Molecular Evolution of Vertebrate Neurotrophins: Co-Option of the Highly Conserved Nerve Growth Factor Gene into the Advanced Snake Venom Arsenalf
Year: 2013
Type: article
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.
Source: PLoS ONE
Institutions: Universidade do Porto, Centro Interdisciplinar de Investigação Marinha e Ambiental, The University of Queensland, Institute for Molecular Bioscience, Bangor University, Liverpool School of Tropical Medicine, Muséum national d'Histoire naturelle, Évolution Paris Seine, University of Karachi, International Center for Chemical and Biological Sciences, Wildlife Institute of India
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1167214205, G1578237752, G1680372705, MOLECULAR EVOLUTION OF VENOM: A COMPARATIVE APPROACH TO ASSESS EVOLUTION OF VENOM ENCODING GENES ACROSS TERRESTRIAL AND AQUATIC ORGANISMS, G3182596604, G3605313435, G3854150261, A novel approach for controlling insect vectors of human disease, G5888032724, G5943698181, Projecto Estratégico - LA 15 - 2013-2014, G6273007362, G6576766485, Origin, evolution and functional diversification of a chemical arsenal: venom in bony and cartilaginous fish, G8868700560, G8952488736, G948844139
OpenAlex ID: W1982514387