Distinct Functional Constraints Partition Sequence Conservation in a -Regulatory Element

English version České info

Different functional constraints contribute to different evolutionary rates across genomes. To understand why some sequences evolve faster than others in a single cis-regulatory locus, we investigated function and evolutionary dynamics of the promoter of the Caenorhabditis elegans unc-47 gene. We found that this promoter consists of two distinct domains. The proximal promoter is conserved and is largely sufficient to direct appropriate spatial expression. The distal promoter displays little if any conservation between several closely related nematodes. Despite this divergence, sequences from all species confer robustness of expression, arguing that this function does not require substantial sequence conservation. We showed that even unrelated sequences have the ability to promote robust expression. A prominent feature shared by all of these robustness-promoting sequences is an AT-enriched nucleotide composition consistent with nucleosome depletion. Because general sequence composition can be maintained despite sequence turnover, our results explain how different functional constraints can lead to vastly disparate rates of sequence divergence within a promoter.

Vyšlo v časopise: Distinct Functional Constraints Partition Sequence Conservation in a -Regulatory Element. PLoS Genet 7(6): e32767. doi:10.1371/journal.pgen.1002095
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002095

Souhrn

Zdroje

1. XieXMikkelsenTSGnirkeALindblad-TohKKellisM 2007 Systematic discovery of regulatory motifs in conserved regions of the human genome, including thousands of CTCF insulator sites. Proc Natl Acad Sci U S A 104 17 7145 7150

2. BejeranoGPheasantMMakuninIStephenSKentWJ 2004 Ultraconserved elements in the human genome. Science 304 5675 1321 1325

3. BoffelliDNobregaMARubinEM 2004 Comparative genomics at the vertebrate extremes. Nature Reviews Genetics 5 6 456 465

4. PennacchioLARubinEM 2001 Genomic strategies to identify mammalian regulatory sequences. Nature Reviews Genetics 2 2 100 109

5. AparicioSMorrisonAGouldAGilthorpeJChaudhuriC 1995 Detecting conserved regulatory elements with the model genome of the japanese puffer fish, fugu rubripes. Proc Natl Acad Sci U S A 92 5 1684 1688

6. BlowMJMcCulleyDJLiZZhangTAkiyamaJA 2010 ChIP-seq identification of weakly conserved heart enhancers. Nat Genet 42 9 806-U107

7. RitterDILiQKostkaDPollardKSGuoS 2010 The importance of being cis: Evolution of orthologous fish and mammalian enhancer activity. Mol Biol Evol 27 10 2322 2332

8. McGaugheyDMVintonRMHuynhJAl-SaifABeerMA 2008 Metrics of sequence constraint overlook regulatory sequences in an exhaustive analysis at phox2b. Genome Res 18 2 252 260

9. MarguliesEHCooperGMAsimenosGThomasDJDeweyCN 2007 Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome. Genome Res 17 6 760 774

10. HareEEPetersonBKIyerVNMeierREisenMB 2008 Sepsid even-skipped enhancers are functionally conserved in drosophila despite lack of sequence conservation. PLoS Genet 4 e1000106 doi:10.1371/journal.pgen.1000106

11. FisherSGriceEAVintonRMBesslingSLMcCallionAS 2006 Conservation of RET regulatory function from human to zebrafish without sequence similarity. Science 312 5771 276 279

12. RomanoLAWrayGA 2003 Conservation of Endo16 expression in sea urchins despite evolutionary divergence in both cis and trans-acting components of transcriptional regulation. Development 130 17 4187 4199

13. WrayGAHahnMWAbouheifEBalhoffJPPizerM 2003 The evolution of transcriptional regulation in eukaryotes. Mol Biol Evol 20 9 1377 1419

14. SwansonCIEvansNCBaroloS 2010 Structural rules and complex regulatory circuitry constrain expression of a notch- and EGFR-regulated eye enhancer. Developmental Cell 18 3 359 370

15. NokesEBVan Der LindenAMWinslowCMukhopadhyaySMaK 2009 Cis-regulatory mechanisms of gene expression in an olfactory neuron type in caenorhabditis elegans. Developmental Dynamics 238 12 3080 3092

16. CrockerJTamoriYErivesA 2008 Evolution acts on enhancer organization to fine-tune gradient threshold readouts. PLoS Biol 6 e263 doi:10.1371/journal.pbio.0060263

17. JohnsonDSDavidsonBBrownCDSmithWCSidowA 2004 Noncoding regulatory sequences of gona exhibit strong correspondence between evolutionary constraint and functional importance. Genome Res 14 12 2448 2456

18. SmallSArnostiDNLevineM 1993 Spacing ensures autonomous expression of different stripe enhancers in the even-skipped promoter. Development 119 3 767 772

19. BrownCDJohnsonDSSidowA 2007 Functional architecture and evolution of transcriptional elements that drive gene coexpression. Science 317 5844 1557 1560

20. PapatsenkoDLevineM 2007 A rationale for the enhanceosome and other evolutionarily constrained enhancers. Current Biology 17 22 R955 R957

21. ErivesALevineM 2004 Coordinate enhancers share common organizational features in the drosophila genome. Proc Natl Acad Sci U S A 101 11 3851 3856

22. WeirauchMTHughesTR 2010 Conserved expression without conserved regulatory sequence: The more things change, the more they stay the same. Trends in Genetics 26 2 66 74

23. ArnostiDNKulkarniMM 2005 Transcriptional enhancers: Intelligent enhanceosomes or flexible billboards? J Cell Biochem 94 5 890 898

24. BradleyRKLiXTrapnellCDavidsonSPachterL 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

25. GiladYRifkinSAPritchardJK 2008 Revealing the architecture of gene regulation: The promise of eQTL studies. Trends in Genetics 24 8 408 415

