title: Microevolution of cis-regulatory elements: an example from the pair-rule segmentation gene fushi tarazu in the Drosophila melanogaster subgroup.
abstract: The importance of non-coding DNAs that control transcription is ever noticeable, but the characterization and analysis of the evolution of such DNAs presents challenges not found in the analysis of coding sequences. In this study of the cis-regulatory elements of the pair rule segmentation gene fushi tarazu (ftz) I report the DNA sequences of ftz's zebra element (promoter) and a region containing the proximal enhancer from a total of 45 fly lines belonging to several populations of the species Drosophila melanogaster, D. simulans, D. sechellia, D. mauritiana, D. yakuba, D. teissieri, D. orena and D. erecta. Both elements evolve at slower rate than ftz synonymous sites, thus reflecting their functional importance. The promoter evolves more slowly than the average for ftz's coding sequence while, on average, the enhancer evolves more rapidly, suggesting more functional constraint and effective purifying selection on the former. Comparative analysis of the number and nature of base substitutions failed to detect significant evidence for positive/adaptive selection in transcription-factor-binding sites. These seem to evolve at similar rates to regions not known to bind transcription factors. Although this result reflects the evolutionary flexibility of the transcription factor binding sites, it also suggests a complex and still not completely understood nature of even the characterized cis-regulatory sequences. The latter seem to contain more functional parts than those currently identified, some of which probably transcription factor binding. This study illustrates ways in which functional assignments of sequences within cis-acting sequences can be used in the search for adaptive evolution, but also highlights difficulties in how such functional assignment and analysis can be carried out.
authors.affiliation: Departamento de Genética, Facultad de Ciencias, Universidad de Granada, Granada, Spain. mbakkali@ugr.es
authors.forename: Mohammed
authors.initials: M
authors.lastname: Bakkali
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics*; D004331:Drosophila melanogaster / Q000235:genetics*; D019143:Evolution, Molecular; D051717:Fushi Tarazu Transcription Factors / Q000235:genetics*; D016013:Likelihood Functions; D008969:Molecular Sequence Data; D010802:Phylogeny; D012045:Regulatory Sequences, Nucleic Acid
chemical_list: D029721:Drosophila Proteins; D051717:Fushi Tarazu Transcription Factors; C497169:ftz protein, Drosophila
references.citation: Mol Biol Evol. 2003 Sep;20(9):1377-419
references.pmid: 12777501
references.citation: Mol Biol Evol. 2011 Oct;28(10):2731-9
references.pmid: 21546353
references.citation: Pac Symp Biocomput. 1997;:477-85
references.pmid: 9390316
references.citation: Nature. 2003 Aug 21;424(6951):935-8
references.pmid: 12931187
references.citation: Nucleic Acids Res. 2003 Jul 1;31(13):3576-9
references.pmid: 12824369
references.citation: Mol Biol Evol. 1999 Feb;16(2):253-65
references.pmid: 10028291
references.citation: Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11030-5
references.pmid: 15258291
references.citation: Cell. 1985 Dec;43(3 Pt 2):603-13
references.pmid: 3935327
references.citation: Theor Popul Biol. 1975 Apr;7(2):256-76
references.pmid: 1145509
references.citation: Curr Biol. 1994 Dec 1;4(12):1165-6
references.pmid: 7704590
references.citation: Mol Biol Evol. 1995 May;12(3):391-404
references.pmid: 7739381
references.citation: Dev Biol. 2000 May 1;221(1):148-67
references.pmid: 10772798
references.citation: J Biol Chem. 2007 Jun 1;282(22):15981-94
references.pmid: 17426024
references.citation: Mol Biol Evol. 2008 Sep;25(9):1825-34
references.pmid: 18515263
references.citation: Nature. 1991 Jun 20;351(6328):652-4
references.pmid: 1904993
references.citation: Nature. 1998 Dec 3;396(6710):463-6
references.pmid: 9853753
references.citation: Methods Mol Biol. 2007;395:367-80
references.pmid: 17993686
references.citation: Novartis Found Symp. 2007;284:191-200; discussion 200-6
references.pmid: 17710854
references.citation: Nature. 2000 Feb 3;403(6769):564-7
references.pmid: 10676967
references.citation: Dev Biol. 2009 Mar 15;327(2):578-89
references.pmid: 19135437
references.citation: J Mol Evol. 1981;17(6):368-76
references.pmid: 7288891
references.citation: Development. 2004 Sep;131(17):4251-61
references.pmid: 15280214
references.citation: Mol Cell Biol. 1998 Jun;18(6):3384-94
references.pmid: 9584179
references.citation: Genomics. 2004 Sep;84(3):511-23
references.pmid: 15498458
references.citation: Nat Rev Genet. 2007 Mar;8(3):206-16
references.pmid: 17304246
references.citation: Int J Dev Biol. 2009;53(4):459-68
references.pmid: 19247967
references.citation: Evol Dev. 2004 Nov-Dec;6(6):393-401
references.pmid: 15509221
references.citation: Development. 1999 Apr;126(7):1515-26
