The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

Freek J Vonk, Nicholas R Casewell, Christiaan V Henkel, Alysha Heimberg, Hans J Jansen, Ryan J R McCleary, Harald M E Kerkkamp, Rutger A Vos, Isabel Guerreiro, Juan J Calvete, Wolfgang Wuster, Anthony E Woods, Jessica M Logan, Robert A Harrison, Todd A Castoe, A P Jason de Koning, David D Pollock, Mark Yandell, Diego Calderon, Camila Renjifo & 16 others Rachel B Currier, David Salgado, Davinia Pla, Libia Sanz, Asad S Hyder, Jose M C Ribeiro, Jan W Arntzen, Guido E E J M van den Thillart, Marten Boetzer, Walter Pirovano, Ron P Dirks, Herman P Spaink, Denis Duboule, Edwina McGlinn, Rikard Manjunatha Kini, Michael K Richardson

Research output: Contribution to journalArticleResearchpeer-review

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.
Original languageEnglish
Pages (from-to)20651 - 20656
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume110
Issue number51
DOIs
Publication statusPublished - 2013

Cite this

Vonk, F. J., Casewell, N. R., Henkel, C. V., Heimberg, A., Jansen, H. J., McCleary, R. J. R., ... Richardson, M. K. (2013). The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. Proceedings of the National Academy of Sciences, 110(51), 20651 - 20656. https://doi.org/10.1073/pnas.1314702110
Vonk, Freek J ; Casewell, Nicholas R ; Henkel, Christiaan V ; Heimberg, Alysha ; Jansen, Hans J ; McCleary, Ryan J R ; Kerkkamp, Harald M E ; Vos, Rutger A ; Guerreiro, Isabel ; Calvete, Juan J ; Wuster, Wolfgang ; Woods, Anthony E ; Logan, Jessica M ; Harrison, Robert A ; Castoe, Todd A ; de Koning, A P Jason ; Pollock, David D ; Yandell, Mark ; Calderon, Diego ; Renjifo, Camila ; Currier, Rachel B ; Salgado, David ; Pla, Davinia ; Sanz, Libia ; Hyder, Asad S ; Ribeiro, Jose M C ; Arntzen, Jan W ; van den Thillart, Guido E E J M ; Boetzer, Marten ; Pirovano, Walter ; Dirks, Ron P ; Spaink, Herman P ; Duboule, Denis ; McGlinn, Edwina ; Kini, Rikard Manjunatha ; Richardson, Michael K. / The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. In: Proceedings of the National Academy of Sciences. 2013 ; Vol. 110, No. 51. pp. 20651 - 20656.
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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.",
author = "Vonk, {Freek J} and Casewell, {Nicholas R} and Henkel, {Christiaan V} and Alysha Heimberg and Jansen, {Hans J} and McCleary, {Ryan J R} and Kerkkamp, {Harald M E} and Vos, {Rutger A} and Isabel Guerreiro and Calvete, {Juan J} and Wolfgang Wuster and Woods, {Anthony E} and Logan, {Jessica M} and Harrison, {Robert A} and Castoe, {Todd A} and {de Koning}, {A P Jason} and Pollock, {David D} and Mark Yandell and Diego Calderon and Camila Renjifo and Currier, {Rachel B} and David Salgado and Davinia Pla and Libia Sanz and Hyder, {Asad S} and Ribeiro, {Jose M C} and Arntzen, {Jan W} and {van den Thillart}, {Guido E E J M} and Marten Boetzer and Walter Pirovano and Dirks, {Ron P} and Spaink, {Herman P} and Denis Duboule and Edwina McGlinn and Kini, {Rikard Manjunatha} and Richardson, {Michael K}",
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Vonk, FJ, Casewell, NR, Henkel, CV, Heimberg, A, Jansen, HJ, McCleary, RJR, Kerkkamp, HME, Vos, RA, Guerreiro, I, Calvete, JJ, Wuster, W, Woods, AE, Logan, JM, Harrison, RA, Castoe, TA, de Koning, APJ, Pollock, DD, Yandell, M, Calderon, D, Renjifo, C, Currier, RB, Salgado, D, Pla, D, Sanz, L, Hyder, AS, Ribeiro, JMC, Arntzen, JW, van den Thillart, GEEJM, Boetzer, M, Pirovano, W, Dirks, RP, Spaink, HP, Duboule, D, McGlinn, E, Kini, RM & Richardson, MK 2013, 'The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system' Proceedings of the National Academy of Sciences, vol. 110, no. 51, pp. 20651 - 20656. https://doi.org/10.1073/pnas.1314702110

The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system. / Vonk, Freek J; Casewell, Nicholas R; Henkel, Christiaan V; Heimberg, Alysha; Jansen, Hans J; McCleary, Ryan J R; Kerkkamp, Harald M E; Vos, Rutger A; Guerreiro, Isabel; Calvete, Juan J; Wuster, Wolfgang; Woods, Anthony E; Logan, Jessica M; Harrison, Robert A; Castoe, Todd A; de Koning, A P Jason; Pollock, David D; Yandell, Mark; Calderon, Diego; Renjifo, Camila; Currier, Rachel B; Salgado, David; Pla, Davinia; Sanz, Libia; Hyder, Asad S; Ribeiro, Jose M C; Arntzen, Jan W; van den Thillart, Guido E E J M; Boetzer, Marten; Pirovano, Walter; Dirks, Ron P; Spaink, Herman P; Duboule, Denis; McGlinn, Edwina; Kini, Rikard Manjunatha; Richardson, Michael K.

In: Proceedings of the National Academy of Sciences, Vol. 110, No. 51, 2013, p. 20651 - 20656.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The king cobra genome reveals dynamic gene evolution and adaptation in the snake venom system

AU - Vonk, Freek J

AU - Casewell, Nicholas R

AU - Henkel, Christiaan V

AU - Heimberg, Alysha

AU - Jansen, Hans J

AU - McCleary, Ryan J R

AU - Kerkkamp, Harald M E

AU - Vos, Rutger A

AU - Guerreiro, Isabel

AU - Calvete, Juan J

AU - Wuster, Wolfgang

AU - Woods, Anthony E

AU - Logan, Jessica M

AU - Harrison, Robert A

AU - Castoe, Todd A

AU - de Koning, A P Jason

AU - Pollock, David D

AU - Yandell, Mark

AU - Calderon, Diego

AU - Renjifo, Camila

AU - Currier, Rachel B

AU - Salgado, David

AU - Pla, Davinia

AU - Sanz, Libia

AU - Hyder, Asad S

AU - Ribeiro, Jose M C

AU - Arntzen, Jan W

AU - van den Thillart, Guido E E J M

AU - Boetzer, Marten

AU - Pirovano, Walter

AU - Dirks, Ron P

AU - Spaink, Herman P

AU - Duboule, Denis

AU - McGlinn, Edwina

AU - Kini, Rikard Manjunatha

AU - Richardson, Michael K

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

UR - http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870661/pdf/pnas.201314702.pdf

U2 - 10.1073/pnas.1314702110

DO - 10.1073/pnas.1314702110

M3 - Article

VL - 110

SP - 20651

EP - 20656

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 0027-8424

IS - 51

ER -