paramutation in maize and mice

Summary

The video discusses transgenerational epigenetic inheritance, focusing on paramutation-like effects observed in both plants and mice. It explains how epigenetic changes can occur without altering the DNA sequence, using examples from maize and mice with mutations in the kit locus. The script delves into RNA-mediated mechanisms, particularly short interfering RNAs and microRNAs, that may play a role in silencing genes across generations. The lecture highlights the involvement of small RNAs, including piRNAs, and explores their potential to drive epigenetic changes in mammals, suggesting an epigenetic inheritance pathway that might also apply to humans.

Takeaways

• 😀 Paramutation is a phenomenon where one allele silences another allele of the same genetic identity in a trans manner, and was first observed in maize plants by Royal Alexander Brink in the 1950s.
• 😀 In maize, the purple stem or husk color is controlled by a transcription factor called B1, which is regulated by upstream tandem repeats that can either be active or inactive.
• 😀 In plants, paramutation occurs when a heterozygote with one active and one inactive allele experiences crosstalk between the alleles, leading to silencing of the inactive allele.
• 😀 Small RNA molecules, specifically 24 nucleotide small interfering RNAs (siRNAs), are involved in mediating paramutation in plants by directing RNA-mediated DNA methylation.
• 😀 Paramutation-like effects have been observed in mice, specifically at the kit locus, where a transgene insertion leads to a mutant allele causing pigmentation issues in mice.
• 😀 The kit locus in mice is crucial for melanocyte migration, and mutations in this gene can result in white spotted patches on the mouse's coat, which is similar to the observed phenotype in border collies and other dogs.
• 😀 A transgenerational inheritance pattern for the kit mutation was observed, where offspring showed a higher percentage of white-spotted phenotypes than expected based on Mendelian inheritance.
• 😀 Interestingly, while the genetic inheritance followed expected patterns, the phenotype of some wild-type offspring was still influenced by the paramutated kit allele from the previous generation.
• 😀 Researchers hypothesized that RNA might be mediating the paramutation-like effect, and experiments with microinjections of RNA from white-spotted mice into wild-type mouse oocytes demonstrated that RNA could transmit the phenotype.
• 😀 RNA molecules such as microRNAs or piRNAs may play a role in transgenerational epigenetic inheritance, as demonstrated by the microRNA-mediated effects in the kit locus, although the exact mechanisms remain unclear.

Q & A

What is paramutation, and where was it first described?

Paramutation is a process in which one allele can silence another allele in a trans manner without changing the underlying DNA sequence. It was first described in maize by Royal Alexander Brink in the 1950s.

How does paramutation occur in plants?

In plants, paramutation occurs when one allele (e.g., B1) is active and expresses a trait, while another allele (e.g., B1') is epigenetically silenced. When these alleles are in a heterozygous state, the active allele can silence the inactive allele through a process mediated by small RNA molecules, leading to an epigenetic change.

What role do small RNAs play in the paramutation process in plants?

Small RNAs, particularly 24-nucleotide small interfering RNAs (siRNAs), are produced from tandem repeats in plants. These small RNAs mediate RNA-directed DNA methylation, leading to the silencing of the allele in trans, thus causing the paramutation effect.

How is the concept of paramutation observed in mice?

In mice, a paramutation-like effect has been observed at the Kit locus. A transgene insertion at this locus leads to decreased Kit expression, resulting in a white-spotted phenotype. When this mutant allele is inherited, it can cause a similar phenotype in offspring, even if the offspring are genetically wild-type for the Kit locus.

What phenotype results from the Kit mutation in mice?

The Kit mutation in mice leads to a white-spotted phenotype, with the most noticeable white patches on the belly, feet, and tail. This is due to a lack of proper melanocyte migration during development, which is caused by reduced Kit protein expression.

How does inheritance work in the case of the Kit mutation in mice?

When a mutant Kit allele is inherited, approximately 90% of the offspring show the white-spotted phenotype, regardless of whether the allele is inherited from the mother or father. This is more than the 50% expected by genetic inheritance, suggesting an epigenetic effect influencing the phenotype.

What is the genetic status of mice with a white-spotted phenotype in the Kit mutation study?

Mice with a white-spotted phenotype are genetically wild-type for the Kit locus, meaning they do not have any mutations in the DNA sequence of Kit. However, they exhibit the mutant phenotype due to a paramutation-like effect, which involves epigenetic changes.

How do researchers suggest that RNA might be mediating transgenerational inheritance in the Kit mutation model?

Researchers suggest that RNA may be mediating the transgenerational inheritance of the Kit mutation phenotype. They observed that injecting RNA from the testis or somatic cells of a white-spotted mouse into a fertilized egg resulted in genetically wild-type offspring exhibiting the same phenotype, supporting the idea of RNA involvement in this effect.

What types of RNA are implicated in the transgenerational effects seen in the Kit mutation study?

The study suggests that small RNAs, including microRNAs and piRNAs, may play a role in the transgenerational epigenetic inheritance observed in the Kit mutation model. These RNA species could influence gene expression without changing the DNA sequence.

What is the significance of piRNAs in the context of the Kit mutation and epigenetic inheritance?

PiRNAs are small RNAs that are involved in RNA-directed DNA methylation, which is a mechanism known to mediate epigenetic changes. In the context of the Kit mutation, piRNAs may contribute to the transgenerational inheritance of the mutant phenotype, as they are expressed during spermatogenesis and are crucial for fertility.