Monday, June 30, 2008

Genome Communication: Alleles Of Homologous Genes Can Silence One Another

[Source: ScienceDaily] - In the late 19th century Gregor Mendel used peas to show that one copy of a gene (allele) is inherited from the mother and one from the father. In the progeny, the inherited genes are expressed at the right time and in the right place, but until recently, it was thought that although gene products could be modified during the life of the organism, the genes themselves were unchanged, except for random mutation.

Now it appears that one copy of some genes can alter the expression of the other copy, and those changes are passed down to the next generation. These epigenetic alterations, called paramutations may be important in introducing changes when plants and other organisms are environmentally stressed. The exact mechanisms of how genes talk to other genes and change their behavior are being investigated, and recent results suggest that these processes could be important in engineering plants responsive to a variety of environmental conditions.

Dr. Vicki Chandler and her colleagues have studied paramutations in maize and other plants and have identified some of the genes and mechanisms that operate in this epigenetic process. Dr. Chandler, of the Department of Plant Sciences at the University of Arizona, Tucson, will be presenting this work at a symposium on Maize Biology at the annual meeting of the American Society of Plant Biologists in Mérida, Mexico (June 28, 9:10 AM).

The sequencing of genes, proteins, and, ultimately, whole genomes has revealed that genomes are not simply strings of genes, but rather complex, communicating, and interacting regions of information that could be compared to DNA computers controlling growth, development, and metabolism in each organism. The physical architecture of the genome is also highly complex.
The nucleus, where the genome resides, is not full of strings of DNA like a pot of spaghetti.

Rather, the strands of DNA are wrapped around proteins called histones and the whole is organized into an elegant and highly controlled structure called chromatin. When it is time for genes to be expressed, a section of chromatin is unwound and the DNA for that particular gene is made available to the machinery that transcribes DNA to RNA. Once the process is finished, the DNA is neatly folded back into the chromatin structure until needed again.

Different parts of the genome can interact by direct contact or through intermediaries that can be proteins or RNA sequences. The exact mechanisms of how paramutagenic alleles communicate with their homologous partners are still unknown, but the work of Chandler and others suggests that both direct contact of homologous regions and changes induced by intermediary RNA molecules may be involved.

Peas also played an important role in the discovery of paramutations, as the first mutants of this type were observed in peas in 1915. Then, in the 1950s, Alexander Brink identified these types of mutations as interactions between alleles. He recognized that these interactions resulted in heritable changes to the expression of those genes. Since then, paramutations have been found in humans and other animals, as well as other plant species including tomato, tobacco, petunia, and maize. In animals, paramutations may be important in mediating the occurrence of diseases like diabetes. Chandler and her co-workers have been investigating paramutations in maize at the b1 gene, which regulates the distribution of the purple pigment anthocyanin in plant tissues.

At the b1 locus, the paramutagenic allele, which causes light or stippled pigmentation arises spontaneously from the wild-type allele, which causes dark purple pigmentation. If a plant with the paramutagenic allele is crossed with a wild-type allele, the progeny get both alleles. However, the paramutagenic allele silences the wild-type allele and produces a plant with stippled rather than purple pigmentation. The silent state is then passed on in subsequent crosses.

Several different components may be involved in paramutation, although they may differ among species. One important player is an array of repeated non-coding DNA sequences that lies upstream of the gene sequence of the paramutagenic allele. Seven of these tandem repeats are required for b1 paramutation. If only three tandem repeats are present, there is only partial paramutagenic activity. One possibility is that these tandem repeats are involved in direct interactions of chromatin regions, which results in paramutation changes.

However, RNA also appears to be part of the process. The gene mediator of paramutation1 (mop1), an RNA dependent RNA polymerase is absolutely required for paramutation silencing at the b1 locus as well as for several other maize genes. In Arabidopsis, this RNA polymerase is associated with the production of small, interfering RNAs (siRNA) that function in gene silencing in other contexts. The siRNA could thus act as an intermediary molecule, being sent to silence the homologous allele. A third component is the placement of methyl groups on the control sequence (promoter) of the wild-type gene.

Gene methylation has been known for some time as a cell defense mechanism for silencing foreign DNA but is also functional in other cellular processes. In several species, such methylation is also directed by RNA molecules. None of these processes is likely to be sufficient by themselves to effect paramutation, but rather all of them may interact, although to varying degrees in different species.

The molecular components of paramutation probably arose as cell defense mechanisms against viral or bacterial DNA. They have evolved to serve the needs of plants that grow in complex and changing environments from which they cannot escape, but to which they may be able to adapt through mechanisms like paramutation. Indeed, two instances of paramutation are known to be influenced by temperature. This work has implications for engineering crops that may be able to adapt to higher temperatures or drought conditions, as well as for applications in human and veterinary medicine.

Adapted from materials provided by American Society of Plant Biologists, via EurekAlert!, a service of AAAS.

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