutively active and C-terminally truncated variants of STAT5. BMC Genomics 2009, 10(1):231. BioMed Central Full Text
• [43]Fardilha M, Esteves SL, Korrodi-Gregório L, Vintém AP, Domingues SC, Rebelo S, Morrice N, Cohen PT, da Cruz e Silva OA, da Cruz e Silva EF: Identification of the human testis protein phosphatase 1 interactome. Biochem Pharmacol 2011, 82(10):1403-1415.
• [44]Murphy WJ, Eizirik E, O'Brien SJ, Madsen O, Scally M, Douady CJ, Teeling E, Ryder OA, Stanhope MJ, de Jong WW, et al.: Resolution of the early placental mammal radiation using Bayesian phylogenetics. Science 2001, 294(5550):2348-2351.
• [45]Fardilha M, Esteves SLC, Korrodi-Gregório L, Pelech S, da Cruz e Silva OAB, da Cruz e Silva E: Protein phosphatase 1 complexes modulate sperm motility and present novel targets for male infertility. Mol Hum Reprod 2011, 17(8):466-477.
• [46]Mayya V, Han DK: Phosphoproteomics by mass spectrometry: insights, implications, applications and limitations. Expert Rev Proteomics 2009, 6(6):605-618.
• [47]Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJR, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem 2009, 81(11):4493-4501.
• [48]Korrodi-Gregorio L, Ferreira M, Vintem AP, Wu W, Muller T, Marcus K, Vijayaraghavan S, Brautigan DL, da Cruz e Silva OA, Fardilha M, et al.: Identification and characterization of two distinct PPP1R2 isoforms in human spermatozoa. BMC Cell Biol 2013, 14:15. BioMed Central Full Text
• [49]Esteves SL, Domingues SC, da Cruz e Silva OA, Fardilha M, da Cruz e Silva EF: Protein phosphatase 1alpha interacting proteins in the human brain. OMICS 2012, 16(1–2):3-17.
• [50]Montgomery SB, Sammeth M, Gutierrez-Arcelus M, Lach RP, Ingle C, Nisbett J, Guigo R, Dermitzakis ET: Transcriptome genetics using second generation sequencing in a Caucasian population. Nature 2010, 464(7289):773-777.
• [51]Ohshima K, Hattori M, Yada T, Gojobori T, Sakaki Y, Okada N: Whole-genome screening indicates a possible burst of formation of processed pseudogenes and Alu repeats by particular L1 subfamilies in ancestral primates. Genome Biol 2003, 4(11):R74. BioMed Central Full Text
• [52]Kleene KC, Mulligan E, Steiger D, Donohue K, Mastrangelo M-A: The mouse gene encoding the testis-specific isoform of Poly(A) binding protein (Pabp2) is an expressed retroposon: intimations that gene expression in spermatogenic cells facilitates the creation of new genes. J Mol Evol 1998, 47(3):275-281.
• [53]Marques AC, Dupanloup I, Vinckenbosch N, Reymond A, Kaessmann H: Emergence of young human genes after a burst of retroposition in primates. PLoS Biol 2005, 3(11):e357.
• [54]Huang C-J, Lin W-Y, Chang C-M, Choo K-B: Transcription of the rat testis-specific Rtdpoz-T1 and -T2 retrogenes during embryo development: co-transcription and frequent exonisation of transposable element sequences. BMC Mol Biol 2009, 10(1):74. BioMed Central Full Text
• [55]Hurley TD, Yang J, Zhang L, Goodwin KD, Zou Q, Cortese M, Dunker AK, DePaoli-Roach AA: Structural basis for regulation of protein phosphatase 1 by inhibitor-2. J Biol Chem 2007, 282(39):28874-28883.
• [56]Yang J, Hurley TD, DePaoli-Roach AA: Interaction of inhibitor-2 with the catalytic subunit of type 1 protein phosphatase. J Biol Chem 2000, 275(30):22635-22644.
