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Monday, May 10, 2021

MIT Professor Rick Young doesn't understand junk DNA

Richard ("Rick") Young is a Professor of Biology at the Massachusetts Institute of Technology and a member of the Whitehead Institute. His area of expertise is the regulation of gene expression in eukaryotes.

He was interviewed by Jorge Conde and Hanne Winarsky on a recent podcast (Feb. 1, 2021) where the main topic was "From Junk DNA to an RNA Revolution." They get just about everything wrong when they talk about junk DNA including the Central Dogma, historical estimates of the number of genes, confusing noncoding DNA with junk, alternative splicing, the number of functional RNAs, the amount of regulatory DNA, and assuming that scientists in the 1970s were idiots.

In this episode, a16z General Partner Jorge Conde and Bio Eats World host Hanne Winarsky talk to Professor Rick Young, Professor of Biology and head of the Young Lab at MIT—all about “junk” DNA, or non-coding DNA.

Which, it turns out—spoiler alert—isn’t junk at all. Much of this so-called junk DNA actually encodes RNA—which we now know has all sorts of incredibly important roles in the cell, many of which were previously thought of as only the domain of proteins. This conversation is all about what we know about what that non-coding genome actually does: how RNA works to regulate all kinds of different gene expression, cell types, and functions; how this has dramatically changed our understanding of how disease arises; and most importantly, what this means we can now do—programming cells, tuning functions up or down, or on or off. What we once thought of as “junk” is now giving us a powerful new tool in intervening in and treating disease—bringing in a whole new category of therapies.

Here's what I don't understand. How could a prominent scientist at one of the best universities in the world be so ignorant of a topic he chooses to discuss on a podcast? Perhaps you could excuse a busy scientist who doesn't have the time to research the topic but what excuse can you offer to explain why the entire culture at MIT and the Whitehead must also be ignorant? Does nobody there ever question their own ideas? Do they only read the papers that support their views and ignore all those that challenge those views?

This is a very serious question. It's the most difficult question I discuss in my book. Why has the false narrative about junk DNA, and many other things, dominated the scientific literature and become accepted dogma among leading scientists? Soemething is seriously wrong with science.


14 comments :

  1. So what's the explanation? A lot of people just don't like the idea that most of your genome is junk. Why? It used to be because they thought selection was more powerful than that. I remember in my undergrad evolution course learning about the big fight between neutralists and selectionists over allozyme variation, which the neutralists seem to have won. And it seems that the selectionists were sustained by faith alone, not works. Anyway, it's not just humans that aren't allowed to have junk.

    And then we get the dog's ass plot showing that humans are the pinnacle of genetic complexity; there, the motivation seems clear: science must support human exceptionalism, and the data must be carefully chosen to reflect that.

    Selectionism and exceptionalism would both seem to contribute. What else?

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    1. I suspect these issues are exacerbated by the universities and institutions advertising their work with click-bait titles.

      We are constantly bombarded with grandiose science press releases declaring the deaths of stifling old paradigms, and junk-DNA appears to have become this popular dragon every new scientist can help slay.

      So in an extremely competitive field, everyone wants solve the "riddle" and "mystery" of the "dark matter in the genome" and to cause the next big "paradigm shift", and these same people then go on to contribute the same misleading press releases and exaggerated claims in collaboration with journalists and websites trying to bait clicks. And on and on the cycle goes.

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    2. Setting up a false paradigm and then shifting it is called a paradigm SHAFT (thanks to Diogenes for naming this tactic). That's part of the problem but another important part of the counter-narrative is lying about the true history of the field.

      The anti-junk proponents are a lot like the Republican base in the USA; they've heard the same lies so many time that they've come to believe them. They no longer question these false beliefs.

      Here's an example of all that from Alan McHughen's 2020 book "DNA Demystified." As you read it, keep in mind that I corresponded with McHughen and he allowed me to post his position on my blog.

      https://sandwalk.blogspot.com/2020/08/alan-mchughen-defends-his-views-on-junk.html

      He then terminated the discussion by sayig that he was too busy to continue.

