One of the major goals of evolutionary biology is to elucidate the mechanisms of natural selection at the genotype, phenotype and organismal levels. This is a difficult problem to solve for it is not easy to relate phenotypes to specific genotypes unambiguously and, at the same time, to relate the phenotypic changes to the changes in the organisms' ecological and physiological environments. Because of this difficulty, molecular evolutionists heavily rely on statistical analyses of DNA sequence data, which is based on the fundamental principle: "to detect positive Darwinian selection, it is necessary to show that dn is significantly greater than ds (1)." However, these statistical analyses provide only biological hypotheses and these results must eventually be examined using experimental methods.
Visual adaptations are closely linked to organisms' environments and behaviors, showing that natural selection has played an important role in shaping these phenotypes. In the 1980s, there were two critical advances in the molecular biology of vision: first, the cloning of the human opsin genes that encode visual pigments and are responsible for dim-light and color vision and, second, the development of functional assays for visual pigments. Combining extensive data on ecology and molecular genetic data of visual pigments, vision became arguably the best model system to study phenotypic adaptation (2). However, our knowledge on the evolutionary mechanisms producing various phenotypes, including color vision, are still superficial. Today, therefore, it is critical to understand the causes for the slow progress and then rectify the traditional ways of studying the molecular mechanisms of phenotypic adaptation.
For over the last 20 years, we have been studying the molecular genetics and evolution of color vision in a diverse range of species, from fish to human. These analyses have significantly improved our understanding of adaptive evolution of vision. If we truly want to understand the genotype-phenotype relationship, we need to go one step deeper. Namely, even if all adaptive mutations are identified using experimental methods, their actual roles in the functional differentiation of phenotypes are still unclear. Fortunately, the precise roles of amino acid changes in adaptive evolution of visual pigments can be studied using quantum mechanical/molecular mechanical (QM/MM) calculations (3). This method uses the homology models established by using the crystal structure of bovine rhodopsin as a template. Several years ago, in collaborations with Theoretical Chemist Professor Keiji Morokuma (Chemistry Department, Emory University), we also started the quantum chemical evolution of vision.
To suppose that the eye, with all its inimitable contrivances for adjusting the focus to different distances, for admitting different amounts of light, and for the correction of spherical and chromatic aberration, could have been formed by natural selection, seems, I freely confess, absurd in the highest possible degree. Yet reason tells me, that if numerous gradations from a perfect and complex eye to one very imperfect and simple, each grade being useful to its possessor, can be shown to exist; if further, the eye does vary ever so slightly, and the variations be inherited, which is certainly the case; and if any variation or modification in the organ be ever useful to an animal under changing conditions of life, then the difficulty of believing that a perfect and complex eye could be formed by natural selection, though insuperable by our imagination, can hardly be considered real.