Red-Green Colourblindness

Mutations that arise spontaneously usually occur as a result of unrepaired errors during replication, as discussed in Chapter 4, or as transposable element movement, as discussed in Chapter 3.  However, a few mutant alleles arise during recombination; the most familiar example is red-green colourblindness in humans.  The same process that produces red-green colourblindness has also been an important evolutionary force for shaping genomes and gene families.

The primary photoreceptors in our retina are a family of proteins known as the opsins proteins; the opsins in our cone cells absorb light of different wavelengths and allow us to see colors.  Opsins that absorb short wavelengths are the blue opsins; the blue opsin gene is autosomal and is not involved in red-green colourblindness.  Opsins that absorb long wavelengths are called the red opsins, while those that absorb medium wavelengths are called the green opsins; strictly speaking, the maximum absorbance for the red opsins is now known to be in the yellow spectrum, but they are more sensitive to the longwave red light than are the green opsins so the original name has stuck.  The genes for the red and the green opsins are X-linked, and are immediately adjacent to each other on the chromosome.  The genes are 96% identical in DNA sequence; in fact, the regions between the genes are also highly similar in DNA sequence.  There is usually a single red opsin gene and one to four green opsin genes in tandem duplication as shown in Figure B9-4 Part A.

When the X chromosomes synapse, the DNA sequence identity in this region is high enough that the two homologues can misalign, as shown in Figure B9-4 Part B.  If a crossover occurs with these misaligned chromosomes, the two recombinant chromosomes are not the same as one another; this is known as unequal crossing over.  Depending on where the crossover occurred in the gene family, outcome can be a deletion of one red gene or the green gene, or the generation of a hybrid red-green gene.  Since these are X-linked genes, males who inherit such an X-chromosome from their mothers will be red-green colourblind.  The majority of red-green colourblind males have a normal red opsin gene followed by a hybrid red-green gene, a condition known as deuteranomaly.  Smaller percentages have the red gene deleted (protanopia), a hybrid red-green gene with no normal red gene (protanomaly), or a single red gene with the green gene deleted (deuteranopia), depending on where the unequal crossover occurred in these genes.

Because red-green colourblindness arises from unequal crossing over rather than a replication error or a transposition event like most other mutations, the frequency is fairly high; approximately 8% of males are red-green colourblind, a frequency that is similar (although not identical) among most human populations. As many men can attest, the condition is not life-threatening and most learn to adjust at an early age.

While red-green colourblindness is the most familiar example of unequal crossing over for most of us, it is far from the only one, and probably not the most significant one for evolution and genetics.  The misalignment of homologues can occur whenever there are duplicate genes or sequences in the genome.  This occurs with many gene families like the opsins or the globins, or with many other repeat sequences in eukaryotic genomes including transposable elements.  The genomes of metazoans are littered with repeat sequences that are a source for misalignment and duplication/deletion chromosomes.  Unequal crossing over is the most likely origin of the duplication chromosomes that result in the expansion of gene families and the duplication-divergence pattern for new genes.