Abstract
Transducin is a heterotrimeric G protein that plays a critical role in phototransduction in the rod and cone photoreceptor cells of the vertebrate retina. Rods, highly sensitive cells that recover from photoactivation slowly, underlie dim-light vision, whereas cones are less sensitive, recover more quickly, and underlie bright-light vision. Transducin deactivation is a critical step in photoreceptor recovery and may underlie the functional distinction between rods and cones. Rods and cones possess distinct transducin α subunits, yet they share a common deactivation mechanism, the GTPase activating protein (GAP) complex. Here, we used codon models to examine patterns of sequence evolution in rod (GNAT1) and cone (GNAT2) α subunits. Our results indicate that purifying selection is the dominant force shaping GNAT1 and GNAT2 evolution, but that GNAT2 has additionally been subject to positive selection operating at multiple phylogenetic scales; phylogeny-wide analysis identified several sites in the GNAT2 helical domain as having substantially elevated dN/dS estimates, and branch-site analysis identified several nearby sites as targets of strong positive selection during early vertebrate history. Examination of aligned GNAT and GAP complex crystal structures revealed steric clashes between several positively selected sites and the deactivating GAP complex. This suggests that GNAT2 sequence variation could play an important role in adaptive evolution of the vertebrate visual system via effects on photoreceptor deactivation kinetics and provides an alternative perspective to previous work that focused instead on the effect of GAP complex concentration. Our findings thus further the understanding of the molecular biology, physiology, and evolution of vertebrate visual systems.
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Acknowledgments
This work was supported by a Natural Sciences and Engineering Research Council (NSERC) Discovery grant (B.S.W.C.), an NSERC graduate fellowship (C.J.W.), the Vision Science Research Fellowship Program (C.J.W.), and an NSERC Undergraduate Student Research Award (G.L.).
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Y. Gloria Lin and Cameron J. Weadick have contributed equally to this work.
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G. Lin, Y., Weadick, C.J., Santini, F. et al. Molecular Evolutionary Analysis of Vertebrate Transducins: A Role for Amino Acid Variation in Photoreceptor Deactivation. J Mol Evol 77, 231–245 (2013). https://doi.org/10.1007/s00239-013-9589-5
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DOI: https://doi.org/10.1007/s00239-013-9589-5