Is epigenetics one of the best ideas of the 21st century?

New Scientist has produced a special issue on the best ideas of the 21st century. Here's the complete list.

• Microbiome: The hidden microscopic ecosystem shaping our health
• Neurodiversity: The revolutionary realisation that there's no such thing as a "typical" brain
• Our new family tree: The unexpectedly epic saga of our species Homo sapiens and its predecessors
• Our solar system is weird: The revelations that the cosmos is mostly very different from our strange little corner of it
• Transformer architecture: The common foundation of today's AI giants
• Net zero:The surprising moment that changed the whole planet’s approach to climate change
• What should we eat?: Time and time again, scientists have found one diet beats all others when it comes to our health
• Smartphones: A computer in every person’s pocket – why the pros outweigh the cons
• Transient astronomy: Watching the universe’s biggest dramas in real time
• Epigenetics: How your surprisingly simple genome builds an extraordinarily complex you
• Embracing quatnum weirdness: Albert Einstein doubted quantum theory – but accepting its strangeness has led to great things
• Gigafactories: The unprecedented step towards electrifying everything
• Climae attribution studies: A groundbreaking technique that brings the devastating consequences of climate change home
• Brain meworks: The eureka discovery that revealed the origins of our most complex thought processes
• CRISPR: We finally have the power to edit our own genetic code
• Click chemistry: A powerful new technique for making the stuff of life
• Wikipedia: The world’s most surprising and essential hub of knowledge
• Landscape of fear: How predators drastically shape ecosystems – in ways we’d never predicted
• 1.5°C: The unlikely target that transformed global climate ambitions
• End-to-end encryption: A wall that keeps our digital secrets safe
• Managing HIV: The game-changing preventative drugs that have benefitted millions

To me, this list says a lot about the poor quality of today's science writers.¹ I'll pick just one as an example.

The hidden power of epigenetics: Best ideas of the century
Following the surprising discovery that our genetic blueprint is much simpler than expected, we’ve rapidly learned that we have epigenetics to thank for our extraordinary complexity
by Colin Barras

The article begins with the common false history of the number of genes in the human genome.

At the dawn of the millennium, the number of genes in our genome was still up for discussion. When we finally got our first official estimate, the number was so far below expectations that it helped turbocharge a movement to rethink the evolutionary process.

In 2001, the Human Genome Project announced we have no more than 40,000 protein-coding genes – a figure that has since been revised down to about 20,000. We needed other mechanisms to explain the complexity of our biology and evolution. It was epigenetics’ time to shine.

Epigenetics is a catch-all term to describe how a wide variety of molecules interact with DNA or RNA to influence the activity of genes without changing the underlying genetic code. Two cells with identical genomes but different epigenetic markers can look and behave very differently.

... those ignorant of history are not condemned to repeat it; they are merely destined to be confused.

Stephen Jay Gould
Ontogeny and Phylogeny (1977)

Sandwalk readers will be familiar with this story. When the human genome sequence was published there were lots of scientists and science writers who had not kept up with the scientific literature on the number of genes in the human genome. The knowledgeable experts had been predicting about 30,000 genes based on evidence dating back to the late 1960s. It was no surprise to them that their predictions turned out to be correct. [Hisorical estimates of the number of genes]

The result was a surprise to scientists and science writers who were expecting many more genes based largely on their ignorance of the scientific literature. They assumed that humans must have lots of genes because humans are so complex.

Under normal circumstances, when a scientific result doesn't conform to your expectations it's time to reevaluate your assumptions. That didn't happen. These surprised scientists and science writers didn't delve into the literature to find out why the knowledgeable experts were correct or why their assumptions might have been flawed. Instead, they tried to rescue their beliefs by coming up with multiple explanations for why we could still be the most complex species even if we had the same number of genes as "lower" species.

The explanations included alternative splicing, non-coding genes, complex regulation, transposons, pseudogenes, and epigenetics. All of these excuses explanations are designed to account for the missing compexity that's supposed to distinguish humans from all other species.

This is the Deflated Ego Problem and their form of argument is a fallacy known as Ad Hoc Rescue The fallacy is described by Chris DiCarlo in his book on critical thinking.²

Ad Hoc Rescue
The term ad hoc is Latin and literally means “for this purpose.” It involves the addition of more premises in an attempt to save a particular belief or position. By itself, adding more propositions is not fallacious. It becomes fallacious, however, when one’s new propositions do not possess convincing evidence but merely reflect a person’s biased ties to the cherished belief of position.

Epigenetics is a fancy word for regulation of gene expression. It is not a 21st century idea. It's been around since the 1960s (>60 years). The most common form of regulation is at the level of transcription initiation and that's controlled by the binding of transcription factors near the transcription start site. These transcription factors may be activators or repressors.

This basic level of control is augmented in eukaryotes by changes in chromatin structure. There are basically two forms of chromatin: a tightly packed form of nucleosomes called a "closed domain" and a more open form called an "open domain" [Open and closed chromatin domains (and epigenetics)]. The shift from one form to the other is aided by the methylation (closed domain) or demethylation (open domain) of DNA and by modifications of the histone molecules in the nucleosomes.

These changes (demethylation and histone modification) are triggered by the binding of transcription factors that lead to activation of a nearby gene. It's important to note that changes in methylation and histone modification are almost always consequences of transcription factor binding and not causes of regulation. It is the transcription factors that recognize specific DNA sequences leading to activation of certain genes.³

The thing that nature figured out—it’s kind of amazing, actually—is that once you have all the reading machinery, it’s just a question of recruiting it to the right place. And to do that we have evolved these very simple little factors that get together and attract the RNA polymerase to the gene.

This is a quotation from Kat Arney's interview with Mark Ptashne in her book Herding Hemingway's Cats (p.58). Ptashne is referring to his "recruitment model" (Ptashne and Gann, 1997; Ptashne, 2013) and what he means is that the E. coli and bacteriophage model is probably (mostly) true of eukaryotes as well. Support for the recruitment model is a way of fighting back against the hype of chromatin changes and "epigenetics" (whatever that is) and against the idea that post-transcriptional mechanisms of regulation such as alternative splicing, RNA degradation, and translational control by regulatory RNAs play a significant role in controlling the concentration of proteins in a eukaryotic cell.

• Protein concentrations in E. coli are mostly controlled at the level of transcription initiation
• New Scientist promotes misinformation about evolution
• What do believers in epigenetics think about junk DNA?
• What the heck is epigenetics?
• Core Misconcept: Epigenetics
• Calico Cats

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1. I'm surprised that mRNA vaccines didn't make the list.

2. DiCarlo, C. (2011) How to Become a Really Good Pain in the Ass: A Critical Thinker's Guide to Asking the Right Questions, Prometheus Books, Amhurst, New York, USA (p. 128)

3. See the link to calico cats as an exception that proves the rule.

p>Ptashne, M. and Gann, A. (1997) Transcriptional activation by recruitment. Nature 386:569-577. [doi: 10.1038/386569a0]

Ptashne, M. (2013) Epigenetics: core misconcept. Proceedings of the National Academy of Sciences (USA) 110:7101-7103. [doi: 10.1073/pnas.1305399110]