references.pmid: 10068644
references.citation: PLoS One. 2007 Aug 15;2(8):e741
references.pmid: 17710141
references.citation: Mol Biol Evol. 2004 Jan;21(1):36-44
references.pmid: 12949132
references.citation: Biochem Genet. 1982 Aug;20(7-8):747-62
references.pmid: 6814420
references.citation: Genes Dev. 1991 May;5(5):855-67
references.pmid: 1851122
references.citation: Am J Hum Genet. 2001 Apr;68(4):978-89
references.pmid: 11254454
references.citation: Genetics. 2002 Jan;160(1):247-56
references.pmid: 11805060
references.citation: PLoS Genet. 2009 Nov;5(11):e1000709
references.pmid: 19893611
references.citation: Bioessays. 2009 Jul;31(7):727-35
references.pmid: 19492354
references.citation: Bioinformatics. 2003 Dec 12;19(18):2496-7
references.pmid: 14668244
references.citation: Mol Cell Biol. 1992 Nov;12(11):4919-29
references.pmid: 1406669
references.citation: Genes Dev. 1990 Jul;4(7):1224-39
references.pmid: 1976571
references.citation: Evol Dev. 2001 Nov-Dec;3(6):397-407
references.pmid: 11806635
references.citation: Nature. 2008 Mar 6;452(7183):112-5
references.pmid: 18322535
references.citation: Genome Biol Evol. 2011;3:114-28
references.pmid: 21173424
references.citation: Trends Genet. 2004 Jul;20(7):305-13
references.pmid: 15219395
references.citation: Mol Cell Biol. 1993 Sep;13(9):5549-59
references.pmid: 8355700
references.citation: Bioessays. 1990 Mar;12(3):109-13
references.pmid: 2108665
references.citation: Nucleic Acids Res. 2004 Jul 1;32(Web Server issue):W33-6
references.pmid: 15215344
references.citation: Mol Biol Evol. 2004 Feb;21(2):348-63
references.pmid: 14660693
references.citation: Nat Rev Genet. 2007 Oct;8(10):803-13
references.pmid: 17878896
references.citation: Mol Oncol. 2008 Aug;2(2):182-90
references.pmid: 19383337
references.citation: Plant J. 2008 Oct;56(2):287-296
references.pmid: 18643973
references.citation: Brief Bioinform. 2008 Jul;9(4):326-32
references.pmid: 18436575
references.citation: Mol Biol Evol. 2005 Oct;22(10):2119-30
references.pmid: 15987874
references.citation: Nature. 2005 Oct 20;437(7062):1149-52
references.pmid: 16237443
references.citation: Genes Dev. 1989 Mar;3(3):384-98
references.pmid: 2498165
references.citation: Mol Biol Evol. 1991 Nov;8(6):892-6
references.pmid: 1775070
references.citation: Development. 1995 Feb;121(2):453-62
references.pmid: 7768186
references.citation: Nature. 1989 Sep 28;341(6240):340-3
references.pmid: 2571934
references.citation: Evol Dev. 2006 Jan-Feb;8(1):6-15
references.pmid: 16409378
references.citation: Mol Biol Evol. 2003 May;20(5):792-9
references.pmid: 12679536
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):18040-5
references.pmid: 20921393
references.citation: Nucleic Acids Res. 1996 Jan 1;24(1):238-41
references.pmid: 8594589
references.citation: Nucleic Acids Res. 1990 Oct 25;18(20):6097-100
references.pmid: 2172928
references.citation: Mol Biol Evol. 1995 Nov;12(6):1002-11
references.pmid: 8524036
references.citation: Nature. 1993 Oct 7;365(6446):548-50
references.pmid: 8413609
references.citation: Yeast. 2002 Jan 30;19(2):99-114
references.pmid: 11788965
references.citation: J Biochem Biophys Methods. 1995 Feb;30(1):85-9
references.pmid: 7608473
references.citation: BMC Evol Biol. 2004 Oct 28;4:42
references.pmid: 15511291
references.citation: Development. 1998 Mar;125(5):949-58
references.pmid: 9449677
references.citation: Cell. 1987 Sep 11;50(6):963-74
references.pmid: 2887293
references.citation: Philos Trans R Soc Lond B Biol Sci. 2010 Aug 27;365(1552):2571-80
references.pmid: 20643747
references.citation: Development. 2010 Jan;137(1):5-13
references.pmid: 20023155
references.citation: Mol Biol Evol. 1994 Mar;11(2):287-304
references.pmid: 8170369
references.citation: Methods Enzymol. 1993;224:525-41
references.pmid: 8264408
references.citation: Gene. 1992 Jan 15;110(2):225-8
references.pmid: 1537559
references.citation: BMC Syst Biol. 2010 Nov 08;4:150
references.pmid: 21059252
references.citation: Biol Lett. 2008 Aug 23;4(4):438-41
references.pmid: 18505714
references.citation: Proc Biol Sci. 1995 Aug 22;261(1361):203-7
references.pmid: 7568273
references.citation: Trends Genet. 2007 Jun;23(6):273-7
references.pmid: 17418442
references.citation: Biochimie. 2008 Aug;90(8):1149-71
references.pmid: 18355457
references.citation: Nature. 2007 Aug 2;448(7153):587-90
references.pmid: 17632547
references.citation: Nucleic Acids Res. 1994 Nov 11;22(22):4673-80
references.pmid: 7984417
references.citation: Genetics. 1989 Nov;123(3):585-95
references.pmid: 2513255
references.citation: DNA Cell Biol. 2010 Sep;29(9):499-508
references.pmid: 20438356
references.citation: Nature. 1982 Sep 9;299(5879):111-7
references.pmid: 7110332
references.citation: PLoS Biol. 2005 Apr;3(4):e93
references.pmid: 15757364
references.citation: Genetics. 1993 Mar;133(3):693-709
references.pmid: 8454210
references.citation: Am J Hum Genet. 2003 Nov;73(5):1162-9
references.pmid: 14574645