Tuesday, April 14, 2009
Tool Kit Genes
On pg. 206, Carroll discusses the differences in the development of pelvic spines in three spine stickleback fish. One type is "a "open-water, full spined form", while the other is a "shallow water, bottom-dwelling, reduced-spined form". The tool-kit gene responsible for spine reduction in the latter is known as Pitx1. Define what a tool-kit gene is. How does Pitxl control gene expression? What are other methods of gene expression? How is it possible that individuals of these two populations can mate when they have different features and different expressed genes?
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A tool-kit gene is a gene that has several jobs in the development of a species, controls other genes, and has counterparts in other animals. Tool-kit genes are the several genes that serve as a “tool” for the development of many other proteins by arranging genes in a different manner, showing the complexity of evolution.
ReplyDeletePitx1 gene regulates gene expression by noncoding DNA sequences. The Pitx1 gene reduces fishes’ pelvic skeleton without affecting other parts of the body where Pitx1 also functions. The Pitx1 proteins do not have any differences in the sequence between “open-water, full-spined form,” and “shallow-water, bottom-dwelling, reduced-spined form.” The changes in the gene expression are caused by the change in the noncoding DNA sequences that are regulatory. Carroll describes some of the noncoding DNA as “switches” that determines the use of a gene in different body parts. The function of the “switches” depend on the DNA sequences and mutations in these “switch” genes cause changes in their function. Since these DNA sequences determine a function of the protein expressed, the change in one “switch” does not affect all other structures and functions. The pelvic-reduced stickleback fish does not use the Pitx1 gene in pelvic fin development. Changes in the switch that govern the use of the hindlimb allowed the selective reduction of this part of the fishes’ skeleton. A switch in the noncoding DNA sequence is mutated and the gene for pelvic fin development could not be expressed.
The full-pelvis fish and the pelvis-reduced fish can mate, because they are not different species. Even though one has lost the pelvic fin while the other still preserved it, the fish still have the same genetic materials that make them the same species. The difference in the noncoding Pitx1 gene does not affect the gene expression of other functions, just resulting in the inexpression of a particular gene. After all, the coding Pitx1 DNA sequences do not differ at all. It is not the different expression of genes; it is just the lack of fully expressing one’s genes compared to the other population. It is unlike the horse and a donkey in which they can produce offspring, but the offspring are sterile, showing that the gene expression of these two species is too different to produce a viable offspring. In the horse and a donkey, the gene expressions and DNA sequences differ too much for them to mate and survive. The full-pelvis and pelvis-reduced fish, on the other hand, are of the same species and can produce viable offspring. Their gene expressions are the same, with one lacking some gene expressions than the other. There are no new genes created that make the full-pelvis fish’s genome too different from the pelvis-reduced fish.
http://www.geocities.com/moredonkeys/aboutmules.html
http://www.nature.com/nature/journal/v428/n6984/full/nature02415.html
Tool kit genes are also known as homeobox genes. Biologists were searching for how the blueprints of the repeated body patterns, found in many different structures of animals, developed into the embryo. The development of the body plan is controlled by a small number of genes, and these genes are virtually the same in all animals. Scientists discovered this when these genes were mutated. For example, in fruit flies, if a gene is mutated and its legs form where the antennae should form, then the biologists can search for which gene that mutation lays on and connect it back to the tool- box gene. These genes that are called tool-box genes contain the developmental instructions for the body plan of the animal. The DNA code directs the cell to make chemical sequences, which regulate other genes that affect the position of cells forming the embryo.
ReplyDeleteThe Pitx1 gene stands for paired-like homeodomain transcription factor 1. It acts as a transcriptional regulator involved in hormone-regulated activity. Pitx1 is a homeobox gene with orthologs found in all vertebrates. Orthologs are homologous genes in different speices, so they are genes that have descended from a gene in the common ancestor of those species. It contains three exons that encode a protein that is 283 amino acids long. This protein is a transcription factor that regulates the expression of other genes involved in the differentiation and function of the anterior lobe of the pituitary gland, jaw development, development of the thymus and some types of mechanoreceptors, and the development of the hind limbs. Pitx1 is controlled by regulatory genes, promoters and enhances, that are specific to each region. When mutations occur in the coding regions of Pitx1 is can be lethal, but when mutations occur in the noncoding regions of the gene it may not be lethal but damages do occur to that organism. Pitx1 is required for the proper development of the pelvic girdle with associated bones that all vertebrates have. These bones make pu the pelvic fins of fishes and the hind legs of the tetrapods. Therefore, a mutation in the noncoding region of the Pitx1 gene causes the different structures of the pelvic bones of the marine stickleback.
