Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection

English version České info

Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic differences. This has been supported by differential gene expression analyses in general, but not by the identification of specific regulatory elements responsible for changes in transcription and phenotype. To identify the genetic source of regulatory differences, we mapped DNaseI hypersensitive (DHS) sites, which mark all types of active gene regulatory elements, genome-wide in the same cell type isolated from human, chimpanzee, and macaque. Most DHS sites were conserved among all three species, as expected based on their central role in regulating transcription. However, we found evidence that several hundred DHS sites were gained or lost on the lineages leading to modern human and chimpanzee. Species-specific DHS site gains are enriched near differentially expressed genes, are positively correlated with increased transcription, show evidence of branch-specific positive selection, and overlap with active chromatin marks. Species-specific sequence differences in transcription factor motifs found within these DHS sites are linked with species-specific changes in chromatin accessibility. Together, these indicate that the regulatory elements identified here are genetic contributors to transcriptional and phenotypic differences among primate species.

Vyšlo v časopise: Extensive Evolutionary Changes in Regulatory Element Activity during Human Origins Are Associated with Altered Gene Expression and Positive Selection. PLoS Genet 8(6): e32767. doi:10.1371/journal.pgen.1002789
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002789

Souhrn

Zdroje

1. RobertsonM 2010 The evolution of gene regulation, the RNA universe, and the vexed questions of artefact and noise. BMC Biol 8 97

2. OlsonMVVarkiA 2003 Sequencing the chimpanzee genome: insights into human evolution and disease. Nat Rev Genet 4 20 28

3. SholtisSJNoonanJP 2010 Gene regulation and the origins of human biological uniqueness. Trends Genet 26 110 118

4. KingMCWilsonAC 1975 Evolution at two levels in humans and chimpanzees. Science 188 107 116

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

6. KhaitovichPHellmannIEnardWNowickKLeinweberM 2005 Parallel patterns of evolution in the genomes and transcriptomes of humans and chimpanzees. Science 309 1850 1854

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

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

9. BlekhmanRMarioniJCZumboPStephensMGiladY 2010 Sex-specific and lineage-specific alternative splicing in primates. Genome Res 20 180 189

10. SomelMFranzHYanZLorencAGuoS 2009 Transcriptional neoteny in the human brain. Proc Natl Acad Sci U S A 106 5743 5748

11. XuAGHeLLiZXuYLiM 2010 Intergenic and repeat transcription in human, chimpanzee and macaque brains measured by RNA-Seq. PLoS Comput Biol 6 e1000843 doi:10.1371/journal.pcbi.1000843

12. BabbittCCFedrigoOPfefferleADBoyleAPHorvathJE 2010 Both noncoding and protein-coding RNAs contribute to gene expression evolution in the primate brain. Genome Biol Evol 2 67 79

13. CarrollSB 2008 Evo-devo and an expanding evolutionary synthesis: a genetic theory of morphological evolution. Cell 134 25 36

14. PollardKSSalamaSRKingBKernADDreszerT 2006 Forces shaping the fastest evolving regions in the human genome. PLoS Genet 2 e168 doi:10.1371/journal.pgen.0020168

15. PrabhakarSPoulinFShoukryMAfzalVRubinEM 2006 Close sequence comparisons are sufficient to identify human cis-regulatory elements. Genome Res 16 855 863

16. HaygoodRFedrigoOHansonBYokoyamaKDWrayGA 2007 Promoter regions of many neural- and nutrition-related genes have experienced positive selection during human evolution. Nat Genet 39 1140 1144

17. BoyleAPDavisSShulhaHPMeltzerPMarguliesEH 2008 High-Resolution Mapping and Characterization of Open Chromatin across the Genome. Cell 132 311 322

18. SongLCrawfordGE 2010 DNase-seq: a high-resolution technique for mapping active gene regulatory elements across the genome from mammalian cells. Cold Spring Harb Protoc 2010: pdb prot5384

19. ConsortiumE 2007 Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447 799 816

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

21. XiHShulhaHPLinJMValesTRFuY 2007 Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome. PLoS Genet 3 e136 doi:10.1371/journal.pgen.0030136

