Visual perception is initiated in the photoreceptor cells of the retina via the phototransduction system./nThis system has shown marked evolution during mammalian divergence in such complex attributes as activation time and recovery time. We have performed a molecular evolutionary analysis of proteins involved in mammalian/nphototransduction in order to unravel how the action of natural selection has been distributed throughout the/nsystem to evolve such traits. We found selective pressures to be non-randomly distributed according to both a simple protein classification scheme and a protein-interaction network representation of the signaling pathway. Proteins which are topologically central in the signaling pathway, such as the G proteins, as well as retinoid cycle chaperones and proteins involved in photoreceptor cell-type determination, were found to be more constrained in their evolution. Proteins peripheral to the pathway, such as ion channels and exchangers, as well as the retinoid cycle enzymes, have experienced a relaxation of selective pressures. Furthermore, signals of positive selection were detected in two genes: the short-wave (blue) opsin (OPN1SW) in hominids and the rod-specific Na+/Ca2+,K+ ion exchanger (SLC24A1) in rodents. The functions of the proteins involved in phototransduction and the topology of the interactions between them have imposed non-random constraints on their evolution. Thus, in shaping or conserving system-level phototransduction traits, natural selection has targeted the underlying proteins in a concerted manner.

This research was funded by grant BFU2010-19443 (subprogram BMC) awarded by Ministerio de Ciencia y Tecnología (Spain) and by the Direcció General de/nRecerca, Generalitat de Catalunya (Grup de Recerca Consolidat 2009SGR 1101). BI is supported by a FI-DGR from AGAUR, Generalitat de Catalunya (2011F1 B100275). LM acknowledges funding from the Juan de la Cierva Program of the Spanish Ministry of Science and Innovation (MICINN).