• [57]Varmuza S, Jurisicova A, Okano K, Hudson J, Boekelheide K, Shipp EB: Spermiogenesis is impaired in mice bearing a targeted mutation in the protein phosphatase 1cgamma gene. Dev Biol 1999, 205(1):98-110.
• [58]Chakrabarti R, Cheng L, Puri P, Soler D, Vijayaraghavan S: Protein phosphatase PP1[gamma]2 in sperm morphogenesis and epididymal initiation of sperm motility. Asian J Androl 2007, 9(4):445-452.
• [59]Vinckenbosch N, Dupanloup I, Kaessmann H: Evolutionary fate of retroposed gene copies in the human genome. Proc Natl Acad Sci U S A 2006, 103(9):3220-3225.
• [60]Khachane A, Harrison P: Assessing the genomic evidence for conserved transcribed pseudogenes under selection. BMC Genomics 2009, 10(1):435. BioMed Central Full Text
• [61]Torgerson DG, Singh RS: Enhanced adaptive evolution of sperm-expressed genes on the mammalian X chromosome. Heredity 2006, 96(1):39-44.
• [62]Dorus S, Wasbrough ER, Busby J, Wilkin EC, Karr TL: Sperm proteomics reveals intensified selection on mouse sperm membrane and acrosome genes. Mol Biol Evol 2010, 27(6):1235-1246.
• [63]Pandita A, Balasubramaniam A, Perrin R, Shannon P, Guha A: Malignant and benign ganglioglioma: a pathological and molecular study. Neuro Oncol 2007, 9(2):124-134.
• [64]Pink RC, Wicks K, Caley DP, Punch EK, Jacobs L, Carter DR: Pseudogenes: pseudo-functional or key regulators in health and disease? RNA 2011, 17(5):792-798.
• [65]Hall TA: BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 1999, 41:95-98.
• [66]Posada D: jModelTest: phylogenetic model averaging. Mol Biol Evol 2008, 25(7):1253-1256.
• [67]Zwickl DJ: Genetic algorithm approaches for the phylogenetic analysis of large biological sequence datasets under the maximum likelihood criterion, Dissertation. Austin, TX: University of Texas; 2006.
• [68]Swofford DL: PAUP*. phylogenetic analysis using parsimony (*and other methods) version 4. Sunderland, MA: Sinauer Associates; 2003.
• [69]Hedges SB, Dudley J, Kumar S: TimeTree: a public knowledge-base of divergence times among organisms. Bioinformatics 2006, 22(23):2971-2972.
• [70]Poon AF, Frost SD, Pond SL: Detecting signatures of selection from DNA sequences using Datamonkey. Methods Mol Biol 2009, 537:163-183.
• [71]Pond SL, Frost SD: Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 2005, 21(10):2531-2533.
• [72]Yang Z: PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 2007, 24(8):1586-1591.
• [73]Yang Z, Nielsen R, Goldman N, Pedersen AM: Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 2000, 155(1):431-449.
• [74]Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S: MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 2011, 28(10):2731-2739.
• [75]Zheng D, Frankish A, Baertsch R, Kapranov P, Reymond A, Choo SW, Lu Y, Denoeud F, Antonarakis SE, Snyder M, et al.: Pseudogenes in the ENCODE regions: consensus annotation, analysis of transcription, and evolution. Genome Res 2007, 17(6):839-851.
• [76]World Health Organization: WHO Laboratory for examination of human semen and sperm-cervical mucus interaction. In Collection and examination of human semen. Cambridge: Cambridge University Press; 1999:4-30.
• [77]Thiele H, Glandorf J, Hufnagel P: Bioinformatics strategies in life sciences: from data processing and data warehousing to biological knowledge extraction. J Integr Bioinform 2010, 7(1):141.
• [78]Perkins DN, Pappin DJC, Creasy DM, Cottrell JS: Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis 1999, 20(18):3551-3567.