These fish have prominent spines that jut out from their pelvic region and they have spines along their back which help protect them from being eaten by predators. In marine sticklebacks, the Pitx1 gene is expressed in the thymus, mechanoreceptors, and in the pelvic region. Therefore, this single gene mutation can and does lead to a major change in the phenotype of the sticklebacks. The three different types of sticklebacks have a reduction of skeletal armor. Regulatory mutations of the Pitx1 are responsible for this loss of the pelvic structures.
The different types of sticklebacks can mate because they are of the same species and do have the same DNA. Their different in their pelvic spines is simply due to the mutation of the Pitx1 gene, and not do the difference of genes. Mutations occur in humans all of the time, which lead to disorders or different features, but all humans can still mate because their DNA coding is the same with just a few mutations.
http://jhered.oxfordjournals.org/cgi/content/full/esm066v1
http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/M/Mutation_and_Evolution.html
http://en.wikipedia.org/wiki/PITX1
http://www.pbs.org/wgbh/evolution/library/03/4/l_034_04.html
Tool Kit Genes
ReplyDeleteOn pg. 206, Carroll discusses the differences in the development of pelvic spines in three spine stickleback fish. One type is "a "open-water, full spined form", while the other is a "shallow water, bottom-dwelling, reduced-spined form". The tool-kit gene responsible for spine reduction in the latter is known as Pitx1. Define what a tool-kit gene is. How does Pitxl control gene expression? What are other methods of gene expression? How is it possible that individuals of these two populations can mate when they have different features and different expressed genes?
Genetic tool kits are also known as homeobox genes. These genes are crucial to the development because they contain the developmental instructions for the body plan. This code helps direct the homeobox gene that directs the cell to make chemical sequences which then regulate other genes that affect the positioning of the cell in an embryo. There are at least 24 different homeobox genes that are most active during the embryonic development of an organism. It helps with the identity of the body parts in an organism. They are said to play a crucial role in anterior-posterior gradient in the egg of the fruit fly Drosophila melanogaster.
The homeobox was originally discovered and understood as a conserved DNA motif that has similarity through all cellular organisms with about 180 base pairs. The protein translated from this DNA strand is about 60 amino acids long and some say that the homeodomain is a DNA binding domain that occurs in proteins that are usually transcription factors that affect the transcription of DNA strands and affect the outcome of the translation of mRNA strands.
A specific experiment was conducted to research the significance of the homeobox genes. In 1994, Gehring put a moue’s eyeless homeobox gene into a fruit fly and the fruit fly also developed normal fruit fly eyes. This implication infers that this homeobox gene must be common in most organisms and that they must all then stem from a single common ancestor like the LUCA. LUCA most likely passed down this gene to affect body formation in all descended organisms.
Pitxl has been the study in order to further research the importance and significance of the homeobox genes. Pitxl is a homeodomain factor that exhibits preferential expression in the developing of certain body parts. A study done on mice where the pitxl gene was deleted from mice displayed “striking abnormalities in morphogenesis and growth of both hind limb and mandible” showing an obvious defect in the mice.
How does it work? Well it is believed that the homeodomain, the pitxl, is part of the protein that binds to DNA when the protein functions as a transcription factor. This part forms three α helices with one of them fitting neatly into the DNA helix. It is other parts of the protein domain that determines which gene is regulated by the protein. This other domains interact with other transcription factors that help the protein recognize specific promoters with the TATA box and bind and transcribe. Most likely the homeodomain of the protein help regulate the development by coordinating the transcription of batteries of developmental genes, switching them on or off. That means if the homeodomain of a certain protein is turned off, like if Pitxl is turned off, then that specific protein would not read the DNA code which would then result in a lack of translation for a specific protein that could lead to the development of certain body parts. So in the case of the stickle back fish, the Pitxl could have switched on or off a protein to help transcribe the DNA code to translate into specific proteins to develop into either the full spine or reduced spine.
A method to regulate gene expression is the modification of the actual DNA through chemicals. Methylation of DNA is a way to “silence” the gene. This involves the addition of a methyl group to DNA which is adding a methyl group to the number 5 carbon of the cytosine pyramiding ring. This silences gene expression because first, the methylation may physically impeded the binding of transcriptional proteins to the gene and secondly and more likely the methylated DNA will be bound by proteins known as methyl- CpG- binding domain proteins. MDB the recruit additional proteins to the locus such as histone deacetylases and other chromatin remodeling proteins that can modify histones and form compact inactive chromatin which is called silent chromatin.
