Animals have diversified and adapted to fill the numerous habitats and environments on this earth. The long-term goal of our studies is to elucidate mechanisms that drive these adaptive changes at the molecular and functional levels. We plan to accomplish this goal using vision as a model system. To identify critical amino acid (AA) changes that modify the wavelengths of maximal absorption (;maxs) of visual pigments, vision scientists analyze "contemporary" pigments. Experimental evolutionary biologists also manipulate "contemporary" pigments and infer the past. However, by ignoring the evolutionary processes of visual pigments, neither the molecular basis of spectral tuning in visual pigments nor the evolutionary mechanisms of visual pigments can be elucidated. Fortunately, the central unanswered questions in phototransduction and evolutionary biology can be solved simultaneously by genetically engineering and manipulating proper "ancestral pigments." Here, we propose to elucidate the molecular mechanisms that drive adaptive evolution of RH2, SWS1, and SWS2 pigments in vertebrates, which have;maxs of ~450-530, ~355-440, and ~400-460 nm, respectively. We approach the problem not only by determining the molecular basis of spectral tuning in visual pigments but also by establishing the relationships between organisms with different sets of visual pigments and their ecological environments. For each pigment group, we plan to 1) infer the AA sequences of ~15 ancestral pigments and engineer them and determine their;maxs, 2) infer AA changes that shift the;max, 3) identify the critical AA changes by mutating ancestral pigments, and 4) establish the universal chemical principle of the spectral tuning in visual pigments by using the quantum mechanical/molecular mechanical (QM/MM) methods, which have been proven to be highly effective. We shall also test the possibility of adaptive evolution of these visual pigments by examining whether the directions of the;max-shifts of visual pigments in various species match with the changes in the organisms'ecological environments. For this purpose, each of the three pigment groups with variable;maxs in multiple species will be classified into distinct classes according to their environments and tested for the possibility of adaptive evolution. Since virtually all fish SWS1 pigments examined to date are UV-sensitive, we also plan to search for violet-sensitive SWS1 pigments in different fishes, by surveying fishes that live at depths of 0-200 m and prey on small fishes and do not require UV vision for hunting. Considering the strong AA interactions that occur in SWS1 pigments, we also plan to elucidate how various critical AA changes could have accumulated during its evolution and learn the chemical structural preconditions required for UV pigments to become violet-sensitive and vice versa.
Using cell/molecular and quantum chemical methods, we study the structure-function relationships of visual pigments in various vertebrate species and their ancestors. Various levels of misfoldings of visual pigments induced by different amino acid changes in rhodopsins and other visual pigments are known to cause retinitis pigmentosa and other retinal dystrophies. Hence, the results obtained from our mutagenesis experiments and chemical structural computations of visual pigments together provide the fundamental information on the genetic bases of color vision defects and ocular diseases.
|Yokoyama, Shozo; Tada, Takashi; Liu, Yang et al. (2016) A simple method for studying the molecular mechanisms of ultraviolet and violet reception in vertebrates. BMC Evol Biol 16:64|
|Yokoyama, Shozo; Altun, Ahmet; Jia, Huiyong et al. (2015) Adaptive evolutionary paths from UV reception to sensing violet light by epistatic interactions. Sci Adv 1:e1500162|
|GÃ¼hmann, Martin; Jia, Huiyong; Randel, Nadine et al. (2015) Spectral Tuning of Phototaxis by a Go-Opsin in the Rhabdomeric Eyes of Platynereis. Curr Biol 25:2265-71|
|Yokoyama, Shozo; Starmer, William T; Liu, Yang et al. (2014) Extraordinarily low evolutionary rates of short wavelength-sensitive opsin pseudogenes. Gene 534:93-9|
|Yokoyama, Shozo; Xing, Jinyi; Liu, Yang et al. (2014) Epistatic adaptive evolution of human color vision. PLoS Genet 10:e1004884|
|Yokoyama, Shozo (2013) Synthetic biology of phenotypic adaptation in vertebrates: the next frontier. Mol Biol Evol 30:1495-9|
|Ryazantsev, Mikhail N; Altun, Ahmet; Morokuma, Keiji (2012) Color Tuning in rhodopsins: the origin of the spectral shift between the chloride-bound and anion-free forms of halorhodopsin. J Am Chem Soc 134:5520-3|
|Yokoyama, Shozo (2012) Synthesis of Experimental Molecular Biology and Evolutionary Biology: An Example from the World of Vision. Bioscience 62:939-948|
|Schnitzler, Christine E; Pang, Kevin; Powers, Meghan L et al. (2012) Genomic organization, evolution, and expression of photoprotein and opsin genes in Mnemiopsis leidyi: a new view of ctenophore photocytes. BMC Biol 10:107|
|Sekharan, Sivakumar; Katayama, Kota; Kandori, Hideki et al. (2012) Color vision: "OH-site" rule for seeing red and green. J Am Chem Soc 134:10706-12|
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