MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains

English version České info

Among other factors, changes in gene expression on the human evolutionary lineage have been suggested to play an important role in the establishment of human-specific phenotypes. However, the molecular mechanisms underlying these expression changes are largely unknown. Here, we have explored the role of microRNA (miRNA) in the regulation of gene expression divergence among adult humans, chimpanzees, and rhesus macaques, in two brain regions: prefrontal cortex and cerebellum. Using a combination of high-throughput sequencing, miRNA microarrays, and Q-PCR, we have shown that up to 11% of the 325 expressed miRNA diverged significantly between humans and chimpanzees and up to 31% between humans and macaques. Measuring mRNA and protein expression in human and chimpanzee brains, we found a significant inverse relationship between the miRNA and the target genes expression divergence, explaining 2%–4% of mRNA and 4%–6% of protein expression differences. Notably, miRNA showing human-specific expression localize in neurons and target genes that are involved in neural functions. Enrichment in neural functions, as well as miRNA–driven regulation on the human evolutionary lineage, was further confirmed by experimental validation of predicted miRNA targets in two neuroblastoma cell lines. Finally, we identified a signature of positive selection in the upstream region of one of the five miRNA with human-specific expression, miR-34c-5p. This suggests that miR-34c-5p expression change took place after the split of the human and the Neanderthal lineages and had adaptive significance. Taken together these results indicate that changes in miRNA expression might have contributed to evolution of human cognitive functions.

Vyšlo v časopise: MicroRNA Expression and Regulation in Human, Chimpanzee, and Macaque Brains. PLoS Genet 7(10): e32767. doi:10.1371/journal.pgen.1002327
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002327

Souhrn

Zdroje

1. KhaitovichPEnardWLachmannMPaaboS 2006 Evolution of primate gene expression. Nat Rev Genet 7 693 702

2. EnardWKhaitovichPKloseJZollnerSHeissigF 2002 Intra- and interspecific variation in primate gene expression patterns. Science 296 340 343

3. CaceresMLachuerJZapalaMARedmondJCKudoL 2003 Elevated gene expression levels distinguish human from non-human primate brains. Proc Natl Acad Sci U S A 100 13030 13035

4. GiladYOshlackASmythGKSpeedTPWhiteKP 2006 Expression profiling in primates reveals a rapid evolution of human transcription factors. Nature 440 242 245

5. NowickKGernatTAlmaasEStubbsL 2009 Differences in human and chimpanzee gene expression patterns define an evolving network of transcription factors in brain. Proc Natl Acad Sci U S A 106 22358 22363

6. BartelDP 2004 MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116 281 297

7. AmbrosV 2003 MicroRNA pathways in flies and worms: growth, death, fat, stress, and timing. Cell 113 673 676

8. WinterJJungSKellerSGregoryRIDiederichsS 2009 Many roads to maturity: microRNA biogenesis pathways and their regulation. Nat Cell Biol 11 228 234

9. LewisBPShihIHJones-RhoadesMWBartelDPBurgeCB 2003 Prediction of mammalian microRNA targets. Cell 115 787 798

10. LewisBPBurgeCBBartelDP 2005 Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets. Cell 120 15 20

11. NilsenTW 2007 Mechanisms of microRNA-mediated gene regulation in animal cells. Trends Genet 23 243 249

12. HuangJCBabakTCorsonTWChuaGKhanS 2007 Using expression profiling data to identify human microRNA targets. Nat Methods 4 1045 1049

13. HeLHannonGJ 2004 MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet 5 522 531

14. ZhaoYSrivastavaD 2007 A developmental view of microRNA function. Trends Biochem Sci 32 189 197

15. BushatiNCohenSM 2007 microRNA functions. Annu Rev Cell Dev Biol 23 175 205

16. SemendeferiKArmstrongESchleicherAZillesKVan HoesenGW 2001 Prefrontal cortex in humans and apes: a comparative study of area 10. Am J Phys Anthropol 114 224 241

17. RillingJKInselTR 1999 The primate neocortex in comparative perspective using magnetic resonance imaging. J Hum Evol 37 191 223

