Thursday, November 23, 2023

Against "Junk DNA"


Newly Published Paper in BioEssays Recognizes Kuhnian “Paradigm Shift” Against Junk DNA

Casey Luskin

November 22, 2023, 7:44 AM

 September, I wrote about prolific functions discovered for short tandem repeats (STRs), formerly considered a type of “junk DNA.” Now a newly published paper in BioEssays has strongly rebuffed the idea of junk DNA — using the language of Kuhnian paradigm shifts. Before we go any further, let’s review just what a Kuhnian paradigm shift is.

The phrase comes from the work of a famous Harvard University historian and philosopher of science, Thomas Kuhn. In his influential book The Structure of Scientific Revolutions, he documented how new ideas in science typically take hold through what are called “paradigm shifts,” where the leading framework within a field (the “paradigm”) starts to accrue evidential problems (goes into “crisis”) until it finally gives way to a new idea that challenges the status quo. Kuhn further showed that most scientists spend most of their time doing “normal science” — basically solving scientific puzzles within the framework of the dominant paradigm. He observed that the scientists of the old guard paradigm are “often intolerant” of “new theories” that are being proposed by new scientists proposing ideas that challenge the reigning paradigm. A new theory “emerges first in the mind of one or a few individuals” but then it spreads because the field faces “crisis-provoking problems,” especially among scientists who are “so young or so new to the crisis-ridden field that practice has committed them less deeply than most of their contemporaries to the world view and rules determined by the old paradigm.”

A Junk DNA Paradigm Shift

This brings us to the article recently published in BioEssays, written by John Mattick, an Australian molecular biologist and Professor of RNA Biology at the University of New South Wales, Sydney. I have no evidence that Mattick has any affinities with intelligent design — but he’s a prime example of a bold scientist who has embraced new theories that challenge the reigning paradigm. Mattick has been indefatigable in following the evidence where it leads regarding evidence of function for “junk DNA.” In part because of his work, biology today has experienced a paradigm shift away from the concept of junk DNA. In fact, Mattick’s new BioEssays article, “A Kuhnian revolution in molecular biology: Most genes in complex organisms express regulatory RNAs,” frames the revolution in thinking over junk DNA precisely in “Kuhnian paradigm shift” terms. The paper has a nice video abstract, but here’s what it says in written form: 

Thomas Kuhn described the progress of science as comprising occasional paradigm shifts separated by interludes of ‘normal science’. The paradigm that has held sway since the inception of molecular biology is that genes (mainly) encode proteins. In parallel, theoreticians posited that mutation is random, inferred that most of the genome in complex organisms is non-functional, and asserted that somatic information is not communicated to the germline. However, many anomalies appeared, particularly in plants and animals: the strange genetic phenomena of paramutation and transvection; introns; repetitive sequences; a complex epigenome; lack of scaling of (protein-coding) genes and increase in ‘noncoding’ sequences with developmental complexity; genetic loci termed ‘enhancers’ that control spatiotemporal gene expression patterns during development; and a plethora of ‘intergenic’, overlapping, antisense and intronic transcripts. These observations suggest that the original conception of genetic information was deficient and that most genes in complex organisms specify regulatory RNAs, some of which convey intergenerational information.

Mattick describes the previously reigning “junk DNA” paradigm in biology as having come from “prevailing assumptions.” The assumptions hold that “‘genes’ encode proteins, that genetic information is transacted and regulated by proteins, and that there is no heritable communication between somatic and germ cells.” This view that genes encode proteins is a key part of the “central dogma” of biology. Of course, no one denies that genes encode proteins — Mattick’s point is that they can do much more than this. They can also encode RNAs and the evidence shows that many non-protein-coding sequences of DNA actually encode RNAs that perform many types of vital functions in the cell. 

Junk DNA and Evolution

So the central dogma of molecular biology is part of what is perpetuating the idea that if a stretch of DNA doesn’t encode a protein then it isn’t doing anything and is “junk.” But there’s another major driver of the failing junk DNA paradigm in biology — and it stems directly from evolutionary thinking. Mattick explains:  

[T]heoretical biologists were integrating Mendelian genetics with Darwinian evolution, leading in 1942 to the so-called Modern Synthesis, which made two primary claims: mutations are random and somatic mutations are not inherited. … In 1968 Kimura proposed the neutral theory of molecular evolution, which posited that “an appreciable fraction” of the genome was evolving independently of natural selection. In 1969, Nei concluded that, given the “high probability of accumulating … lethal mutations in duplicated genomes … it is to be expected that higher organisms carry a considerable number of nonfunctional genes (nonsense DNA) in their genome”, leading Ohno to promote the concept of “junk DNA”, also arguing that “in order not to be burdened with an unbearable mutation load, the necessary increase in the number of regulatory systems had to be compensated by simplification of each regulatory system”. [Emphasis in the original.]

Against this backdrop — permeated with evolutionary thinking about the origin of the genome — the idea of junk DNA flourished and spread throughout the biology community.