26. PriceALPattersonNHancksDCMyersSReichD 2008 Effects of cis and trans genetic ancestry on gene expression in african americans. PLoS Genet 4 e1000294 doi:10.1371/journal.pgen.1000294

27. RajARifkinSAAndersenEvan OudenaardenA 2010 Variability in gene expression underlies incomplete penetrance. Nature 463 7283 913-U84

28. MaselJSiegalML 2009 Robustness: Mechanisms and consequences. Trends in Genetics 25 9 395 403

29. BraendleCFelixM 2008 Plasticity and errors of a robust developmental system in different environments. Developmental Cell 15 5 714 724

30. FelixMWagnerA 2008 Robustness and evolution: Concepts, insights and challenges from a developmental model system. Heredity 100 2 132 140

31. SiegalMLBergmanA 2002 Waddington's canalization revisited: Developmental stability and evolution. Proc Natl Acad Sci U S A 99 16 10528 10532

32. ManuSurkovaSSpirovAVGurskyVVJanssensH 2009 Canalization of gene expression in the drosophila blastoderm by gap gene cross regulation. PLoS Biol 7 e1000049 doi:10.1371/journal.pbio.1000049

33. SzoellosiGJDerenyiI 2009 Congruent evolution of genetic and environmental robustness in micro-RNA. Mol Biol Evol 26 4 867 874

34. HongJHendrixDALevineMS 2008 Shadow enhancers as a source of evolutionary novelty. Science 321 5894 1314 1314

35. FrankelNDavisGKVargasDWangSPayreF 2010 Phenotypic robustness conferred by apparently redundant transcriptional enhancers. Nature 466 7305 490-U8

36. PerryMWBoettigerANBothmaJPLevineM 2010 Shadow enhancers foster robustness of drosophila gastrulation. Current Biology 20 17 1562 1567

37. LiXCassidyJJReinkeCAFischboeckSCarthewRW 2009 A MicroRNA imparts robustness against environmental fluctuation during development. Cell 137 2 273 282

38. HerranzHCohenSM 2010 MicroRNAs and gene regulatory networks: Managing the impact of noise in biological systems. Genes Dev 24 13 1339 1344

39. KiontkeKGavinNPRaynesYRoehrigCPianoF 2004 Caenorhabditis phylogeny predicts convergence of hermaphroditism and extensive intron loss. Proc Natl Acad Sci U S A 101 24 9003 9008

40. McIntireSLReimerRJSchuskeKEdwardsRHJorgensenEM 1997 Identification and characterization of the vesicular GABA transporter. Nature 389 6653 870 876

41. RuvinskyIRuvkunG 2003 Functional tests of enhancer conservation between distantly related species. Development 130 21 5133 5142

42. KagawaHGengyoKMclachlanADBrennerSKarnJ 1989 Paramyosin gene (unc-15) of caenorhabditis-elegans - molecular-cloning, nucleotide-sequence and models for thick filament structure. J Mol Biol 207 2 311 333

43. EastmanCHorvitzHRJinYS 1999 Coordinated transcriptional regulation of the unc-25 glutamic acid decarboxylase and the unc-47 GABA vesicular transporter by the caenorhabditis elegans UNC-30 homeodomain protein. Journal of Neuroscience 19 15 6225 6234

44. SegalEWidomJ 2009 What controls nucleosome positions? Trends in Genetics 25 8 335 343

45. GuertinMJLisJT 2010 Chromatin landscape dictates HSF binding to target DNA elements. PLoS Genet 6 e1001114 doi:10.1371/journal.pgen.1001114

46. KhoueiryPRothbacherUOhtsukaYDaianFFrangulianE 2010 A cis-regulatory signature in ascidians and flies, independent of transcription factor binding sites. Current Biology 20 9 792 802

47. ValouevAIchikawaJTonthatTStuartJRanadeS 2008 A high-resolution, nucleosome position map of C. elegans reveals a lack of universal sequence-dictated positioning. Genome Res 18 7 1051 1063

48. TiroshISigalNBarkaiN 2010 Divergence of nucleosome positioning between two closely related yeast species: Genetic basis and functional consequences. Molecular Systems Biology 6 365

49. TsankovAMThompsonDASochaARegevARandoOJ 2010 The role of nucleosome positioning in the evolution of gene regulation. PLoS Biol 8 e1000414 doi:10.1371/journal.pbio.1000414

50. ChoiJKKimY 2009 Intrinsic variability of gene expression encoded in nucleosome positioning sequences. Nat Genet 41 4 498 503

51. GibertJKarchFSchloettererC 2011 Segregating variation in the polycomb group gene cramped alters the effect of temperature on multiple traits. PLoS Genet 7 e1001280 doi:10.1371/journal.pgen.1001280

52. KenigsbergEBarASegalETanayA 2010 Widespread compensatory evolution conserves DNA-encoded nucleosome organization in yeast. PLoS Comput Biol 6 e1001039 doi:10.1371/journal.pcbi.1001039

53. CooperGMBrownCD 2008 Qualifying the relationship between sequence conservation and molecular function. Genome Res 18 2 201 205

54. TrueJRHaagES 2001 Developmental system drift and flexibility in evolutionary trajectories. Evol Dev 3 2 109 119

55. GranatoMSchnabelHSchnabelR 1994 Pha-1, a selectable marker for gene-transfer in C-elegans. Nucleic Acids Res 22 9 1762 1763

56. Frokjaer-JensenCDavisMWHopkinsCENewmanBJThummelJM 2008 Single-copy insertion of transgenes in caenorhabditis elegans. Nat Genet 40 11 1375 1383