Other factors are factors such as the common transcription factors such as repressors, activators, TATA box location, and then there are post transcription factors such as capping, splicing, and the additional poly (a) tail. There are numerous factors that result in gene expression that’s why the development of evolution is difficult to track and study. Many factors also reinforce that evolution depends on time, selection and CHANCE.
http://www.pbs.org/wgbh/evolution/library/03/4/l_034_04.html
http://www.cbt.ki.se/groups/tbu/homeo.html
http://cat.inist.fr/?aModele=afficheN&cpsidt=20029442
http://en.wikipedia.org/wiki/DNA_methylation
http://en.wikipedia.org/wiki/Regulation_of_gene_expression
Carroll writes that pelvic spines decreases in bottom-dwelling populations were due to less development of the pelvic fin bud. This in turn, was due to the tool-kit gene called Pitx1. The tool kit gene is a gene that controls other genes and is a homeobox gene, or in short, hox genes; tool-kit genes “are shared by all animals, and differences in form come from changing the way they are used” (source: http://www.bioone.org/doi/full/10.1641/0006-3568%282005%29055%5B0898%3ATNJSS%5D2.0.CO%3B2) in development. In fishes, the tool-kit gene has several jobs in development, and in mice, it “helps make the hindlimb different from the forelimb” (Carroll 206), limbs being a repeated structure. In essence, tool kit genes can construct very complex organisms from a simple egg.
ReplyDeleteAs stated before, there are many types of different tool-kit genes that can take part in construction of the organism’s limbs, heart, and so on. Additionally, since many parts of the tool kit genes are shared amongst many different animals, this could indicate some sort of last universal common ancestor, the LUCA. The existence of a LUCA can also explain similarities in animals such as vertebrates, fishes, birds, and so on, and arthropods, such as centipedes and crustaceans; both these groups have repeating segments. Also, in the book, Carroll reminds the reader that the “pelvic fin was the evolutionary forerunner of the hinidlimb of four-legged animals” (Carroll 206). The origin would then conclusively add up to more than 500 million years ago, before the Cambrian explosion that “marked the emergence of large, complex, animal bodies” (source: http://www.biology.lsu.edu/heydrjay/1202/Chapter24/TheOriginsofForm.html).
Due to the principal of evolution, when organisms evolved and separated into different branches, their tool kit gene became slightly altered in order to serve specific functions in the organism but in essence, many different animals possess the same tool kit, such as the mouse and the stickleback fish. Increases in complexity can logically be thought to be the result of completely new genes. However, in this case, it was due to the evolution of an old gene, the tool kit gene, that was originally from the LUCA; most genes involved in the construction of the organism’s body, such as Pitx1 is involved in the construction of the sticklebacks’ pelvic spines, existed before the emergence of animal body plans and more complex vertebrates. The existence of the same gene in different organisms but different functions exhibits continuity and change; the organism specifically changed the function of the gene to fit their development and body plan. This is exhibited because the “Pitx1 proteins of the pelvic-reduced and full pelvic forms . . . [do not possess] a single difference in the protein sequence” (Carroll 206).
Homeobox genes direct the development from an organism, from zygote to adult. Like Scotty said, there are twenty-four homeobox genes that are involved in the embryonic development of an organism and “helps with the identity of the body parts in an organism . . . [and] are said to play a crucial role in anterior-posterior gradient in the egg of the fruit fly Drosophila melanogaster” (Lu).
Pitx1 controls gene expression because in addition to a coding part that it has, it also possess non-coding bits of DNA that are regulatory. Pitx1 can “decide” which gene to use by using “switchlike devices” (Carroll 206) and they have many different switches that control the way a gene can be used. It is also important to note that alterations of a switch will not cause changes in the other switches. In the stickleback fish, the reducing of the pelvic skeleton is because of a change in function of a switch controlling Pitx1 during development and can be seen in Figure 8.6. Gene expression can also include transcription and translation. Both are major processes in linking genes to proteins; transcription is the synthesis of RNA under the direction of DNA while translation is the actual synthesis of a polypeptide, which occurs under the direction of mRNA.
On an ending note, it is also interesting to observe that the stickleback fish is hunted by predators; near the surface of the water, long spines help protect the stickleback from being swallowed by large predators, such as larger fishes, but, long pelvic spines are a liability in deeper seas as dragonfly larvae prey on stickleback offspring by grabbing them by their spines. These two groups of predators affect whether full pelvis or reduced pelvis stickleback fish live in a certain part of the water. Thus, a gene expression is turned off in the reduced-pelvis stickleback fishes. Because no other genes are turned off, the reduced-pelvis fish can mate with the full pelvis fish despite physiological differences. The two “different” groups still possess the same DNA. It is only due to predation and pressure from that predation that caused such differences in the stickleback fish. Mutations occurred that helped the reduced pelvis stickleback, causing a reduction in the development of the pelvic-fin in the embryo, to serve its biological purpose: to survive and reproduce.