Identification and analysis of internal promoters in Caenorhabditis elegans operons.
The current Caenorhabditis elegans genomic annotation has many genes organized in operons. Using directionally stitched promoterGFP methodology, we have conducted the largest survey to date on the regulatory regions of annotated C. elegans operons and identified 65, over 25% of those studied, with internal promoters. We have termed these operons "hybrid operons." GFP expression patterns driven from internal promoters differ in tissue specificity from expression of operon promoters, and serial analysis of gene expression data reveals that there is a lack of expression correlation between genes in many hybrid operons. The average length of intergenic regions with putative promoter activity in hybrid operons is larger than previous estimates for operons as a whole. Genes with internal promoters are more commonly involved in gene duplications and have a significantly lower incidence of alternative splicing than genes without internal promoters, although we have observed almost all trans-splicing patterns in these two distinct groups. Finally, internal promoter constructs are able to rescue lethal knockout phenotypes, demonstrating their necessity in gene regulation and survival. Our work suggests that hybrid operons are common in the C. elegans genome and that internal promoters influence not only gene organization and expression but also operon evolution.
Huang
Peiming
P
Genome Sciences Centre, BC Cancer Agency, Vancouver, British Columbia V5Z 1L3, Canada.
Pleasance
Erin D
ED
Maydan
Jason S
JS
Hunt-Newbury
Rebecca
R
O'Neil
Nigel J
NJ
Mah
Allan
A
Baillie
David L
DL
Marra
Marco A
MA
Moerman
Donald G
DG
Jones
Steven J M
SJ
D017398:Alternative Splicing; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000235:genetics*; D019143:Evolution, Molecular; D020440:Gene Duplication; D020869:Gene Expression Profiling; D017238:Genes, Helminth; D017930:Genes, Reporter; D049751:Genome, Helminth; D023281:Genomics; D049452:Green Fluorescent Proteins / Q000235:genetics; D009876:Operon; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics
D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins
J Biol Chem. 1995 Sep 15;270(37):22066-75
7665629
Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):5768-72
7597027
Genetics. 1996 Aug;143(4):1699-711
8844157
Mol Cell Biol. 1997 Mar;17(3):1714-21
9032298
RNA. 2005 Feb;11(2):128-38
15659355
Mol Biol Evol. 2005 Mar;22(3):767-75
15574806
RNA. 2007 Apr;13(4):511-20
17283210
Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9753-7
17535930
WormBook. 2005;:1-9
18050426
Trends Genet. 1995 Apr;11(4):132-6
7732590
Science. 2000 Mar 24;287(5461):2204-15
10731134
Genetics. 2000 Apr;154(4):1735-46
10747066
Mol Cell Biol. 2000 Sep;20(18):6659-67
10958663
Science. 2000 Nov 10;290(5494):1151-5
11073452
Nucleic Acids Res. 2001 Jan 1;29(1):82-6
11125056
RNA. 2001 Feb;7(2):176-81
11233975
Trends Genet. 2001 Dec;17(12):678-80
11718904
Nat Biotechnol. 2002 May;20(5):508-12
11981567
Nature. 2002 Jun 20;417(6891):851-4
12075352
Nat Rev Genet. 2003 Feb;4(2):112-20
12560808
Genome Res. 2003 Feb;13(2):238-43
12566401
Trends Genet. 2003 Mar;19(3):124-8
12615003
Genome Res. 2003 Jun;13(6A):1203-15
12743019
Genes Dev. 2003 Sep 1;17(17):2123-37
12952888
Genome Res. 2004 Jan;14(1):62-6
14707170
Proc Natl Acad Sci U S A. 2004 Feb 10;101(6):1650-5
14757812
Genes Chromosomes Cancer. 2004 Aug;40(4):285-97
15188451
Cold Spring Harb Symp Quant Biol. 2003;68:159-69
15338614
Genome Res. 2004 Oct;14(10B):2169-75
15489340
J Biol Chem. 1983 Jul 10;258(13):7890-3
6305961
Cell. 1986 Nov 21;47(4):517-25
3779835
Nucleic Acids Res. 1987 Sep 25;15(18):7357-68
3658696
Proc Natl Acad Sci U S A. 1989 Nov;86(22):8640-4
2813415
Nature. 1991 Sep 5;353(6339):90-4
1652694
Development. 1991 Oct;113(2):399-408
1782857
Cell. 1993 May 7;73(3):521-32
8098272
Science. 1994 Feb 11;263(5148):802-5
8303295
Development. 1994 Mar;120(3):505-14
8162851
Nature. 1994 Nov 17;372(6503):270-2
7969472
Genome Res. 1997 May;7(5):541-50
9149949
Development. 1997 May;124(9):1699-709
9165118
Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):8249-54
9223347
Genome Res. 1997 Oct;7(10):986-95
9331369
Mol Gen Genet. 1998 Nov;260(2-3):300-8
9862485
Nucleic Acids Res. 1999 Feb 1;27(3):854-8
9889283
J Mol Evol. 1999 May;48(5):555-64
10198121
Nucleic Acids Res. 1999 Sep 1;27(17):3424-32
10446229
J Mol Biol. 1961 Jun;3:318-56
13718526
J Mol Biol. 2004 Nov 19;344(2):409-17
15522294
Biotechnol Prog. 2004 Nov-Dec;20(6):1634-40
15575693
Brief Funct Genomic Proteomic. 2004 Nov;3(3):199-211
15642184
Science. 1995 Oct 20;270(5235):484-7
7570003