PMID- 24312363
OWN - NLM
STAT- MEDLINE
DCOM- 20140805
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 11
DP  - 2013
TI  - Molecular evolution of vertebrate neurotrophins: co-option of the highly 
      conserved nerve growth factor gene into the advanced snake venom arsenalf.
PG  - e81827
LID - 10.1371/journal.pone.0081827 [doi]
LID - e81827
AB  - 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 beta-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.
FAU - Sunagar, Kartik
AU  - Sunagar K
AD  - CIMAR/CIIMAR, Centro Interdisciplinar de Investigacao Marinha e Ambiental, 
      Universidade do Porto, Porto, Portugal ; Departamento de Biologia, Faculdade de 
      Ciencias, Universidade do Porto, Porto, Portugal.
FAU - Fry, Bryan Grieg
AU  - Fry BG
FAU - Jackson, Timothy N W
AU  - Jackson TN
FAU - Casewell, Nicholas R
AU  - Casewell NR
FAU - Undheim, Eivind A B
AU  - Undheim EA
FAU - Vidal, Nicolas
AU  - Vidal N
FAU - Ali, Syed A
AU  - Ali SA
FAU - King, Glenn F
AU  - King GF
FAU - Vasudevan, Karthikeyan
AU  - Vasudevan K
FAU - Vasconcelos, Vitor
AU  - Vasconcelos V
FAU - Antunes, Agostinho
AU  - Antunes A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131129
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Snake Venoms)
RN  - 9061-61-4 (Nerve Growth Factor)
SB  - IM
MH  - Animals
MH  - Bayes Theorem
MH  - Elapidae
MH  - *Evolution, Molecular
MH  - Likelihood Functions
MH  - Nerve Growth Factor/*genetics
MH  - Nerve Growth Factors/*genetics
MH  - Phylogeny
MH  - Snake Venoms/*genetics
PMC - PMC3843689
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/12/07 06:00
MHDA- 2014/08/06 06:00
PMCR- 2013/11/29
CRDT- 2013/12/07 06:00
PHST- 2013/07/08 00:00 [received]
PHST- 2013/10/17 00:00 [accepted]
PHST- 2013/12/07 06:00 [entrez]
PHST- 2013/12/07 06:00 [pubmed]
PHST- 2014/08/06 06:00 [medline]
PHST- 2013/11/29 00:00 [pmc-release]
AID - PONE-D-13-28174 [pii]
AID - 10.1371/journal.pone.0081827 [doi]
PST - epublish
SO  - PLoS One. 2013 Nov 29;8(11):e81827. doi: 10.1371/journal.pone.0081827. 
      eCollection 2013.