      Here's what he wrote in his book.

      When it was first discovered, the nongenic DNA was sometimes called—somewhat derisively by people who didn't know better—"junk DNA" because it had no obvious utility, and they foolishly assumed that if it wasn't carrying coding information it must be useless trash.

      In evolutionary terms, a DNA sequence with no function is simply dead weight that gets carried along, at some cost to the organism, to be jettisoned at the first opportunity. If the sequences were not adaptively important, evolution would have kicked them out as expendable excess baggage. The fact that nonrecipe DNA continues to be part of the human and other eukaryotic genomes over millions of years indicates that there is some adaptive value to carrying the "junk baggage" along, even if that value remains unclear to us today.

      In addition to various putative regulatory and structural functions, recent evidence indicates that mutations in the integernic noncoding DNA leads to a increase in susceptibility to various diseases. If confirmed, it would show a clear adaptive value to "junk" DNA.

      Today, we appreciate that this is not useless junk and now call it noncoding DNA.

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  2. Could over specialization be the problem? How much does the usefulness of Junk DNA matter to their research programs? If all you know is 1) It doesn't code for proteins, 2) some of it codes for useful stuff in various ways and 3) some people call it "junk" then is it easy to invent an off the cuff narrative along the lines of "people used to think this, but now we think that" regardless of the actual history.

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  3. "The central dogma" is one of the most unfortunate misnomers in biology.

    Speaking of dogma, here's a new challenge to the WHO report on the origin of Covid-19:

    https://science.sciencemag.org/

    Should we assume that all of the authors are white, anti-asian QAnon cultists as was implied here in a previous post?

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  4. Going back on topic, I think the Harvard and MIT credentials are overrated and/or devalued.

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  5. I think that, in addition to the arguments already mentioned, also incompetence could exacerbate the problem of renouncement of junk DNA. The following paper was appearingly written only by psychologists and psychatrists (according to the institutional adresses), but the title "Evolution of genetic networks for human creativity" (Open Access: https://www.nature.com/articles/s41380-021-01097-y) suggests genetical and evolutionary expertise.
    The abstract asserted that modern humans have 267 species-specific genes which supposedly are involved in the emergence of human creativity. 95% of these "genes" (simple transscripts) are not protein-coding. After reading the paper, the evidence for this original message was somewhat difficult the evaluate, but very weak and clearly incompatible with functions and evolutionary biology of the very sparsely distributed new genes of other organisms.

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    1. Incompetence is another word for stupidity and it's definitely a problem. In this case the authors don't understand what a gene is so they assume that any stretch of DNA that's complementary to a transcript has to be a gene.

      What they're actually looking at is a lot of junk RNA transcripts.

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    2. I concur. Garbage in, garbage out is what has happened here. There are a number of erroneous assumptions. A quick glance at the supplementary material suggests that none of the 5% coding genes that are supposed to distinguish humans from Neanderthals are unique to humans either.

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  6. Have you seen this paper : doi: 10.3390/life11040342 ?
    Claims there is "no room for junk".

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    1. It has zero actaul discussion of the case for junk DNA. Some papers arguing for junk are cited, but the arguments contained therein are not responded to or rebutted. No actual explanation is provided anywhere for the variations in c-value between species, the constituents of most junk-DNA (selfish genetic elements) and their relationships to things like population size, mutation rates, neutral theory, and so on.

      It's total trash.

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  7. The FAQ of the Human Genome Project says "Each of the estimated 30,000 genes in the human genome makes an average of three proteins."

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    1. Yes, isn't that shocking? The National Institutes of Health (NIH) have no evidence to support their claim that we have 30,000 protein-coding genes. (The actual number is less than 20,000.)

      They have no evidence to support their claim that each gene produces an average of three different functional proteins.

      So, why are they publishing incorrect information?

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  8. Oboyoboyoboy you're going to love this one, Larry. It does actually make reference to some defenses of junk DNA, before dismissing them.
    It popped up in my news feed. It is here:
    https://www.quantamagazine.org/the-complex-truth-about-junk-dna-20210901/
    Note that it is "the truth".

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