Paramutation

In epigenetics, paramutation is an interaction between two alleles of a single locus, resulting in a heritable change of one allele that is induced by the other allele. Paramutation violates Mendel’s first law, which states that in the process of the formation of the gametes (egg or sperm) the allelic pairs separate, one going to each gamete, and that each allele remains completely uninfluenced by the other. In paramutation an allele in one generation heritably affects the other allele in future generations, even if the allele causing the change is itself not transmitted. What may be transmitted are patterns of DNA methylation or RNAs such as piRNAs, siRNAs, miRNAs or other regulatory RNAs. Through proper breeding, paramutation can result in isogenic sibling plants with drastically different phenotypes.

Paramutation was first discovered and studied in maize (Zea mays) by R.A. Brink at the University of Wisconsin–Madison in the 1950s. Brink noticed that specific weakly expressed alleles of the red1 (r1) locus in maize, which encodes a transcription factor that confers red pigment to corn kernels, can heritably change specific strongly expressed alleles to a weaker expression state. The weaker expression state adopted by the changed allele is heritable and can, in turn, change the expression state of other active alleles in a process termed secondary paramutation. Brink showed that the influence of the paramutagenic allele could persist for many generations.

Interestingly, paramutation can result in a single allele of a gene controlling a spectrum of phenotypes. At r1 in maize, for example, the weaker expression state adopted by an allele following paramutation can range from completely colorless to nearly fully colored kernels. This is an exception to the general observation that continuous variation is controlled by many genes.

Allelic interactions similar to paramutation have since been reported in other organisms, including tomato, pea, and mice.

The molecular basis of paramutation is being unraveled, almost exclusively in maize. Paramutation may share common mechanisms with other epigenetic phenomena, such as gene silencing and genomic imprinting. In maize, paramutation seems to share many traits with the well understood RNA-directed DNA-methylation pathway in Arabidopsis thaliana, even though it has never been observed in the famous model plant. Alleman (2006) reported that, in maize, "paramutation is RNA-directed. Stability of the chromatin states associated with paramutation and transposon silencing requires the mop1 gene, which encodes an RNA-dependent RNA polymerase." Exactly how the RNA produced by this polymerase causes paramutation in maize is not yet understood, but like other epigenetic changes, it involves the covalent modification of DNA and/or the DNA-bound histone proteins without changing the DNA sequence itself.

EXPLANATION

A classic example of natural TGS, called paramutation, occurs when certain combinations of alleles are present together in heterozygous conditions. Paramutation was first described in maize for the r1 (Red1) gene and later was shown to occur for two other maize genes, b1 (Booster and pl1 (Purple plant, each of which encode transcriptional regulators of anthocyanin biosynthesis. Paramutation produces a heritable change in the expression state of the affected allele, resulting in reduced tissue pigmentation. Paramutation of b1 and pl1 was correlated with reduced transcription of the affected genes, without any detectable changes in their primary DNA sequence. In addition to these natural paramutation phenomena in maize, certain transgene loci in petunia, tobacco, and rice are reported to interact in a manner similar to that seen in paramutation. These results indicate that trans-silencing effects resulting from homology-based interactions similar to paramutation are likely to be widespread in plant . A violation of one of Mendelian genetics' central rules—that in a heterozygote, one allele does not alter in any way or influence the expression of the other allele—is seen in paramutation. In maize, several loci that encode regulators of the anthocyanin synthesis pathway [red1 (r1), booster1 (b1) and purple plant1 (pl1)] show paramutation interactions between their different respective alleles, Three classes of alleles occur in paramutation: paramutagenic, paramutable and neutral. In a heterozygote, paramutagenic alleles are able to convert paramutable alleles to a paramutagenic allele, which is seen as a huge drop in expression from the converted allele. Not only does this conversion persist in the heterozygote and result in highly reduced expression of the locus, but the alteration to the paramutable allele is heritable. Hence, the modified, silenced allele can be segregated away from the original paramutagenic allele, and it can then persist and behave as a paramutagenic allele itself and convert other natïve paramutable alleles. Typically, this new state is stable but it can convert back spontaneously to the naïve paramutable state Of course, this indicates that the alteration is not at the nucleotide level and indeed this has been demonstrated to be the case in paramutation. Although paramutation was originally discovered in maize, several examples of paramutation in other plants have been discovered, overlapping with transgene silencing in some cases, although it remains rare and exceptional

References

• BBC Science News - An easy to understand article involving paramutation
• Hollick JB, Dorweiler JE, Chandler VL (August 1997). "Paramutation and related allelic interactions" (Review). Trends Genet. 13 (8): 302–8. doi:10.1016/S0168-9525(97)01184-0. PMID 9260515. http://linkinghub.elsevier.com/retrieve/pii/S0168952597011840. 
• Alleman M, Sidorenko L, McGinnis K, et al. (July 2006). "An RNA-dependent RNA polymerase is required for paramutation in maize". Nature 442 (7100): 295–8. doi:10.1038/nature04884. PMID 16855589. 
• Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F (May 2006). "RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse". Nature 441 (7092): 469–74. doi:10.1038/nature04674. PMID 16724059. 
• Chandler VL, Stam M (July 2004). "Chromatin conversations: mechanisms and implications of paramutation" (Review). Nat. Rev. Genet. 5 (7): 532–44. doi:10.1038/nrg1378. PMID 15211355. 
• Stam M, Mittelsten Scheid O (June 2005). "Paramutation: an encounter leaving a lasting impression". Trends Plant Sci. 10 (6): 283–90. doi:10.1016/j.tplants.2005.04.009. PMID 15949762. http://linkinghub.elsevier.com/retrieve/pii/S1360-1385(05)00104-4.