Rod and cone phototransduction: Molecular mechanism, quantitative model, and evolution of the genes Trevor Lamb Eccles Institute of Neuroscience, John Curtin School of Medical Research The Australian National University host: Peter Detwiler Abstract: The first part of this presentation will outline our current understanding of the molecular basis of the phototransduction cascade in vertebrate rod and cone photoreceptors. An overview will be given of the molecules that participate in activation, shut-off, and Ca-feedback regulation of the response to light. Activation will be described in terms of the 2‑D diffusional encounters between molecules (rhodopsin, transducin, and the phosphodiesterase PDE6). A recent discovery of considerable importance is that the PDE6 is only activated when it has two transducins bound; thus, the binding of a single transducin has negligible effect. As a result, activation of the PDE6 is substantially immune to spontaneous thermal activation of transducin. This new understanding has required the development of an updated quantitative model of phototransduction. The revised model provides new insights into: (1) the nature of the single-photon event; (2) the existence of an additional delay in the onset phase of the rod response; and (3) the recovery of rods from bright flashes, and the nature of so-called ‘dominant time constants’ of recovery. The second part of the presentation will describe how the vertebrate phototransduction cascade evolved. Around 600–700 million years ago, a simple chordate ancestor of ours possessed ciliary photoreceptor cells that probably used a single class of opsin that linked via a G‑protein cascade to cyclic nucleotide-gated ion channels, in a cascade bearing many similarities to that in present-day cones and rods. As in the case of many other vertebrate features, an event (strictly, a pair of events) of monumental significance was the occurrence of two rounds of whole genome duplication (2R WGD), that led in principle to a quadruplication of every gene. I will summarize analyses of the phylogeny (in extant species) of the genes for the proteins mediating phototransduction, and I will then describe analyses of gene synteny. The combination of these approaches provides remarkable insights into the gene duplications (and losses) that occurred, prior to 2R WGD, during 2R WGD, and subsequently, that led to the emergence of distinct isoforms for rod and cone phototransduction proteins in present-day vertebrates.
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