18. WoodJNGrafmanJ 2003 Human prefrontal cortex: processing and representational perspectives. Nat Rev Neurosci 4 139 147

19. RheadBKarolchikDKuhnRMHinrichsASZweigAS 2010 The UCSC Genome Browser database: update 2010. Nucleic Acids Res 38 D613 619

20. KentWJ 2002 BLAT--the BLAST-like alignment tool. Genome Res 12 656 664

21. AltschulSFGishWMillerWMyersEWLipmanDJ 1990 Basic local alignment search tool. J Mol Biol 215 403 410

22. LarkinMABlackshieldsGBrownNPChennaRMcGettiganPA 2007 Clustal W and Clustal X version 2.0. Bioinformatics 23 2947 2948

23. RobinsonMDMcCarthyDJSmythGK edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26 139 140

24. KhaitovichPMuetzelBSheXLachmannMHellmannI 2004 Regional patterns of gene expression in human and chimpanzee brains. Genome Res 14 1462 1473

25. GrimsonAFarhKKJohnstonWKGarrett-EngelePLimLP 2007 MicroRNA targeting specificity in mammals: determinants beyond seed pairing. Mol Cell 27 91 105

26. BaekDVillenJShinCCamargoFDGygiSP 2008 The impact of microRNAs on protein output. Nature 455 64 71

27. KerteszMIovinoNUnnerstallUGaulUSegalE 2007 The role of site accessibility in microRNA target recognition. Nat Genet 39 1278 1284

28. PlaceRFLiLCPookotDNoonanEJDahiyaR 2008 MicroRNA-373 induces expression of genes with complementary promoter sequences. Proc Natl Acad Sci U S A 105 1608 1613

29. VasudevanSTongYSteitzJA 2007 Switching from repression to activation: microRNAs can up-regulate translation. Science 318 1931 1934

30. TuKYuHHuaYJLiYYLiuL 2009 Combinatorial network of primary and secondary microRNA-driven regulatory mechanisms. Nucleic Acids Res 37 5969 5980

31. FriedmanRCFarhKKBurgeCBBartelDP 2009 Most mammalian mRNAs are conserved targets of microRNAs. Genome Res 19 92 105

32. Huang daWShermanBTLempickiRA 2009 Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 4 44 57

33. PapadopoulosGLAlexiouPMaragkakisMReczkoMHatzigeorgiouAG 2009 DIANA-mirPath: Integrating human and mouse microRNAs in pathways. Bioinformatics 25 1991 1993

34. CookeSFBlissTV 2006 Plasticity in the human central nervous system. Brain 129 1659 1673

35. BlissTVCollingridgeGL 1993 A synaptic model of memory: long-term potentiation in the hippocampus. Nature 361 31 39

36. LiuCTengZQSantistevanNJSzulwachKEGuoW Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell 6 433 444

37. KorzhevskiiDEOtellinVA 2005 Immunocytochemical detection of astrocytes in brain slices in combination with Nissl staining. Neurosci Behav Physiol 35 639 641

38. PilatiNBarkerMPanteleimonitisSDongaRHamannM 2008 A rapid method combining Golgi and Nissl staining to study neuronal morphology and cytoarchitecture. J Histochem Cytochem 56 539 550

39. KringsMStoneASchmitzRWKrainitzkiHStonekingM 1997 Neandertal DNA sequences and the origin of modern humans. Cell 90 19 30

40. GreenREKrauseJBriggsAWMaricicTStenzelU A draft sequence of the Neandertal genome. Science 328 710 722

41. LujambioACalinGAVillanuevaARoperoSSanchez-CespedesM 2008 A microRNA DNA methylation signature for human cancer metastasis. Proc Natl Acad Sci U S A 105 13556 13561

42. ToyotaMSuzukiHSasakiYMaruyamaRImaiK 2008 Epigenetic silencing of microRNA-34b/c and B-cell translocation gene 4 is associated with CpG island methylation in colorectal cancer. Cancer Res 68 4123 4132

