title: Complex expression dynamics and robustness in C. elegans insulin networks.
abstract: Gene families expand by gene duplication, and resulting paralogs diverge through mutation. Functional diversification can include neofunctionalization as well as subfunctionalization of ancestral functions. In addition, redundancy in which multiple genes fulfill overlapping functions is often maintained. Here, we use the family of 40 Caenorhabditis elegans insulins to gain insight into the balance between specificity and redundancy. The insulin/insulin-like growth factor (IIS) pathway comprises a single receptor, DAF-2. To date, no single insulin-like peptide recapitulates all DAF-2-associated phenotypes, likely due to redundancy between insulin-like genes. To provide a first-level annotation of potential patterns of redundancy, we comprehensively delineate the spatiotemporal and conditional expression of all 40 insulins in living animals. We observe extensive dynamics in expression that can explain the lack of simple patterns of pairwise redundancy. We propose a model in which gene families evolve to attain differential alliances in different tissues and in response to a range of environmental stresses.
authors.affiliation: Program in Systems Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: Ashlyn D
authors.initials: AD
authors.lastname: Ritter
authors.forename: Yuan
authors.initials: Y
authors.lastname: Shen
authors.forename: Juan
authors.initials: J
authors.lastname: Fuxman Bass
authors.forename: Sankarganesh
authors.initials: S
authors.lastname: Jeyaraj
authors.forename: Bart
authors.initials: B
authors.lastname: Deplancke
authors.forename: Arnab
authors.initials: A
authors.lastname: Mukhopadhyay
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Monica
authors.initials: M
authors.lastname: Driscoll
authors.forename: Heidi A
authors.initials: HA
authors.lastname: Tissenbaum
authors.forename: Albertha J M
authors.initials: AJ
authors.lastname: Walhout
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D007328:Insulin / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction
chemical_list: D007328:Insulin
references.citation: Genome Res. 2011 May;21(5):645-57
references.pmid: 21324878
references.citation: Cell Metab. 2009 Nov;10(5):379-91
references.pmid: 19883616
references.citation: PLoS One. 2008;3(11):e3721
references.pmid: 19005568
references.citation: Peptides. 2002 Apr;23(4):807-16
references.pmid: 11897402
references.citation: Science. 1994 Feb 11;263(5148):802-5
references.pmid: 8303295
references.citation: Appl Environ Microbiol. 2012 Apr;78(7):2075-81
references.pmid: 22286994
references.citation: Proc Natl Acad Sci U S A. 2007 Nov 27;104(48):19046-50
references.pmid: 18025456
references.citation: Science. 2012 May 4;336(6081):582-5
references.pmid: 22556251
references.citation: Nature. 2003 Jul 17;424(6946):277-83
references.pmid: 12845331
references.citation: Curr Biol. 2002 Aug 6;12(15):1317-9
references.pmid: 12176360
references.citation: Annu Rev Genet. 2011;45:1-20
references.pmid: 21721943
references.citation: Proc Natl Acad Sci U S A. 2001 Nov 20;98(24):13763-8
references.pmid: 11698650
references.citation: Development. 2011 Mar;138(6):1183-93
references.pmid: 21343369
references.citation: J Neurosci Methods. 2010 Apr 30;188(1):58-61
references.pmid: 20149821
references.citation: Aging Cell. 2012 Dec;11(6):978-85
references.pmid: 22935001
references.citation: Dev Biol. 2005 Aug 15;284(2):500-8
references.pmid: 15987632
references.citation: PLoS Genet. 2010 Feb 26;6(2):e1000857
references.pmid: 20195512
references.citation: PLoS One. 2011 Mar 22;6(3):e18086
references.pmid: 21445366
references.citation: Genetics. 2001 Mar;157(3):1217-26
references.pmid: 11238406
references.citation: Trends Neurosci. 2002 Apr;25(4):212-6
references.pmid: 11998690
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4372-6
references.pmid: 12676999
references.citation: Genome Res. 1998 Apr;8(4):348-53
references.pmid: 9548970
references.citation: Genetics. 1998 Sep;150(1):129-55
references.pmid: 9725835
references.citation: Genetics. 1998 Feb;148(2):703-17
references.pmid: 9504918
references.citation: Genome Res. 2007 Jul;17(7):1061-71
references.pmid: 17513831
references.citation: Philos Trans R Soc Lond B Biol Sci. 2011 Jan 12;366(1561):9-16
references.pmid: 21115525
references.citation: Development. 2010 Feb;137(4):671-80
references.pmid: 20110332
references.citation: Genome Res. 2008 Dec;18(12):2005-15
references.pmid: 18981266
references.citation: Nature. 2011 Dec 07;480(7376):250-3
references.pmid: 22158248
references.citation: Genetics. 1999 Apr;151(4):1531-45
references.pmid: 10101175
references.citation: Nat Rev Genet. 2004 Nov;5(11):826-37
references.pmid: 15520792
references.citation: Genome Res. 2003 Nov;13(11):2498-504
references.pmid: 14597658
references.citation: BMC Genomics. 2007 Jan 23;8:27
references.pmid: 17244357
references.citation: Cell. 2009 Jul 23;138(2):314-27
references.pmid: 19632181
references.citation: Comp Biochem Physiol B. 1990;96(4):633-7
references.pmid: 2225768
references.citation: Genes Dev. 2003 Apr 1;17(7):844-58
references.pmid: 12654727
references.citation: Genome Res. 2004 Oct;14(10B):2169-75
references.pmid: 15489340
references.citation: Genes Dev. 2001 Mar 15;15(6):672-86
references.pmid: 11274053
references.citation: Nucleic Acids Res. 1998 Apr 1;26(7):1621-7
references.pmid: 9512531
references.citation: Genes Dev. 2007 Aug 1;21(15):1882-94
references.pmid: 17652178
references.citation: Nature. 2010 Feb 18;463(7283):913-8
references.pmid: 20164922
references.citation: Cell. 2013 Mar 28;153(1):240-52
references.pmid: 23540701
references.citation: Genetics. 1997 May;146(1):227-38
references.pmid: 9136012
references.citation: PLoS One. 2011 Jan 17;6(1):e14507
references.pmid: 21264209
references.citation: Nature. 2002 Oct 24;419(6909):808-14
references.pmid: 12397350