title: Squeezers and leaf-cutters: differential diversification and degeneration of the venom system in toxicoferan reptiles.
abstract: Although it has been established that all toxicoferan squamates share a common venomous ancestor, it has remained unclear whether the maxillary and mandibular venom glands are evolving on separate gene expression trajectories or if they remain under shared genetic control. We show that identical transcripts are simultaneously expressed not only in the mandibular and maxillary glands, but also in the enigmatic snake rictal gland. Toxin molecular frameworks recovered in this study were three-finger toxin (3FTx), CRiSP, crotamine (beta-defensin), cobra venom factor, cystatin, epididymal secretory protein, kunitz, L-amino acid oxidase, lectin, renin aspartate protease, veficolin, and vespryn. We also discovered a novel low-molecular weight disulfide bridged peptide class in pythonid snake glands. In the iguanian lizards, the most highly expressed are potentially antimicrobial in nature (crotamine (beta-defensin) and cystatin), with crotamine (beta-defensin) also the most diverse. However, a number of proteins characterized from anguimorph lizards and caenophidian snakes with hemotoxic or neurotoxic activities were recruited in the common toxicoferan ancestor and remain expressed, albeit in low levels, even in the iguanian lizards. In contrast, the henophidian snakes express 3FTx and lectin toxins as the dominant transcripts. Even in the constricting pythonid and boid snakes, where the glands are predominantly mucous-secreting, low-levels of toxin transcripts can be detected. Venom thus appears to play little role in feeding behavior of most iguanian lizards or the powerful constricting snakes, and the low levels of expression argue against a defensive role. However, clearly the incipient or secondarily atrophied venom systems of these taxa may be a source of novel compounds useful in drug design and discovery.
authors.affiliation: Venom Evolution Laboratory, School of Biological Sciences, University of Queensland, St. Lucia, Queensland, Australia. bgfry@uq.edu.au
authors.forename: Bryan G
authors.initials: BG
authors.lastname: Fry
authors.forename: Eivind A B
authors.initials: EA
authors.lastname: Undheim
authors.forename: Syed A
authors.initials: SA
authors.lastname: Ali
authors.forename: Timothy N W
authors.initials: TN
authors.lastname: Jackson
authors.forename: Jordan
authors.initials: J
authors.lastname: Debono
authors.forename: Holger
authors.initials: H
authors.lastname: Scheib
authors.forename: Tim
authors.initials: T
authors.lastname: Ruder
authors.forename: David
authors.initials: D
authors.lastname: Morgenstern
authors.forename: Luke
authors.initials: L
authors.lastname: Cadwallader
authors.forename: Darryl
authors.initials: D
authors.lastname: Whitehead
authors.forename: Rob
authors.initials: R
authors.lastname: Nabuurs
authors.forename: Louise
authors.initials: L
authors.lastname: van der Weerd
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vidal
authors.forename: Kim
authors.initials: K
authors.lastname: Roelants
authors.forename: Iwan
authors.initials: I
authors.lastname: Hendrikx
authors.forename: Sandy Pineda
authors.initials: SP
authors.lastname: Gonzalez
authors.forename: Ivan
authors.initials: I
authors.lastname: Koludarov
authors.forename: Alun
authors.initials: A
authors.lastname: Jones
authors.forename: Glenn F
authors.initials: GF
authors.lastname: King
authors.forename: Agostinho
authors.initials: A
authors.lastname: Antunes
authors.forename: Kartik
authors.initials: K
authors.lastname: Sunagar
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D008116:Lizards / Q000235:genetics*; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D012911:Snakes / Q000235:genetics*; D059467:Transcriptome; D014688:Venoms / Q000737:chemistry / Q000235:genetics*
chemical_list: D014688:Venoms
references.citation: J Evol Biol. 2009 Jun;22(6):1308-16
references.pmid: 19490385
references.citation: Mol Cell Proteomics. 2008 Feb;7(2):215-46
references.pmid: 17855442
references.citation: Mol Cell Proteomics. 2010 Nov;9(11):2369-90
references.pmid: 20631207
references.citation: Bioinformatics. 2005 Mar 1;21(5):676-9
references.pmid: 15509596
references.citation: Curr Pharm Des. 2007;13(28):2872-86
references.pmid: 17979732
references.citation: Mol Biol Evol. 2012 Aug;29(8):2019-29
references.pmid: 22337864
references.citation: Mol Biol Evol. 1994 Sep;11(5):725-36
references.pmid: 7968486
references.citation: J Mol Evol. 2003 Oct;57(4):446-52
references.pmid: 14708577
references.citation: Syst Biol. 2004 Oct;53(5):735-57
references.pmid: 15545252
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7799-806
references.pmid: 9223266
references.citation: Int J Plant Genomics. 2008;2008:619832
references.pmid: 18483572
