Scientific Findings on Tetrachromacy
The Genes for Color Vision
The DNA of every normal-vision human observer includes inherited “opsin genes” which produce the visual pigments responsible for human color vision. Some of these visual pigments – for example, those sensitive to longer-wavelength and medium-wavelength light from the visible electromagnetic spectrum – arise from genetic sequences on the X-chromosome and are inherited in a recessive manner, while others that are sensitive to short-wavelengths of light are inherited in an autosomal dominant pattern via chromosome 7.Three human “photo”-pigment classes are typically involved in “photopic”, or daylight, processing of visual stimuli. In a normal retina, these photopigments reside within light-sensing “cone” cells that populate a retinal mosaic that includes “Long-wavelength sensitive”, “Medium-wavelength sensitive”, and “Short-wavelength sensitive” cone cell classes, (abbreviated “L-” “M-”, and “S-cones”).During the normal process of opsin gene inheritance and development, changes in the “usual” opsin gene sequences can occur. For example, mutations, deletions, and rearrangements of the genes that encode human L- and M- opsins can result in deficiencies in red-green color discrimination for some individuals. Not all mutations are bad, however, and some opsin gene sequence changes can modify the response properties of L- and M-cone cells while having no deleterious consequences for the perceptual processing of environmental color stimuli.Infrequently an individual may have specific opsin gene mutations that ultimately provide a genetic potential for the expression of four distinct classes of retinal photopigments. Such individuals can be said to have the genes, or the genetic basis, for retinal tetrachromacy.
What exactly are the genes, and what is the genetic basis, for retinal tetrachromacy?
While the length of the L- and M-opsin genes may seem great (~14,000 base pairs and ~12,030 base pairs, respectively), it is perhaps surprising that L- and M-opsin gene sequences differ by only15 loci along their protein coding gene sequences.This is especially interesting from a perceptual standpoint since those 15 coding sequence changes alone are responsible for a ~30 nanometer (nm) shift in cone sensitivity that is characteristic of an L-cone class “red” signal peak compared to that of an M-cone “green” signal peak. Interestingly, the majority of this 30nm difference in peak sensitivities between the normal red and green visual pigments is accounted for by differences in the genetic sequence at positions 180, 277, and 285.Indeed (and this is important for understanding potential tetrachromacy), the most influential of these three sequence positions involves single-nucleotide substitutions (or SNPs) at codon 180 of Exon 3. That is, at codon 180 a photopigment encoded from an Alanine allele has a maximal absorption that is shifted approximately 5nm towards the shorter wavelengths compared to the absorption peak of the “normal” form of the L-cone pigment encoded by a Serine variant (Merbs & Nathans, 1992, Asenjo et al., 1994).The frequency of opsin gene variations differs across the general human population, but it is estimated that in some groups L-cone pigment genes encode Serine 56% of the time and encode Alanine 44% of the time at position 180 (Gegenfurtner & Sharpe, 1999). The stable frequency with which the L-opsin codon 180 mutation is present in humans may suggest it is not likely a deleterious mutation of the opsin gene sequence.An individual possessing an L-opsin codon 180 tetrachromat genotype is special in that they possess opsin genes that encode both Serine and Alanine variants of the L-cone photopigment.
Further details on L-opsin codon 180 SNPs can be found at: Jameson, K. A. (2009). Human Potential for Tetrachromacy. Glimpse: The Art + Science of Seeing, 2.3, 82-91. And, http://www.glimpsejournal.com/2.3-KAJ.html.
Concetta Antico has the genetic basis for retinal tetrachromacy
In late 2012 Concetta Antico was evaluated both genetically and, to a lesser degree, behaviorally by Jay Neitz, Ph.D., Bishop Professor, Department of Ophthalmology, University of Washington. According to his genetic analyses (see Figure 1), Dr. Neitz suggests that Concetta’s “…L-opsin gene sequence shows an Exon 3 codon 180 polymorphism in the nucleotide sequence “KCT” at position 231, 232, 233 on the portion of her L-opsin gene electropherogram” (personal communication, May 28, 2014).
Figure 1. An excerpt of Concetta Antico’s L-opsin genetic sequence analysis shown as an electropherogram image. This image shows the computer generated output of automated sequencing. The curved peaks represent the intensity of the nucleotides (ddNTPs) observed in the DNA. The alphabet characters printed across the top of the peaks represent the observed gene sequence for the region. A central red arrow has been added to highlight a region of interest at position 180 on Exon 3 where the serine and alanine polymorphism is present on this L-opsin gene. Close examination of the curves under the red arrow shows two equally intense nucleotide traces present – a black curve traced over by an almost equal strength red curve. These represent high quality mixed bases as indicated by the magenta tagged signal over the highlighted “K” in the alpha-character sequence. This sequence is a product of DNA analyses conducted in the laboratory of Prof. Jay Neitz (Ophthalmology, University of Washington Medical School) during the November/December 2012 (personal correspondence dated 12/19/2012).
Proof of Tetrachromat Retinas?
Because of the complexity of genetic expression mechanisms, individuals with a genetic potential for tetrachromacy are often described as “putative retinal tetrachromats”. This is because presently there are no established methods to verify whether an individual with a “tetrachromat genotype” actually possesses normal, sufficient, populations of four distinct classes of cone photopigments expressed in their retinas. Adaptive Optics Scanning Laser Ophthalmoscopy technology (AOSLO) has in the last decade made huge advances towards in vivo imaging and analyses of the L-, M- and S-cone classes of the living human retinal mosaic, however, at present AO technology does not permit in vivo differentiation of the two, highly similar, variants of L-cone cell populations that retinal tetrachromats are presumed to possess.Despite current technology’s inability to confirm the presence of highly similar cone classes in a living retina, the scientific consensus, based on models of genetic expression mechanisms, is that otherwise normal color vision female individuals who genetically possess the L-opsin Exon 3, codon 180 polymorphism are thought to have a retinal mosaic with four functioning classes of cone photopigments. How the neural signals of these four classes of cones are processed by the brain remains the subject of debate.For now, at least, the proof of tetrachromat visual processing hinges on demonstrating what perceptual consequences may arise from having a retinal mosaic with four functioning classes of cone photopigments.Perceptual investigations of Concetta’s color processing features, and quantification of the manner in which it varies from the color processing of normal control observers, is a topic of on-going intense research interest.
For further details about color vision genetics and phenotypic expression of tetrachromacy, and its empirical demonstration can be found at: Glimpse Journal
Asenjo, A.B.; Rim, J.; Oprian, D.D. (1994). Molecular determinants of human red/green color discrimination. Neuron, 12, 1131-1138.
Gegenfurtner, K.R. and L.T. Sharpe (1999). Editors. Color Vision: From Genes to Perception. Cambridge University Press.
Merbs, S.L. & Nathans, J. (1992). Absorption spectra of human cone pigments. Nature, 356, 433-435.
Neitz, J. (2014). Ophthalmology, University of Washington Medical School. NeitzVision.com
This work is licensed to Concetta Antico under Creative Commons Attribution- Noncommercial-NoDerivatives Works 4.0 International License. June 13, 2014.
Antico, C. (2014). Scientific details of Concetta Antico’s genetic potential for tetrachromatic color vision.