4.8 Article

Ionotropic Receptors as a Driving Force behind Human Synapse Establishment

Journal

MOLECULAR BIOLOGY AND EVOLUTION
Volume 38, Issue 3, Pages 735-744

Publisher

OXFORD UNIV PRESS
DOI: 10.1093/molbev/msaa252

Keywords

neurotransmission; synapse evolution; systems biology; synapse network; ionotropic receptor

Funding

  1. governmental Brazilian agency Coordination for the Improvement of Higher Education Personnel (CAPES-Portuguese: Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)
  2. National Council of Technological and Scientific Development (CNPq) [308258/2018-5]
  3. PROPESQ-UFRN

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This study investigated the origin of nervous systems and the evolution of neurotransmission gene networks. It found a massive emergence of neuroexclusive genes, particularly ionotropic receptors, in the Human-Cnidaria common ancestor, which were crucial to the evolution of synapses. Additionally, vertebrates showed a higher abundance of synaptic proteins, indicating an increased complexity in their synaptic networks.
The origin of nervous systems is a main theme in biology and its mechanisms are largely underlied by synaptic neurotransmission. One problem to explain synapse establishment is that synaptic orthologs are present in multiple aneural organisms. We questioned how the interactions among these elements evolved and to what extent it relates to our understanding of the nervous systems complexity. We identified the human neurotransmission gene network based on genes present in GABAergic, glutamatergic, serotonergic, dopaminergic, and cholinergic systems. The network comprises 321 human genes, 83 of which act exclusively in the nervous system. We reconstructed the evolutionary scenario of synapse emergence by looking for synaptic orthologs in 476 eukaryotes. The Human-Cnidaria common ancestor displayed a massive emergence of neuroexclusive genes, mainly ionotropic receptors, which might have been crucial to the evolution of synapses. Very few synaptic genes had their origin after the Human-Cnidaria common ancestor. We also identified a higher abundance of synaptic proteins in vertebrates, which suggests an increase in the synaptic network complexity of those organisms.

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