references.citation: Genetics. 1998 Mar;148(3):929-36
references.pmid: 9539414
references.citation: Nucleic Acids Res. 2007 Jul;35(Web Server issue):W506-11
references.pmid: 17586822
references.citation: Nature. 2006 Feb 2;439(7076):584-8
references.pmid: 16292255
references.citation: Nat Protoc. 2009;4(3):363-71
references.pmid: 19247286
references.citation: Annu Rev Genomics Hum Genet. 2009;10:483-511
references.pmid: 19640225
references.citation: Genome Res. 2005 Mar;15(3):403-20
references.pmid: 15741511
references.citation: J Mol Graph. 1996 Feb;14(1):33-8, 27-8
references.pmid: 8744570
references.citation: Gene. 2000 Dec 30;261(1):43-52
references.pmid: 11164036
references.citation: Mol Biol Evol. 2004 May;21(5):870-83
references.pmid: 15014162
references.citation: Electrophoresis. 1997 Dec;18(15):2714-23
references.pmid: 9504803
references.citation: Bioinformatics. 2011 Apr 1;27(7):919-24
references.pmid: 21335611
references.citation: Mol Biol Evol. 2011 Sep;28(9):2637-49
references.pmid: 21478373
references.citation: J Mol Evol. 2012 Dec;75(5-6):168-83
references.pmid: 23160567
references.citation: Mol Biol Evol. 2010 May;27(5):1025-34
references.pmid: 20018978
references.citation: Mol Biol Evol. 2008 Nov;25(11):2391-407
references.pmid: 18701431
references.citation: Nucleic Acids Res. 2008 Jun;36(10):3420-35
references.pmid: 18445632
references.citation: Bioinformatics. 2010 Oct 1;26(19):2455-7
references.pmid: 20671151
references.citation: J Mol Evol. 2006 May;62(5):630-44
references.pmid: 16612539
references.citation: J Virol. 2005 May;79(10):6523-7
references.pmid: 15858036
references.citation: Mol Biol Evol. 2007 Aug;24(8):1586-91
references.pmid: 17483113
references.citation: Mol Biol Evol. 2005 May;22(5):1208-22
references.pmid: 15703242
references.citation: Gene. 2012 Mar 15;496(1):1-7
references.pmid: 22285376
references.citation: Toxicon. 2012 Jun 1;59(7-8):696-708
references.pmid: 22465490
references.citation: Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):5964-8
references.pmid: 8327468
references.citation: J Mol Evol. 2004 Feb;58(2):145-53
references.pmid: 15042334
references.citation: Mol Biol Evol. 2006 Oct;23(10):1891-901
references.pmid: 16818476
references.citation: J Mol Biol. 2001 Mar 16;307(1):447-63
references.pmid: 11243830
references.citation: Mol Biol Evol. 2011 Nov;28(11):3033-43
references.pmid: 21670087
references.citation: Bioinformatics. 2005 May 1;21(9):2101-3
references.pmid: 15647294
references.citation: J Mol Evol. 2004 Jul;59(1):121-32
references.pmid: 15383915
references.citation: Mol Biol Evol. 2010 Feb;27(2):395-407
references.pmid: 19837656
references.citation: Biochemistry. 2002 Sep 24;41(38):11331-7
references.pmid: 12234174
references.citation: Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):754-9
references.pmid: 9892706
references.citation: Biochimie. 2008 Jun;90(6):868-77
references.pmid: 18343233
references.citation: Mol Cell Proteomics. 2013 Mar;12(3):651-63
references.pmid: 23242553
references.citation: Syst Biol. 2012 May;61(3):539-42
references.pmid: 22357727
references.citation: Int J Pept Res Ther. 2009;15(1):43
references.pmid: 32214926
references.citation: Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10037-41
references.pmid: 11517324
references.citation: Mol Biol Evol. 1998 May;15(5):568-73
references.pmid: 9580986
references.citation: Bioinformatics. 2005 Sep 15;21(18):3674-6
references.pmid: 16081474
references.citation: Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):6820-3
references.pmid: 10359796
references.citation: J Biol Chem. 2005 Apr 1;280(13):13137-47
references.pmid: 15668253
references.citation: Mol Biol Evol. 2009 Mar;26(3):547-66
references.pmid: 19042943
references.citation: Bioinformatics. 2003 Aug 12;19(12):1572-4
references.pmid: 12912839
references.citation: Emerg Med Australas. 2004 Oct-Dec;16(5-6):459-64
references.pmid: 15537410
references.citation: J Innate Immun. 2012;4(4):337-48
references.pmid: 22441423
references.citation: J Mol Evol. 2003 Jul;57(1):110-29
references.pmid: 12962311
references.citation: Nucleic Acids Res. 1997 Sep 1;25(17):3389-402
references.pmid: 9254694
references.citation: Mol Biol Evol. 2012 Jul;29(7):1807-22
references.pmid: 22319140
references.citation: Comp Biochem Physiol A Mol Integr Physiol. 2011 Jul;159(3):313-21
references.pmid: 21466856
references.citation: Evolution. 2012 Jan;66(1):163-78
references.pmid: 22220872
references.citation: Mol Genet Metab. 2006 Jan;87(1):8-21
references.pmid: 16275036
references.citation: C R Biol. 2005 Oct-Nov;328(10-11):1000-8
references.pmid: 16286089
references.citation: Eur J Biochem. 2002 Jun;269(11):2708-15
references.pmid: 12047379
references.citation: Biochemistry. 2005 Aug 2;44(30):10145-52
references.pmid: 16042391
references.citation: J Mol Evol. 2002 Mar;54(3):396-402
references.pmid: 11847565