Paramutation
Genetic phenomenon involving heritable changes in gene expression
Paramutation is a genetic phenomenon that results in a heritable change in the expression of a gene without altering the DNA sequence. This process involves an interaction between two alleles of a single gene, where one allele induces a heritable change in the other allele. Paramutation is a form of epigenetic inheritance, as it involves changes in gene expression that are not due to changes in the underlying DNA sequence.
Mechanism
Paramutation involves a complex interplay of RNA molecules, DNA methylation, and chromatin modifications. The process typically requires the presence of specific non-coding RNAs that guide the modification of chromatin structure, leading to altered gene expression. These changes can be stably inherited through mitosis and sometimes through meiosis, affecting subsequent generations.
RNA-Mediated Silencing
In many cases, paramutation is mediated by small interfering RNAs (siRNAs) or microRNAs (miRNAs) that target specific gene sequences. These RNA molecules can recruit protein complexes that modify histones or methylate DNA, leading to a repressed state of the gene.
Chromatin Modifications
Paramutation often involves changes in the chromatin state of the affected gene. This can include the addition of methyl groups to histone proteins or to the DNA itself, which can alter the accessibility of the gene to the transcriptional machinery. These modifications can be maintained through cell division, allowing the paramutated state to be inherited.
Examples in Nature
Paramutation has been observed in several plant species, including maize and tomato. In maize, the best-studied example involves the b1 locus, where one allele can silence another allele in a heritable manner. This phenomenon has also been observed in some animal systems, although it is less well understood.
Maize
In maize, paramutation at the b1 locus involves the interaction between two alleles, B-I and B: the B-I allele is highly expressed, while the B allele is not. When these alleles are present in the same plant, the B-I allele can be converted to a B-like state, resulting in reduced expression. This change is stable and can be passed on to the next generation.
Tomato
In tomato, paramutation has been observed at the Colorless non-ripening (Cnr) locus, where the presence of a paramutagenic allele can lead to a heritable change in fruit ripening characteristics.
Significance
Paramutation challenges the traditional Mendelian inheritance model by demonstrating that alleles can influence each other in a non-Mendelian manner. This has significant implications for our understanding of genetic regulation and epigenetics. It also raises questions about the stability of genetic information and the potential for epigenetic variation to contribute to evolution.
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Contributors: Prab R. Tumpati, MD