Conservation of the "Control Switch" Gene for Eyes
Phylogenetic analysis has shown that eyes have independently evolved dozens of times in the history of life. (See the Evolution and Phylogenetics unit.) For example, there are striking differences between the eyes of insects and those of vertebrates. Vertebrates have a camera eye, consisting of a light-sensitive retina, a lens, and a series of muscles used for adjusting focus. In contrast, insects have compound eyes, consisting of numerous light-sensitive ommatidia.
Biologists have learned about the genetics of the visual system in insects by studying mutations that affect eyes in Drosophila. Mutants of the eyeless gene in Drosophila have reduced eye size, with the extent of the reduction depending on the allele. The eyeless gene is normally expressed only in the tissues that become the eyes. Recall that genes in Drosophila are named for the phenotypes of their mutations and not their normal function. What is remarkable about eyeless is that its expression can induce eyes to grow where they ordinarily don't. Members of Walter Gehring's lab in Switzerland created transgenic flies which could express the eyeless gene in various places in the developing fly. By expressing eyeless where it is normally not present (ectopic expression), they were able to produce flies with eyes on their antennae, legs, wings, and various other places. So, eyeless looks like a control switch gene for making eyes (Fig. 8).
These same researchers also used databases to search for homologous genes of eyeless in mammals. (See the Genomics unit.) They found that the eyeless gene in Drosophila was strikingly similar (more than ninety percent sequence identity) to the Pax-6 gene in mammals. This Pax-6 gene is also called Smalleyes in mice (where mutants have small eyes) and Aniridia in humans (where mutants lead to deficient development of iris).
Now here's the really fascinating part! Gehring's lab did the same ectopic expression experiment but with the mammalian homologue of eyeless. They produced flies with eyes on their antennae, legs, wings, and various other places. The eyes produced were the compound eyes of flies but the machinery for making these eyes could be turned on by mammalian eyeless protein. Despite the independent evolution of eye structure and over
550 million years of independent evolution, the "control switch" for eye development has been conserved.
There are differences between the role eyeless plays in flies and mammals. Unlike in Drosophila, where eyeless is not required for viability, homozygotes for the deletion of eyeless are inviable in mammals. Furthermore, this gene is expressed in regions of the mammalian forebrain. This is strong evidence that eyeless has functions in addition to eye development.
Sonic Hedgehog
Researchers discovered that vertebrates have a homologue to the Drosophila hedgehog gene. They named the vertebrate homologue "Sonic Hedgehog" after the video game character Sonic the Hedgehog. This gene, which encodes a ligand, has diverse functions, including limb development, patterning of the neural tubes (and hence the brain), and differentiation of regions in the gut. How does it work? Cells of the developing notochord send out Sonic Hedgehog signals to the spinal cord. These cells respond to the signaland then differentiate into the ventral part of the spinal cord, which makes the motor neurons that permit muscular activity. Across mammals this gene is highly conserved; the mouse and human Sonic Hedgehog proteins are ninety-two percent identical at the amino acid level.
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