Monday, 13 November 2023
The epigenome:The kingmaker?
Epigenetics: Performing the Genome
Epigenetics has been rising in esteem contemporaneously with the decline of the Central Dogma of genetics (that DNA is the master control in the cell). Just as the pianist gets the applause and not the piano, the epigenome is now being considered the artist behind the instrument. It’s not that the genome has lost any of its aura, but it cannot do anything without a performer.
Frank Gannon wrote a most interesting essay in the journal EMBO Reports, titled, “The piano and the pianist.” Gannon, an Australian who was the former director of a medical research institute in Brisbane, was not writing about the performing arts. He wanted to introduce a new analogy to overcome “the ubiquitous ‘DNA is the blueprint of life’ interpretation of biology,” repeated by some who downplay the elements in the cell that give an organism its dynamic responsiveness to the environment.
The image of inevitability and of a rigorous design plan, and the notion of the dominating importance of DNA are misleading messages, however, that do not represent reality.
I suggest that the piano and the pianist is a better analogy as to how our lives and our health unfold.
Gannon denies that our health is genetically determined: i.e., if we have a certain genetic defect, we will get the disease. That is not entirely true, he says as he details the analogy.
The function of each piano is defined by its 88 keys, but different pianos have different tones and timbres.Some pianos have defects that distort some notes. These could be at the little-used periphery of the keyboard or they could be more central. If the middle C was out of tune, it could be very jarring for the listener in a solo lyrical piece but it may be more subtle if it is part of complex chords. More importantly, though, it is the way the pianist plays the piano that will define the outcome as a pleasure or as discordant. Each pianist selects the tempo and the mood and may even compensate for a dud note.
How Does the Analogy Relate to Biology?
Writes Gannon, “If the keyboard is the genetic code, the piano is the epigenetic context that interprets the blueprint of life and varies the outcome.” He discusses specific ways cells “perform” the genome. DNA is wrapped in chromatin made of histone proteins that can be tagged with markers like methyl or acetyl groups. Parts can be phosphorylated or tagged with ubiquitin proteins. A host of accessory proteins switch genes on and off, responding to cues from the environment. Indeed, “a growing number of regulatory RNAs create a bewildering combination of possibilities that define the performance of the cell and ultimately of the individual.”
No analogy is perfect, and one must understand that most of these regulatory agents are coded in DNA themselves. In music, we don’t see pianists emerging from the keys of a piano. Still, the “defining role of epigenetics” deserves more attention, Gannon argues. We are not slaves of our genes. Lifestyle choices, such as diet, exercise, and mental habits, can improve the quality of the performances played on our genetic instruments.
Most of Gannon’s one-page essay deals with epigenetic targets for treating genetic diseases. While surprised at the lack of attention given to epigenetics, he understands the difficulties involved. “Compared to the neat linearity of the genome,” he notes, “epigenetic regulation is a mess that is hard to reduce into a defined sequence.” Targeting the correct epigenetic regulator is correspondingly difficult. If the dud note is middle C, a carelessly targeted drug might inadvertently put a different note out of tune.
In biology, additional factors other than the genome and epigenome come into play, such as the microbiome — all those microbial and viral partners in and on the organism. These, in turn, respond to the habits of the organism in its habitat. Gannon ends with a cadenza and coda:
As we analyze the beneficial effects of a healthy microbiome and lifestyle, we are looking for answers to why these work. What does the microbiome in the gut provide the organism with to improve health? What are the molecular consequences of exercise such that the total organism and not just the muscles work better? How does diet modify the health of individuals? How does excess fat impact functions in other tissues? More results and more insights will inevitably highlight the crucial role of the epigenome as the connection between the environment and the genome. The piano remains important, but the pianist will finally move into the limelight.
Other Epigenetic News
Researchers at the John Innes Centre explored “intricate mechanisms of epigenetic silencing” (the suppression of gene activity) that impact vernalization in plants. Researchers identified several accessory proteins that trigger epigenetic switches when Arabidopsis plants feel the cold snap that indicates the time for flowering is coming. The switch turns off the floral repressor gene FLC, allowing the genes for bud formation to activate.
At the University of Georgia, researchers investigated the ticking of epigenetic clocks that are biomarkers for aging. “While these clocks work accurately from birth until death,” the press release says, “they are set back to zero in each new generation.” The team confirmed that such epigenetic clocks work in plants, including Arabidopsis and poplar trees, and that these clocks “keep ticking accurately over many generations.”
Remember “Intelligent Design at High Altitudes”? Another paper in Current Biology examined genetic changes in 2,252 Tibetan women who live at high elevations. The authors claim the gene modifications show evidence of positive natural selection. It appears though, that instead of finding new adaptive genes, they found existing genes that were downregulated — i.e., epigenetic responses to the low oxygen atmosphere rather than naturally selected mutations.
Putting Life Back into Performance
Gannon’s piano analogy suggests opportunities for design theorists. If the genome is like the piano keyboard, it cannot be that the epigenome is as static and determined as the sheet music on the stand. There is dynamic responsiveness in the performance. The pianist (if by that we mean the organism) might have to play the same piece as another individual within its species, but can alter the tempo and quality of the performance depending on the occasion: the audience, the venue, the number of broken keys, the amount of stress on the player, the player’s age and experience, and other factors.
Every zebra, zebra finch, or zebrafish may resemble its conspecifics, but no two individuals will follow the exact same path. A plains zebra in South Africa may face fewer predators than one in the Serengeti but will endure wider swings in seasonal temperatures. Many individual organisms, such as snowshoe hares, change their appearance from summer to winter. Deciduous trees cycling through seasonal changes offer another example. Epigenetic responses in different tissues of the body will also behave according to local conditions despite having the same genome. The epigenome tunes each performance using its built-in mechanisms to detect the conditions in the environment. It switches on internal controls that adapt cell processes appropriately to the conditions they are sensing. Design theorists are keen on elucidating the mechanisms by which organisms track the environment and actively switch on applicable responses.
Beyond Histones
If epigenetics plays the genome, who plays the epigenome? What tells the epigenome to add a methyl group to a particular histone on a particular gene? Is epigenetics just another layer of information written in matter, cycling mindlessly, amenable to philosophical naturalism? What breathes fire into a piano piece, putting the soul into a rendition by Van Cliburn or Vladimir Horowitz? Even a paper roll with dots on it, running through a mechanical player piano, had to be originally performed by a live pianist. The same is true with digital recording: the soul of the performance is not in the bumps on a CD or the bits in an MP3 file.
If scientists were ever to put together all the parts of a cell, I’m not convinced it would come alive. Information by itself is sterile. All the codes and epi-codes for all the parts could be present, but they would exist as mere fancy arrangements of dumb matter without an additional spark. A spark-discharge apparatus wouldn’t do it. Dr. Frankenstein’s Tesla-coil bolts wouldn’t make his monster sit up except in the movies. To be or not to be is a metaphysical question, but the animating factor that switches on life itself — whether in microbe or man — appears to be an endowment from the ultimate Mind
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