The loss of the PDE6 deactivating enzyme, RGS9, results in precocious light adaptation at low light levels

Abstract

The GTPase activating protein, RGS9-1, is vital for the deactivation and regulation of the phototransduction cascade (C. K. Chen et al., 2000; C. W. Cowan, R. N. Fariss, I. Sokal, K. Palczewski, & T. G. Wensel, 1998; W. He, C. W. Cowan, & T. G. Wensel, 1998; A. L. Lyubarsky et al., 2001). Its loss through genetic defects in humans has been linked to a slow recovery to changes in illumination (K. M. Nishiguchi et al., 2004). Such a deficit is to be expected because RGS9-1 normally speeds up the deactivation of the activated phosphodiesterase effector molecule, PDE6*, and thus accelerates the turning off of the visual response. Paradoxically, however, we find that the cone response in an observer lacking RGS9-1 is faster at lower light levels than it is in a normal observer. Though surprising, this result is nonetheless consistent with molecular models of light adaptation (e.g., E. N. Pugh, S. Nikonov, & T. D. Lamb, 1999), which predict that the excess of PDE6* resulting from the loss of RGS9-1 will shorten the visual integration time and speed up the visual response at inappropriately low light levels. The gain in speed caused by the superfluity of PDE6* at lower light levels compensates for the loss caused by its slow deactivation; thus quickening the response relative to that in the normal. As the light level is increased and the PDE6* concentration in the normal rises relative to that in the observer lacking RGS9-1, the temporal advantage of the latter is soon lost, leaving only the deficit due to delayed deactivation.

Genomic landscape of positive natural selection in Northern European populations

“…32,33 Yet another intriguing gene is RGS9 that affects vision adaptation in different light conditions. 34,35 However, lack of selection signal in individual loci in this study should not be interpreted as absence of selection, as there are several interesting regions lacking sufficient SNP coverage -including the loci of, for example, the LCT and OCA2 genes and the CYP3A region, all well-known candidates for recent natural selection. 9,36,37 In addition, the iHS and LRH tests have good power to detect selected haplotypes only in a relatively narrow frequency range, which may be the reason why some other wellestablished candidate genes, such as SLC24A5 38 and MYOA5, 9 show a lower signal below the chosen thresholds of this study.…”

The Relationship between Slow Photoresponse Recovery Rate and Temporal Resolution of Vision

“…Therefore, it is interesting to compare insights drawn from the present study to visual deficits experienced by human patients with bradyopsia. As mentioned above, bradyopsia is a congenital condition caused by mutations in the RGS9 and R9AP genes (Nishiguchi et al, 2004; Cheng et al, 2007; Hartong et al, 2007; Stockman et al, 2008; Michaelides et al, 2010), characterized by a difficulty to see low contrast moving objects, adapting to abrupt changes in ambient light intensity and photophobia, i.e. intolerance to bright light.…”

A detailed phenotypic description of autosomal dominant cone dystrophy due to a de novo mutation in the GUCY2D gene

“…The system is described in more detail elsewhere. 14,15 A flickering target of 41 of visual angle in diameter was presented in the centre of a 91 diameter background field in all experiments. Fixation was central.…”