22. BlekhmanROshlackAChabotAESmythGKGiladY 2008 Gene regulation in primates evolves under tissue-specific selection pressures. PLoS Genet 4 e1000271 doi:10.1371/journal.pgen.1000271

23. HinrichsASKarolchikDBaertschRBarberGPBejeranoG 2006 The UCSC Genome Browser Database: update 2006. Nucleic Acids Res 34 D590 598

24. CrawfordGEDavisSScacheriPCRenaudGHalawiMJ 2006 DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays. Nat Meth 3 503 509

25. ShibataYCrawfordGE 2009 Mapping regulatory elements by DNaseI hypersensitivity chip (DNase-Chip). Methods Mol Biol 556 177 190

26. RobinsonMDMcCarthyDJSmythGK 2010 edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26 139 140

27. SaboPJHawrylyczMWallaceJCHumbertRYuM 2004 Discovery of functional noncoding elements by digital analysis of chromatin structure. Proc Natl Acad Sci U S A 101 16837 16842

28. SaboPJKuehnMSThurmanRJohnsonBEJohnsonEM 2006 Genome-scale mapping of DNase I sensitivity in vivo using tiling DNA microarrays. Nat Methods 3 511 518

29. ChangHYChiJTDudoitSBondreCvan de RijnM 2002 Diversity, topographic differentiation, and positional memory in human fibroblasts. Proc Natl Acad Sci U S A 99 12877 12882

30. RinnJLBondreCGladstoneHBBrownPOChangHY 2006 Anatomic demarcation by positional variation in fibroblast gene expression programs. PLoS Genet 2 e119 doi:10.1371/journal.pgen.0020119

31. ConsortiumE 2011 A User's Guide to the Encyclopedia of DNA Elements (ENCODE). PLoS Biol 9 e1001046 doi:10.1371/journal.pbio.1001046

32. SongLZhangZGrasfederLLBoyleAPGiresiPG 2011 Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity. Genome Res 21 1757 1767

33. ErnstJKheradpourPMikkelsenTSShoreshNWardLD 2011 Mapping and analysis of chromatin state dynamics in nine human cell types. Nature 473 43 49

34. McLeanCYBristorDHillerMClarkeSLSchaarBT 2010 GREAT improves functional interpretation of cis-regulatory regions. Nat Biotechnol 28 495 501

35. PondSLFrostSDMuseSV 2005 HyPhy: hypothesis testing using phylogenies. Bioinformatics 21 676 679

36. PrabhakarSNoonanJPPaaboSRubinEM 2006 Accelerated evolution of conserved noncoding sequences in humans. Science 314 786

37. PrabhakarSViselAAkiyamaJAShoukryMLewisKD 2008 Human-specific gain of function in a developmental enhancer. Science 321 1346 1350

38. PollardKSSalamaSRLambertNLambotMACoppensS 2006 An RNA gene expressed during cortical development evolved rapidly in humans. Nature 443 167 172

39. SiepelABejeranoGPedersenJSHinrichsASHouM 2005 Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomes. Genome Res 15 1034 1050

40. CooperGMStoneEAAsimenosGGreenEDBatzoglouS 2005 Distribution and intensity of constraint in mammalian genomic sequence. Genome Res 15 901 913

41. ParkerSCHansenLAbaanHOTulliusTDMarguliesEH 2009 Local DNA topography correlates with functional noncoding regions of the human genome. Science 324 389 392

42. BickelPJBoleyNBrownJBHuangHZhangNR 2010 Subsampling methods for genomic inference. The Annals of Applied Statistics 4 1660 1697

43. GraurDLiW-H 2000 Fundamentals of molecular evolution Sunderland, Mass. Sinauer Associates xiv, 481 p.

44. BradleyRKLiXYTrapnellCDavidsonSPachterL 2010 Binding site turnover produces pervasive quantitative changes in transcription factor binding between closely related Drosophila species. PLoS Biol 8 e1000343 doi:10.1371/journal.pbio.1000343

45. SchmidtDWilsonMDBallesterBSchwaliePCBrownGD 2010 Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science 328 1036 1040

