Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf

Sunagar, Kartik, Fry, Bryan Grieg, Jackson, Timothy N. W., Casewell, Nicholas R., Undheim, Eivind A. B., Vidal, Nicolas, Ali, Syed A., King, Glenn F., Vasudevan, Karthikeyan, Vasconcelos, Vitor and Antunes, Agostinho (2013) Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf. PLoS One, 8 11: e81827.1-e81827.19. doi:10.1371/journal.pone.0081827


Author Sunagar, Kartik
Fry, Bryan Grieg
Jackson, Timothy N. W.
Casewell, Nicholas R.
Undheim, Eivind A. B.
Vidal, Nicolas
Ali, Syed A.
King, Glenn F.
Vasudevan, Karthikeyan
Vasconcelos, Vitor
Antunes, Agostinho
Title Molecular evolution of vertebrate neurotrophins: co-option of the highly conserved nerve growth factor gene into the advanced snake venom arsenalf
Journal name PLoS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-11
Sub-type Article (original research)
DOI 10.1371/journal.pone.0081827
Open Access Status DOI
Volume 8
Issue 11
Start page e81827.1
End page e81827.19
Total pages 19
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Abstract Neurotrophins are a diverse class of structurally related proteins, essential for neuronal development, survival, plasticity and regeneration. They are characterized by major family members, such as the nerve growth factors (NGF), brain-derived neurotrophic factors (BDNF) and neurotrophin-3 (NT-3), which have been demonstrated here to lack coding sequence variations and follow the regime of negative selection, highlighting their extremely important conserved role in vertebrate homeostasis. However, in stark contrast, venom NGF secreted as part of the chemical arsenal of the venomous advanced snake family Elapidae (and to a lesser extent Viperidae) have characteristics consistent with the typical accelerated molecular evolution of venom components. This includes a rapid rate of diversification under the significant influence of positive-selection, with the majority of positively-selected sites found in the secreted β-polypeptide chain (74%) and on the molecular surface of the protein (92%), while the core structural and functional residues remain highly constrained. Such focal mutagenesis generates active residues on the toxin molecular surface, which are capable of interacting with novel biological targets in prey to induce a myriad of pharmacological effects. We propose that caenophidian NGFs could participate in prey-envenoming by causing a massive release of chemical mediators from mast cells to mount inflammatory reactions and increase vascular permeability, thereby aiding the spread of other toxins and/or by acting as proapoptotic factors. Despite their presence in reptilian venom having been known for over 60 years, this is the first evidence that venom-secreted NGF follows the molecular evolutionary pattern of other venom components, and thus likely participates in prey-envenomation.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biological Sciences Publications
Institute for Molecular Bioscience - Publications
 
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