Evolutionary significance of color vision gene therapy

An aspect of the color blindness story that we didn't mention in our earlier post, but should have, is the evolutionary implication. Like humans, the monkeys in the experiment have three types of cone cells, L cells or cells that are sensitive to light of long wavelength, M, or medium wavelength sensitive cells and S, or short wavelength (blue) sensitive cells. Color blindness occurs in primates missing the L or M sensitive photopigment. In this experiment, the investigators introduced a photopigment gene that was expressed preferentially in M cone cells, into animals that were red-green color blind.

We quote here from the paper (Gene therapy for red-green colour blindness in adult primates, Mancuso et al., Nature, advance online publication 16 September 2009).

Classic experiments in which visual deprivation of one eye during development caused permanent vision loss led to the idea that inputs must be present during development for the formation of circuits to process them. From the clear change in behaviour associated with treatment, compared both between and within subjects, we conclude that adult monkeys gained new colour vision capacities because of gene therapy. These startling empirical results provide insight into the evolutionary question of what changes in the visual system are required for adding a new dimension of colour vision. Previously, it seemed possible that a transformation from dichromacy to trichromacy [from seeing 2 colors to seeing 3, which, in combination, allows us to see the full spectrum of color that we do] would require evolutionary/developmental changes, in addition to acquiring a third cone type. For example, L- and M-opsin-specific genetic regulatory elements might have been required to direct the opsins into distinct cone types⁹that would be recognized by L- and M-cone-specific retinal circuitry, and to account for cortical processing, multi-stage circuitry might have evolved specifically for the purpose of trichromacy. However, our results demonstrate that trichromatic colour vision behaviour requires nothing more than a third cone type. As an alternative to the idea that the new dimension of colour vision arose by acquisition of a new L versus M pathway, it is possible that it exploited the pre-existing blue-yellow circuitry. For example, if the addition of the third cone class split the formerly S versus M receptive fields into two types with differing spectral sensitivities, this would obviate the need for neural rewiring as part of the process of adopting new colour vision.

So, in these monkeys, M cone cells that were previously not sending signal to the brain began to do so after a functional photopigment gene was introduced and activated in the retina. Apparently no new brain circuitry was required for these monkeys to begin seeing color, because they began to do so at the same time that high levels of the expressed transgene were detectable. Thus, the investigators suggest this experiment is a reprise of the evolution of color vision, and that it didn't require new cortical function or circuitry but only the addition of a third cone type.

The latter conjecture is worth thinking about, but the basic color vision system is much older and many studies have been done about the gene arrangement, spectral sensitivity, and adaptive aspects of the system. It is not a simple evolution, much less a story of novel progress from simple to complex, not even in primates. But if it can help understand how eye-to-brain wiring and perception works, it will be a step forward.