Genome complexity: controlling gene silencing (Introduction)

by David Turell , Friday, March 08, 2024, 20:26 (259 days ago) @ David Turell

Special epigenetic marks are part of the process:

https://www.sciencedaily.com/releases/2024/03/240306150553.htm

"The Burga Lab at the Institute of Molecular Biotechnology...uncovered a novel gene regulation process, associated with the silencing of selfish genes, that could represent the first step in the evolution of imprinting. Their discovery, reported in Nature, could begin to solve the mystery of how and why imprinting first evolved. 

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"In diploid organisms, one set of chromosomes is inherited from each parent. However, not all of the genes contained within will be expressed equally; instead, some may be silenced depending on whether they were inherited from the mother or the father. This phenomenon, known as genomic imprinting, depends on DNA methylation, an epigenetic signal that is erased and rewritten in every generation. Genomic imprinting arose independently in mammals and plants over 100 million years ago. However, how this mechanism evolved has, so far, remained largely a mystery.

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"Pliota was investigating toxin-antidote elements (TAs), a type of selfish element that has evolved a fascinating mechanism to ensure its own inheritance: When a mother carries the TA, it will "poison" its eggs with a toxin that can only be countered by an antidote which is also present in the TA," she explains, "this way, all descendants that don't inherit the TA will either die or be developmentally delayed. 

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"To figure out the mechanism of the observed parent-of-origin effect, the Burga group decided to study the main germline defense mechanism against selfish genetic elements, known as the piRNA pathway. In the piRNA pathway, a coordinated effort of different small RNA molecules and proteins silences the expression of selfish elements during germline development to ensure genome stability in reproduction. 

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"They proved that, in maternal inheritance, the TA is accompanied by the toxin mRNA, which is expressed in the germline of the mother and loaded into the egg. The Burga group showed that this mRNA marks the TA as "own," avoiding its silencing by the piRNA pathway. This process is called epigenetic licensing, and its balance with the piRNA pathway determines whether a gene is expressed or not. 

"On the other hand, when the TA is inherited paternally, the lack of maternal mRNA means there is no licensing, leading to a strong repression of the toxin gene and very low levels of toxin being expressed. By default, the piRNA pathway will silence the toxin gene explains Burga. Unless there's maternal mRNA that licenses it by repressing the piRNA pathway. This inhibition of the inhibitor is what causes the toxin gene to be active, and the eggs to be poisoned. 

"Interestingly, this silencing pattern was observed to last for several generations, meaning that lack of licensing in one generation can even affect their great-grand-daughters. This is not the case in genomic imprinting, which gets reset in each generation. 

"The results from the Burga group cement the evolutionary link between parent-specific gene expression and host defence mechanisms, tracing the origins back to organisms that lack DNA methylation and canonical imprinting. Despite the differences between these processes in worms and mammals, the Burga group believes that the mechanism they described could represent an evolutionary first step for more advanced forms of inherited silencing. These more advanced forms of silencing ended up regulating the expression of the cell's endogenous genes, leading to the evolution of genomic imprinting."

Comment: this genome process is highly complex requiring very exact proteins to act in the rles they do. How did a chance evolutionary process find them among the morass of possible protein forms that might exist or be made to esist? Not by chance!