April 2014
Volume 55, Issue 13
ARVO Annual Meeting Abstract  |   April 2014
Zebrafish phosphodiesterase 6: circadian subfunctionalisation of novel inhibitory subunits
Author Affiliations & Notes
  • Xesus Abalo
    Neuroscience, Uppsala Universitet, Uppsala, Sweden
  • David Lagman
    Neuroscience, Uppsala Universitet, Uppsala, Sweden
  • Dan Larhammar
    Neuroscience, Uppsala Universitet, Uppsala, Sweden
  • Footnotes
    Commercial Relationships Xesus Abalo, None; David Lagman, None; Dan Larhammar, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science April 2014, Vol.55, 3033. doi:
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      Xesus Abalo, David Lagman, Dan Larhammar; Zebrafish phosphodiesterase 6: circadian subfunctionalisation of novel inhibitory subunits. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3033.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: Hundreds of gene families expanded in the early vertebrate tetraploidizations (2R) including many gene families involved in the phototransduction cascade. The main interest of our group is to shed light on the evolution of the vertebrate visual system, focusing on the phototransduction cascade proteins. A crucial player in the cascade is phosphodiesterase 6 (PDE6) which catalyse the hydrolysis of cGMP into GMP, what leads to the closure of the photoreceptor-specific cyclic nucleotide-gated ion channel and provokes a hyperpolarisation of the photoreceptor. PDE6 consists of a catalytic dimer (heterodimer made of alpha and beta subunits in rods and homodimer made of two alpha-prime subunits in cones) and two inhibitory gamma subunits in tetrapods, with separate gamma subtypes expressed in rods and cones. In this work, we have deduced the evolutionary history of the PDE6 subunit genes in vertebrates and analyse the impact of the teleost-specific tetraploidisation (3R) on gene duplicates using zebrafish as a model.

Methods: The evolutionary analysis of the PDE6 gene family was performed using both sequence-based phylogenetic analyses and comparisons of conserved synteny. Gene expression analyses were performed by in situ hybridisation and RT-qPCR.

Results: The phylogenetic analysis of the PDE6 gene family revealed duplications of a single ancestral catalytic subunit gene in 2R, resulting in the vertebrate isoforms: pde6a, pde6b, and pde6c. The inhibitory subunit gene seems to have arisen in the vertebrate lineage and duplicated in 2R: pde6g and pde6h. These results are likely linked to the emergence of the rods in vertebrates and the capability of adaptation to nocturnal life. Remarkably, 3R generated copies only of the inhibitory subunit genes, leading zebrafish to gain two additional gamma subunits plus one due to a separate duplication event, thus five in total. Expression analysis shows expression of two paralogs in rods and two in cones with a remarkable circadian oscillation in their expression levels, and the absence of expression for the fifth paralog. These results suggest subfunctionalisation after the duplications allowing adaptation to diurnal light-dark cycles.

Conclusions: Evolution supplied vertebrates with inhibitory subunits to regulate the catalytic activity of the PDE6. Teleost fish gained extra copies for the gamma subunit after 3R that are regulated in a circadian manner.

Keywords: 648 photoreceptors • 516 evolution  

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