46. OdomDTDowellRDJacobsenESGordonWDanfordTW 2007 Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nat Genet 39 730 732

47. MikkelsenTSXuZZhangXWangLGimbleJM 2010 Comparative epigenomic analysis of murine and human adipogenesis. Cell 143 156 169

48. McLeanCYRenoPLPollenAABassanAICapelliniTD 2011 Human-specific loss of regulatory DNA and the evolution of human-specific traits. Nature 471 216 219

49. PapadopoulouVPostigoASanchez-TilloEPorterACWagnerSD 2010 ZEB1 and CtBP form a repressive complex at a distal promoter element of the BCL6 locus. Biochem J 427 541 550

50. ZhangCLMcKinseyTALuJROlsonEN 2001 Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor. J Biol Chem 276 35 39

51. BrawandDSoumillonMNecsuleaAJulienPCsardiG 2011 The evolution of gene expression levels in mammalian organs. Nature 478 343 348

52. WrayGA 2006 The evolution of embryonic gene expression in sea urchins. Integr Comp Biol 46 233 242

53. OrgogozoVMuroNMSternDL 2007 Variation in fiber number of a male-specific muscle between Drosophila species: a genetic and developmental analysis. Evol Dev 9 368 377

54. DegnerJFPaiAAPique-RegiRVeyrierasJBGaffneyDJ 2012 DNase I sensitivity QTLs are a major determinant of human expression variation. Nature 482 390 394

55. HollowayAKLawniczakMKMezeyJGBegunDJJonesCD 2007 Adaptive gene expression divergence inferred from population genomics. PLoS Genet 3 e187 doi:10.1371/journal.pgen.0030187

56. GoodJMHaydenCAWheelerTJ 2006 Adaptive protein evolution and regulatory divergence in Drosophila. Mol Biol Evol 23 1101 1103

57. CainCEBlekhmanRMarioniJCGiladY 2011 Gene expression differences among primates are associated with changes in a histone epigenetic modification. Genetics 187 1225 1234

58. ShaulianEKarinM 2002 AP-1 as a regulator of cell life and death. Nat Cell Biol 4 E131 136

59. KaramouzisMVKonstantinopoulosPAPapavassiliouAG 2007 The activator protein-1 transcription factor in respiratory epithelium carcinogenesis. Mol Cancer Res 5 109 120

60. EferlRWagnerEF 2003 AP-1: a double-edged sword in tumorigenesis. Nat Rev Cancer 3 859 868

61. BiddieSCJohnSSaboPJThurmanREJohnsonTA 2011 Transcription factor AP1 potentiates chromatin accessibility and glucocorticoid receptor binding. Mol Cell 43 145 155

62. BuckMJNobelABLiebJD 2005 ChIPOTle: a user-friendly tool for the analysis of ChIP-chip data. Genome Biol 6 R97

63. LiHDurbinR 2009 Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25 1754 1760

64. BoyleAPGuinneyJCrawfordGEFureyTS 2008 F-Seq: a feature density estimator for high-throughput sequence tags. Bioinformatics 24 2537 2538

65. RobinsonJTThorvaldsdottirHWincklerWGuttmanMLanderES 2011 Integrative genomics viewer. Nat Biotechnol 29 24 26

66. ZhangJNielsenRYangZ 2005 Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level. Mol Biol Evol 22 2472 2479

67. WongWSNielsenR 2004 Detecting selection in noncoding regions of nucleotide sequences. Genetics 167 949 958

68. GilbertW 1978 Why genes in pieces? Nature 271 501

69. PatenBHerreroJBealKFitzgeraldSBirneyE 2008 Enredo and Pecan: genome-wide mammalian consistency-based multiple alignment with paralogs. Genome Res 18 1814 1828

70. PatenBHerreroJFitzgeraldSBealKFlicekP 2008 Genome-wide nucleotide-level mammalian ancestor reconstruction. Genome Res 18 1829 1843

71. t HoenPAAriyurekYThygesenHHVreugdenhilEVossenRH 2008 Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms. Nucleic Acids Res 36 e141