Phenotypic plasticity allows organisms to adapt quickly to local environmental conditions and could facilitate adaptive radiations. Cichlids have recently undergone an adaptive radiation in Lake Malawi where they inhabit diverse light environments and tune their visual sensitivity through differences in cone opsin expression. While cichlid opsin expression is known to be plastic over development, whether adults remain plastic is unknown. Adult plasticity in visual tuning could play a role in cichlid radiations by enabling survival in changing environments and facilitating invasion into novel environments. Here we examine the existence of and temporal changes in adult visual plasticity of two closely related species. In complementary experiments, wild adult Metriaclima mbenji from Lake Malawi were moved to the lab under UV-deficient fluorescent lighting; while lab raised M. benetos were placed under UV-rich lighting designed to mimic light conditions in the wild. Surprisingly, adult cichlids in both experiments showed significant changes in the expression of the UV-sensitive single cone opsin, SWS1, in only three days. Modeling quantum catches in the light environments revealed a possible link between the light available to the SWS1 visual pigment and SWS1 expression. We conclude that adult cichlids can undergo rapid and significant changes in opsin expression in response to environmental light shifts that are relevant to their habitat and evolutionary history in Lake Malawi. This could have contributed to the rapid divergence characteristic of these fantastic fishes.
A somatic activating mutation in AKT1, c.49G>A, pGlu17Lys, that results in elevated AKT signaling in mutation-positive cells, is responsible for the mosaic overgrowth condition, Proteus syndrome. ARQ 092 is an allosteric pan-AKT inhibitor under development for treatment in cancer. We tested the efficacy of this drug for suppressing AKT signaling in cells and tissues from patients with Proteus syndrome. ARQ 092 reduced phosphorylation of AKT and downstream targets of AKT in a concentration-dependent manner in as little as two hours. While AKT signaling was suppressed with ARQ 092 treatment, cells retained their ability to respond to growth factor stimulation by increasing pAKT levels proportionally to untreated cells. At concentrations sufficient to decrease AKT signaling, little reduction in cell viability was seen. These results indicate that ARQ 092 can suppress AKT signaling and warrants further development as a therapeutic option for patients with Proteus syndrome.
To determine the visual sensitivities of an organism of interest, quantitative reverse transcription–polymerase chain reaction (qRT–PCR) is often used to quantify expression of the light‐sensitive opsins in the retina. While qRT–PCR is an affordable, high‐throughput method for measuring expression, it comes with inherent normalization issues that affect the interpretation of results, especially as opsin expression can vary greatly based on developmental stage, light environment or diurnal cycles. We tested for diurnal cycles of opsin expression over a period of 24 hr at 1‐hr increments and examined how normalization affects a data set with fluctuating expression levels using qRT–PCR and transcriptome data from the retinae of the cichlid Pelmatolapia mariae. We compared five methods of normalizing opsin expression relative to (a) the average of three stably expressed housekeeping genes (Ube2z, EF1‐α and β‐actin), (b) total RNA concentration, (c) GNAT2, (the cone‐specific subunit of transducin), (d) total opsin expression and (e) only opsins expressed in the same cone type. Normalizing by proportion of cone type produced the least variation and would be best for removing time‐of‐day variation. In contrast, normalizing by housekeeping genes produced the highest daily variation in expression and demonstrated that the peak of cone opsin expression was in the late afternoon. A weighted correlation network analysis showed that the expression of different cone opsins follows a very similar daily cycle. With the knowledge of how these normalization methods affect opsin expression data, we make recommendations for designing sampling approaches and quantification methods based upon the scientific question being examined.
The family Cichlidae contains approximately 2000 species that live in diverse freshwater habitats including murky lakes, turbid rivers, and clear lakes from both the Old and New Worlds. Their visual systems are similarly diverse and have evolved specific sensitivities that differ along several axes of variation. Variation in cornea and lens transmission affect which wavelengths reach the retina. Variation in photoreceptor number and distribution affect sensitivity, spectral sensitivity and resolution. Probably their most dynamic characteristic is the variation in visual pigment peak sensitivities. Visual pigments can be altered through changes in chromophore, opsin sequence and opsin expression. Opsin expression varies by altering which of the seven available cone opsins in their genomes are turned on. These opsins can even be coexpressed to produce seemingly infinitely tunable cone sensitivities. Both chromophore and opsin expression can vary on either rapid (hours or days), slower (seasonal or ontogenetic) or evolutionary timescales. Such visual system shifts have enabled cichlids to adapt to different habitats and foraging styles. Through both short term plasticity and longer evolutionary adaptations, cichlids have proven to be ecologically successful and an excellent model for studying organismal adaptation.
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