Friday, April 3, 2009
Pax-6 gene
On page 194, Carroll talks about how different eye structures did not independently evolve multiple times, but rather they all stem from the same eye-building gene, known as the Pax-6 gene. A common ancestor of animals with the Pax-6 gene used the gene in the development of a primitive eye, and its descendents' eyes became different as time progressed. According to Carroll, this Pax-6 gene is responsible for eye development in a humongous amount of animals, including humans, fruit flies, mice, squids, planarians, and ribbon worms. Besides animals without eyes, do some animals NOT have the Pax-6 gene? Is there another gene in the animal kingdom that is responsible for eye development? If there is, how do the eyes of those animals differ than the eyes of animals with the Pax-6 gene?
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In Carroll’s discussion of the evolution of complexity he picks the perplexing example of the eyes to demonstrate how incremental changes from a single ancestor can morph into complex structures. The common misconception previously held by evolutionary scientists was the repeated evolution of the eye gave rise to the diversity in structures. However, upon closer examination of the genome of different organisms this theory can be easily refuted. In figure 8.2, which maps out the pax-6 protein sequence genome of a fruit fly, Mouse, and Human, the beginning of the sequence (LQRNRTSFT) and the end of the sequence (SNRRAKWRREE) are exactly identical, among other similarities. Carroll states that this similarity can not merely be coincidence. He cites the experiment of interchanging mouse Pax-6 genes and fly Pax-6 genes to show how closely related the function is of the gene proving that there “existed a primitive eye in the common ancestor of most animals” (197). However, that still does not mean that all organisms have this gene because not all organisms harness the power of vision as a survival force.
ReplyDeleteIn the experiment “Isolation and expression of a Pax-6 gene in the regenerating and intact Planarian” conducted by scientists by of the University of Barcelona, one of the conclustions of their experiment was the low levels of expression of the Pax-6 gene , because of the lack of a “bona fide Pax-6 homolog,” in diploblastic organisms ; thus, dipoblastic organisms may lack the Pax-6 gene. The observation that a true Pax-6 homolog is present in planarians but has not been identified in diploblastic animals suggests that Pax-6 might be typical for triploblasts, and the appearance of additional Pax genes may have coincided with the appearance of increasingly complex body plans.
In the case of eye development, about 2,000 different genes must be “turned on” at the proper time and place for eyes to develop properly.Carroll mentioned several of the genes other than Pax-6 involved with eye development: eyeless gene (amphibians) and aniridia (humans). Mice with defects in the Pax-6 gene have small eyes and humans with defects in their aniridia gene lack an iris.
Natural antisense transcripts, NATs, (group of RNAs encoded within a cell that have transcript complementarity to other RNA transcripts) may also be involved in eye development. In mouse there are eight NATs associated with transcription factors (Pax6, Pax2, Six3, Six6, Otx2, Crx, Rax and Vax2) that play an important role in eye development and function. These newly-identified NATs overlap with the mature processed mRNAs or with the primary unprocessed transcript of their corresponding sense genes, are predicted to represent either protein coding or noncoding RNAs and undergo extensive alternative splicing. Expression studies, demonstrate that most of these NATs display a specific or predominant expression in the retina, particularly at postnatal stages. In an experiment, scientists found a reduction of the expression levels of the NAT Vax2OS in a mouse mutant carrying the inactivation of Vax2, the corresponding sense gene. In addition, they overexpressed another NAT, CrxOS, in mouse adult retina using viral vectors and observed a significant decrease in the expression levels of the corresponding sense gene, Crx. These results suggest that these transcripts are functionally related to their sense counterparts and may play an important role in regulating the molecular mechanisms that underlie eye development and function in both physiological and pathological conditions.
