Page 98 - Genetics_From_Genes_to_Genomes_6th_FULL_Part2

7.6 A Comprehensive Example: Mutations That Affect Vision 257

blue-receiving protein are the same as those found in rho- early loss of rod function, followed by a slow progressive
dopsin; the rest are different and account for the specialized degeneration of the peripheral retina. Figure 7.33a shows
light-receiving ability of the protein (Fig. 7.32b). The gene the location of the amino acids affected by these muta-
for the blue protein is on chromosome 7. tions. These amino acid changes result in abnormal rho-
Similarly related to rhodopsin are the red- and green- dopsin proteins that either do not fold properly or, once
receiving proteins in the red and green cones. These are folded, are unstable. Although normal rhodopsin is an
also single polypeptides associated with retinal and embed- essential structural element of rod cell membranes, these
ded in the cell membrane, although they are both slightly nonfunctional mutant proteins are retained in the body of
larger at 364 amino acids in length (Fig. 7.32b). Like the the cell, where they remain unavailable for insertion into
blue protein, the red and green proteins differ from rhodop- the membrane. Rod cells that cannot incorporate enough
sin in nearly half of their amino acids; they differ from each rhodopsin into their membranes eventually die. Depend-
other in only 15 of their 364 amino acids. Even these small ing on how many rod cells die, partial or complete
differences, however, are sufficient to differentiate the blindness ensues.
spectral sensitivities of red and green cone cells. The genes Other mutations in the rhodopsin gene cause the far
for the red and green proteins both reside on the X chromo- less serious condition of night blindness (Fig. 7.33a). These
some in a tandem head-to-tail arrangement. Most people mutations change the protein’s amino acid sequence so that
have one red gene and one to three green genes on their the threshold of stimulation required to trigger the vision
X chromosomes (Fig. 7.32c). cascade increases. With the changes, very dim light is no
longer enough to initiate vision.
Evolution of the rhodopsin gene family
The similarities in structure and function among rhodopsin
and the three rhodopsin-related photoreceptor proteins sug- Figure 7.33 How mutations modulate light and color
gest that the genes encoding these polypeptides arose by a perception. (a) Amino acid substitutions (black dots) that disrupt
series of gene duplication events in which the duplicated rhodopsin’s three-dimensional structure result in retinitis pigmentosa.
copies subsequently diverged through the accumulation of Other substitutions diminishing rhodopsin’s sensitivity to light cause
mutations. Many of the mutations that promoted the ability night blindness. (b) Substitutions in the blue pigment can produce
tritanopia (blue color blindness). (c) Red color blindness can result
to see color must have provided selective advantages to from particular mutations that destabilize the red photoreceptor.
their bearers. (d) Unequal crossing-over between the red and green genes can
Biologists can infer the evolutionary history of these change gene number and create genes that specify hybrid
duplications from the relatedness of the genes and protein photoreceptor proteins.
products. The red and green genes are the most similar, dif- (a) Retinitis Night
fering by fewer than five nucleotides out of every hundred. pigmentosa blindness
This fact suggests they diverged from each other only in the
relatively recent evolutionary past. The less pronounced Ala292 Gly
amino acid similarity of the red or green proteins with the
blue protein, and the even lower relatedness between rho- Gly90 Asp
dopsin and any color photoreceptor, reflect earlier duplica- Rhodopsin Rhodopsin
tion and divergence events (Fig. 7.32d).
(b) Tritanopia (c) Red colorblindness
Pro264
Ser
How Mutations in the Rhodopsin Gene
Family Affect the Way We See Gly79 Cys203 Arg
Arg
Mutations in the genes encoding rhodopsin and the three
color photoreceptor proteins can alter vision through many Red photoreceptor
different mechanisms. These mutations range from point Blue photoreceptor
mutations that change the identity of a single amino acid in (d) Unequal crossing-over
a single protein to larger aberrations that can increase or
decrease the number of photoreceptor genes.

Mutations in the rhodopsin gene
At least 29 different single nucleotide substitutions in the
rhodopsin gene cause an autosomal dominant vision dis-
order known as retinitis pigmentosa that begins with an