43. CannellIGBushell M Regulation of Myc by miR-34c: A mechanism to prevent genomic instability? Cell Cycle 9 2726 2730

44. Minones-MoyanoEPortaSEscaramisGRabionetRIraolaS MicroRNA profiling of Parkinson's disease brains identifies early downregulation of miR-34b/c which modulate mitochondrial function. Hum Mol Genet

45. Lopez-RomeroPGonzalezMACallejasSDopazoAIrizarryRA 2010 Processing of Agilent microRNA array data. BMC Res Notes 3 18

46. FuXFuNGuoSYanZXuY 2009 Estimating accuracy of RNA-Seq and microarrays with proteomics. BMC Genomics 10 161

47. LangmeadBTrapnellCPopMSalzbergSL 2009 Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10 R25

48. ClarkTASchweitzerACChenTXStaplesMKLuG 2007 Discovery of tissue-specific exons using comprehensive human exon microarrays. Genome Biol 8 R64

49. FriedlanderMRAdamidiCHanTLebedevaSIsenbargerTA 2009 High-resolution profiling and discovery of planarian small RNAs. Proc Natl Acad Sci U S A 106 11546 11551

50. HuHYYanZXuYHuHMenzelC 2009 Sequence features associated with microRNA strand selection in humans and flies. BMC Genomics 10 413

51. LiRYuCLiYLamTWYiuSM 2009 SOAP2: an improved ultrafast tool for short read alignment. Bioinformatics 25 1966 1967

52. Griffiths-JonesSSainiHKvan DongenSEnrightAJ 2008 miRBase: tools for microRNA genomics. Nucleic Acids Res 36 D154 158

53. Griffiths-JonesSGrocockRJvan DongenSBatemanAEnrightAJ 2006 miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res 34 D140 144

54. Griffiths-JonesS 2004 The microRNA Registry. Nucleic Acids Res 32 D109 111

55. MiHDongQMuruganujanAGaudetPLewisS PANTHER version 7: improved phylogenetic trees, orthologs and collaboration with the Gene Ontology Consortium. Nucleic Acids Res 38 D204 210

56. KrekAGrunDPoyMNWolfRRosenbergL 2005 Combinatorial microRNA target predictions. Nat Genet 37 495 500

57. BetelDKoppalAAgiusPSanderCLeslieC Comprehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol 11 R90

58. WangXEl NaqaIM 2008 Prediction of both conserved and nonconserved microRNA targets in animals. Bioinformatics 24 325 332

59. MaragkakisMAlexiouPPapadopoulosGLReczkoMDalamagasT 2009 Accurate microRNA target prediction correlates with protein repression levels. BMC Bioinformatics 10 295

60. BandyopadhyaySMitraR 2009 TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples. Bioinformatics 25 2625 2631

61. WenJParkerBJJacobsenAKroghA MicroRNA transfection and AGO-bound CLIP-seq data sets reveal distinct determinants of miRNA action. RNA 17 820 834

62. SaitoTSaetromPA two-step site and mRNA-level model for predicting microRNA targets. BMC Bioinformatics 11 612

63. SilahtarogluANNoltingDDyrskjotLBerezikovEMollerM 2007 Detection of microRNAs in frozen tissue sections by fluorescence in situ hybridization using locked nucleic acid probes and tyramide signal amplification. Nat Protoc 2 2520 2528

64. JankowskyJLDerrickBEPattersonPH 2000 Cytokine responses to LTP induction in the rat hippocampus: a comparison of in vitro and in vivo techniques. Learn Mem 7 400 412

65. WuXWatsonM 2009 CORNA: testing gene lists for regulation by microRNAs. Bioinformatics 25 832 833

66. CelnikerSEDillonLAGersteinMBGunsalusKCHenikoffS 2009 Unlocking the secrets of the genome. Nature 459 927 930

67. HeintzmanNDStuartRKHonGFuYChingCW 2007 Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet 39 311 318

68. CrawfordGEHoltIEWhittleJWebbBDTaiD 2006 Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS). Genome Res 16 123 131