I've been writing some stuff about epigenetics so I've been reading papers on how to define the term [What the heck is epigenetics? ]. Turns out there's no universal definition but I discovered that scientists who write about epigenetics are passionate believers in epigenetics no matter how you define it. Surprisingly (not!), there seems to be a correlation between belief in epigenetics and other misconceptions such as the classic misunderstanding of the Central Dogma of Molecular Biology and rejection of junk DNA [The Extraordinary Human Epigenome]
Here's an illustraton of this correlation from the introduction to a special issue on epigenetics in Philosophical Transactions B.
Ganesan, A. (2018) Epigenetics: the first 25 centuries, Philosophical Transactions B. 373: 20170067. [doi: 10.1098/rstb.2017.0067]
Epigenetics is a natural progression of genetics as it aims to understand how genes and other heritable elements are regulated in eukaryotic organisms. The history of epigenetics is briefly reviewed, together with the key issues in the field today. This themed issue brings together a diverse collection of interdisciplinary reviews and research articles that showcase the tremendous recent advances in epigenetic chemical biology and translational research into epigenetic drug discovery.
In addition to the misconceptions, the text (see below) emphasizes the heritable nature of epigenetic phenomena. This idea of heritablity seems to be a dominant theme among epigenetic believers.
A central dogma became popular in biology that equates life with the sequence DNA → RNA → protein. While the central dogma is fundamentally correct, it is a reductionist statement and clearly there are additional layers of subtlety in ‘how’ it is accomplished. Not surprisingly, the answers have turned out to be far more complex than originally imagined, and we are discovering that the phenotypic diversity of life on Earth is mirrored by an equal diversity of hereditary processes at the molecular level. This lies at the heart of modern day epigenetics, which is classically defined as the study of heritable changes in phenotype that occur without an underlying change in genome sequence. The central dogma's focus on genes obscures the fact that much of the genome does not code for genes and indeed such regions were derogatively lumped together as ‘junk DNA’. In fact, these non-coding regions increase in proportion as we climb up the evolutionary tree and clearly play a critical role in defining what makes us human compared with other species.
At the risk of bearting a dead horse, I'd like to point out that the author is wrong about the Central Dogma and wrong about junk DNA. He's right about the heritablitly of some epigenetic phenomena such as methylation of DNA but that fact has been known for almost five decades and so far it hasn't caused a noticable paradigm shift, unless I missed it [Restriction, Modification, and Epigenetics].
One thing that irks me about the term "epigenetics" is that it confuses two very distinct ideas. The study of of how cells within a multicellular organism inherit their fate and their potency to differentiate into different cell types during development is very much controlled by epigenetic mechanism, no doubt. But inter-generational epigenetic inhritence, which there no doubt exists, seems often overhyped beyond its importance.
ReplyDeleteThere's a nice paper by Deans and Maggert that makes this distinction. They call the first one the "Waddington definition" and the second is the "Holliday definition." They point out that the Waddington definition is useless because we already have a term for that; namely, "regulation of gene expression" and that term covers all sorts of things. They recommend sticking exclusively to the Holliday definition, which they describe as:
Delete"'... the study of phenomena and mechanisms that cause chromosome-bound, heritable, changes to gene expression that are not dependent on changes to DNA sequence.'
We feel that this definition makes a strong distinction between gene regulation (Waddington's definition) and epigenetic inheritance (Holliday's definition), and also emphasizes that epigenetic phenomena must deal exclusively with chromosome-bound changes."
I agree with them [What the heck is epigenetics?]. Mark Ptashne is also not happy about the broad definition because nobody ever called it epigenetics when they were working out the regulation of gene expression in bacteriophage lambda [Core Misconcept: Epigenetics].
Their last sentence: "In fact, these non-coding regions increase in proportion as we climb up the evolutionary tree and clearly play a critical role in defining what makes us human compared with other species." I don't know of data that supports that claim. Actually, there are two claims in there, and neither are true as far as I am aware.
ReplyDeleteThere are three claims in that sentence that are either false or extremely misleading.
Delete1. Noncoding regions increase along any branch leading to humans.
2. There's an evolutionary tree that can be climbed (up) to get to humans.
3. Noncoding regions play a critical role in making us human.
The thing that puzzles me more than anything else is how a competent scientist could still believe those things in the 21st century. The second thing is how could any legitimate scientific journal ever publish something like that.
DeleteWhat it tells me is that these false beliefs are so widespread that nobody thinks to question them.
There is an evolutionary tree, but I think that Ganesan means that what we climb up is a sequence of present-day species. Will it take the remainder of this century to cure people of these delusions? By then will they finally acknowledge that most of the genome's DNA is junk?
Delete3. Noncoding regions play a critical role in making us human.
DeleteWhat's wrong with that one? Presumably, regulatory sequences are important, and they're non-coding. The problem is the claim that an increased number of regulatory sequences are important and that most of the genome consists of regulatory sequences.
I am afraid that it will remain insufficient to point out the shortcomings of individual publications and to question the qualifications of the authors involved.Perhaps one raher needs to examine a complete year of a journal such as Cell, Nature or Science with regard to biological worldviews, sum up common misconceptions about junk DNA and evolutionary theory and publish the results. Unfortunately, the very same journals will likely not accept such papers.
Delete