title: The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system.
abstract: Snakes are limbless predators, and many species use venom to help overpower relatively large, agile prey. Snake venoms are complex protein mixtures encoded by several multilocus gene families that function synergistically to cause incapacitation. To examine venom evolution, we sequenced and interrogated the genome of a venomous snake, the king cobra (Ophiophagus hannah), and compared it, together with our unique transcriptome, microRNA, and proteome datasets from this species, with data from other vertebrates. In contrast to the platypus, the only other venomous vertebrate with a sequenced genome, we find that snake toxin genes evolve through several distinct co-option mechanisms and exhibit surprisingly variable levels of gene duplication and directional selection that correlate with their functional importance in prey capture. The enigmatic accessory venom gland shows a very different pattern of toxin gene expression from the main venom gland and seems to have recruited toxin-like lectin genes repeatedly for new nontoxic functions. In addition, tissue-specific microRNA analyses suggested the co-option of core genetic regulatory components of the venom secretory system from a pancreatic origin. Although the king cobra is limbless, we recovered coding sequences for all Hox genes involved in amniote limb development, with the exception of Hoxd12. Our results provide a unique view of the origin and evolution of snake venom and reveal multiple genome-level adaptive responses to natural selection in this complex biological weapon system. More generally, they provide insight into mechanisms of protein evolution under strong selection.
authors.affiliation: Naturalis Biodiversity Center, 2333 CR, Leiden, The Netherlands.
authors.forename: Freek J
authors.initials: FJ
authors.lastname: Vonk
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Casewell
authors.forename: Christiaan V
authors.initials: CV
authors.lastname: Henkel
authors.forename: Alysha M
authors.initials: AM
authors.lastname: Heimberg
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Jansen
authors.forename: Ryan J R
authors.initials: RJ
authors.lastname: McCleary
authors.forename: Harald M E
authors.initials: HM
authors.lastname: Kerkkamp
authors.forename: Rutger A
authors.initials: RA
authors.lastname: Vos
authors.forename: Isabel
authors.initials: I
authors.lastname: Guerreiro
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calvete
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wüster
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Woods
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Logan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Harrison
authors.forename: Todd A
authors.initials: TA
authors.lastname: Castoe
authors.forename: A P Jason
authors.initials: AP
authors.lastname: de Koning
authors.forename: David D
authors.initials: DD
authors.lastname: Pollock
authors.forename: Mark
authors.initials: M
authors.lastname: Yandell
authors.forename: Diego
authors.initials: D
authors.lastname: Calderon
authors.forename: Camila
authors.initials: C
authors.lastname: Renjifo
authors.forename: Rachel B
authors.initials: RB
authors.lastname: Currier
authors.forename: David
authors.initials: D
authors.lastname: Salgado
authors.forename: Davinia
authors.initials: D
authors.lastname: Pla
authors.forename: Libia
authors.initials: L
authors.lastname: Sanz
authors.forename: Asad S
authors.initials: AS
authors.lastname: Hyder
authors.forename: José M C
authors.initials: JM
authors.lastname: Ribeiro
authors.forename: Jan W
authors.initials: JW
authors.lastname: Arntzen
authors.forename: Guido E E J M
authors.initials: GE
authors.lastname: van den Thillart
authors.forename: Marten
authors.initials: M
authors.lastname: Boetzer
authors.forename: Walter
authors.initials: W
authors.lastname: Pirovano
authors.forename: Ron P
authors.initials: RP
authors.lastname: Dirks
authors.forename: Herman P
authors.initials: HP
authors.lastname: Spaink
authors.forename: Denis
authors.initials: D
authors.lastname: Duboule
authors.forename: Edwina
authors.initials: E
authors.lastname: McGlinn
authors.forename: R Manjunatha
authors.initials: RM
authors.lastname: Kini
authors.forename: Michael K
authors.initials: MK
authors.lastname: Richardson
mesh_terms: D000220:Adaptation, Biological / Q000502:physiology*; D000818:Animals; D004546:Elapid Venoms / Q000235:genetics / Q000378:metabolism; D017815:Elapidae / Q000235:genetics / Q000378:metabolism; D019143:Evolution, Molecular; D005088:Exocrine Glands / Q000378:metabolism; D016678:Genome / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome / Q000502:physiology*
chemical_list: D004546:Elapid Venoms; D035683:MicroRNAs
keywords: genomics; phylogenetics; serpentes