Another gene required for eye development, the counterpart of eyeless is eyelid. Eyelid antagonizes wingless signaling during Drosophila development and affects patterning of the eye imaginal disc. Eyelid was originally isolated as a suppressor of a dominant mutation in the rough gene roughDOMINANT. Eye discs from roDOM third-instar larvae display a "furrow-stop" phenotype, the unusual presence of mature ommatidia that contain a full complement of photoreceptor cells in the anterior-most ommatidial row, and the loss of dpp expression in the furrow. Surprisingly, an analysis of eye discs from larvae heterozygous for both roDOM and eyelid reveals that the observed increase in eye size is not attributable to relief of the roDOM-induced block to furrow progression in the central region of the disc. Rather, photorecepter differentiation reinitiates at the dorsal and ventral edges of these discs. This produces two ommatidial fields, each preceded by decapentaplegic expressing furrows, which move anteriorly, fusing later along the midline. The mechanism of roDOM suppression by eyelid suggests that eyelid is most critical at the lateral edges of the disc, regions in which wingless has been shown to inhibit precocious differentiation. A reduction of wingless has the opposite effect on roDOM, reducing the eye size and the extent of photoreceptor differentiation along the disc margins. Thus eyelid mutations show opposite effects to those of wingless mutations, suggesting that eyelid may normally function as an antagonist of wg signaling. Eyelid is also required for embryonic segmentation
Another gene involved in the in formation of the optic placode during embryonic development is termed eye absent gene, or clift. The eyes absent gene, recently and more correctly termed clift, is required at an early stage in development of the compound eye. Eya is not expressed in the embryonic eye primordia or in eye discs during the first larval instar, suggesting that unlike eyeless, eya is not involved in determining early commitment to eye cell fate. In fact the newly discovered mammalian eya homolog has been shown to be regulated by Pax6, the vertebrate homolog of Drosophila Eyeless. In Drosophila eya mutants, progenitor cells in the eye disc undergo programmed cell death anterior to the morphogenetic furrow, rather than proceeding along the developmental pathway leading to retinal differentiation. Thus the absence of eyes is not due to a lack of precursors but to death of those precursors. A low level of cell death normally occurs at this stage, suggesting that eya activity influences the balance between cellular differentiation and death, that is, Eya has a cell survival function. Molecular analysis identifies Eya as nuclear protein expressed in progenitor cells prior to differentiation. It thus appears that eyes absent activity is required for the survival of eye progenitor cells at a critical stage in morphogenesis.
These only name a few of the many genes involved with the variety seen in the diversity of eye structures.
Sources:
http://www.sdbonline.org/fly/aimorph/eye.htm
http://hmg.oxfordjournals.org/cgi/content/abstract/ddi084v1
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=15175
While Gehring’s research provided evidence for derivations of the Pax-6 being responsible for the formation of eyes, there are also experiments that have shown that there are organisms without the Pax-6 genes, yet have eyes. In the work summarized and compiled in the PNAS article ”Isolation and expression of a Pax-6 gene in the regenerating and intact Planarian Dugesia(G)tigrina” by several scientists, it was found a true Pax-6 gene has yet to be found in dipoblastic animals, yet Planarians possess primitive eyes.
ReplyDeleteThe fruit fly gene known as Dachshund can trigger the formation of eyes of extra eyes, just like how Gehring activated the Pax-6 gene in areas where it was normally inactive in one of his experiments. Dachshund is a necessary nuclear factor (a protein complex that acts as a transcription factor) for determining cell differentiation in the eyes, legs, and nervous system of Drosophilia. It also works in conjunction with the Eyes Absent gene (clift) and Sine Oculis for eye formation. The eyes absent gene is required for the early development of the compound eye (the eye being made up several thousand “eye units”; typical of insects). Sine oculis works play a role in eye formation by being present at the birth of the eye primordium (the eyes’ earliest recognizable stage of development) and has a direct role in this process.
The interaction of the eyes give rise to compound eyes unlike the eyes that arise from the Pax-6 genes. Compound eyes have several thousand photoreceptor units that are pointed at different angles, resulting in a wide range of view, unlike vertebrate eyes that have a lens that refracts light from different angles on to the retina region. Drosophilia specifically have apposition compound eyes, which gather a number of images from each eye and combining them in the brain; whereas in vertebrates, the retina receives a flipped, inverted image where the photoreceptor cells translate light into electrical impulses by means of phototransduction to be sent to the brain.
http://www.sciencenews.org/sn_arc97/5_10_97/bob1.htm
http://www.genecards.org/cgi-bin/carddisp.pl?gene=DACH1
http://www.sdbonline.org/fly/newgene/eyesab1.htm
http://www.sdbonline.org/fly/dbzhnsky/dachsud1.htm
http://www.sdbonline.org/fly/neural/sineocul.htm
http://en.wikipedia.org/wiki/Eye#Compound_eyes
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=15175