Alan McHughen is the author of a recently published book titled DNA Demystified. I took issue with his stance on junk DNA [More misconceptions about junk DNA - what are we doing wrong?] and he has kindly replied to my email message. Here's what he said ...
I don't want to discuss the first point because it's a red herring. As far as I can tell, the only people who dislike the word "junk" are doing so because they don't believe it's an accurate description of a substantial part of our genome. So let's just discuss the second point.
If I understand him correctly, his second point is that the term "junk" DNA was originally synonymous with "noncoding" DNA and, as he explains in his book, the scientists who used the word "junk" did so because they thought that all noncoding DNA was useless. His position now is that some noncoding DNA has been shown to be functional thereby refuting the original definition.
Let me remind readers of what he wrote in his book.
Alan McHughen and I are from the same era but we clearly hung out with different crowds. My mentors were members of the 'phage group who were actively working on genes and their regulation and actively investigating other functional elements. I attended summer meetings at Cold Spring Harbor for five years (1969-73) and I can assure you that anyone who stood up in front of that group and said that all noncoding DNA was junk would have been laughed out of the room.
Here's what I knew in the early 1970s.
Let's look at the 1972 paper by Susumu Ohno because that's the paper that made the term "junk DNA" popular. Ohno was an evolutionary biologist and a molecular geneticist and he was familiar with the thinking of the scientists in the 'phage group. He begins his paper by referring to the C-value paradox because that's an important part of the early thinking about junk DNA. Why do some species have a lot more DNA than others? ... it's because the excess DNA is junk. That's still the only reasonable explanation of the so-called C-value Paradox.
Ohno then discusses the genetic load argument by pointing out that we can only have about 30,000 genes or our species would go extinct. He estimates that only about 6% of our genome could be functional and references Kimura and Ohta's seminal paper on mutation rates and effective population sizes (Kimura and Ohta, 1971). He then says ....
So, I do not agree with Alan McHughen that the original definition of junk DNA equated it with noncoding DNA and I do not agree with him that the discovery of regulatory sequences "justify trashing the 'junk' label." I still think the genetic load argument has to be dealt with by opponents of junk DNA.
I'm still not exactly sure where the revisionist history comes from. Perhaps someone can help me out by coming up with a reference from the 1970s where some knowledgeable scientist makes the point that all noncoding DNA must be junk.
Now let's move on to 2020. There are a large number of experts who think that most of our genome is junk. I'd like to ask Alan how he deals with the evidence for junk DNA and what evidence he can offer to support the claim that most of our genome is functional.
Here's a paper from my friends Alex Palazzo and Ryan Gregory (Palazzo and Gregory, 2017) and another one from Ford Doolittle and Tyler Brunet (Doolittle and Brunet, 2017). They are good starting points for further discussion.
I wrote DNA Demystified with the knowledge and intent for spurring debate and discussion on a number of issues.Alan McHughen appears to dislike the term "junk" DNA because of its negative image and also because he thinks that the original definition has been disproved.
My position on 'junk DNA' hasn't changed much since I first learned about it in the early to mid- 1970s. My primary concern now is that the term 'junk' is inappropriate, as it conveys an immediate negative image and engenders an emotional response. There may well be DNA sequences that serve no useful purpose and are only wastage, carried along through the generations as burdensome baggage (i.e. the 'ordinary' definition of 'junk'). Initially. as I'm sure you remember, all non-coding DNA was considered (by some) as "Junk DNA". I was never among them, expecting that eventually scientists would find some adaptive value to at least some of the non-coding sequences. I am happy to accept the data that this has come to pass-- that the now well-documented regulatory functions alone, for example, justify trashing the 'junk' label.
If there are tracts of truly useless DNA, it would be interesting to see how the organism responds when such sequences are deleted from the genome. That would be a true test of whether or not the excised DNA sequences were 'junk'.
You are free to disagree, of course, but I wanted to clarify my position.
I don't want to discuss the first point because it's a red herring. As far as I can tell, the only people who dislike the word "junk" are doing so because they don't believe it's an accurate description of a substantial part of our genome. So let's just discuss the second point.
If I understand him correctly, his second point is that the term "junk" DNA was originally synonymous with "noncoding" DNA and, as he explains in his book, the scientists who used the word "junk" did so because they thought that all noncoding DNA was useless. His position now is that some noncoding DNA has been shown to be functional thereby refuting the original definition.
Let me remind readers of 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.My position is that there was never a time when knowledgeable scientists ever said that all noncoding DNA was junk. They never assumed that the only functional sequences in our genome were protein-coding sequences. Junk DNA was always defined as excess DNA that had no function and that definition is still valid.
Alan McHughen and I are from the same era but we clearly hung out with different crowds. My mentors were members of the 'phage group who were actively working on genes and their regulation and actively investigating other functional elements. I attended summer meetings at Cold Spring Harbor for five years (1969-73) and I can assure you that anyone who stood up in front of that group and said that all noncoding DNA was junk would have been laughed out of the room.
Here's what I knew in the early 1970s.
- Some genes did not encode proteins. Ribosomal RNA genes and tRNA genes were discussed in the first edition of Watson's textboook in 1965. We all knew about these functional noncoding sequences.
- Regulatory sequences such as promoters and operators controlled the expression of genes. The noncoding regulatory sequences of the lac operon and of the major operons of bacteriophage lambda were well known. Nobody ever thought that these noncoding regions were junk.
- We knew about centromeres—noncoding functional DNA.
- We knew about origins of replication—noncoding functional DNA. (I was working on DNA replication.)
Let's look at the 1972 paper by Susumu Ohno because that's the paper that made the term "junk DNA" popular. Ohno was an evolutionary biologist and a molecular geneticist and he was familiar with the thinking of the scientists in the 'phage group. He begins his paper by referring to the C-value paradox because that's an important part of the early thinking about junk DNA. Why do some species have a lot more DNA than others? ... it's because the excess DNA is junk. That's still the only reasonable explanation of the so-called C-value Paradox.
Ohno then discusses the genetic load argument by pointing out that we can only have about 30,000 genes or our species would go extinct. He estimates that only about 6% of our genome could be functional and references Kimura and Ohta's seminal paper on mutation rates and effective population sizes (Kimura and Ohta, 1971). He then says ....
Aside from conventional structural genes and regulatory genes, this 6% should include the promoter and operator region which are situated adjacent to each structural gene, for these regions can definitely sustain deleterious mutations. [His emphasis.]Ohno did NOT think that all noncoding DNA was junk and neither did anyone else who knew what they were talking about. Ohno, and many others, knew perfectly well that regulatory sequences exist and that they are not junk. These experts did not foolishly assume "that if it wasn't carrying coding information then it must be useless trash."
So, I do not agree with Alan McHughen that the original definition of junk DNA equated it with noncoding DNA and I do not agree with him that the discovery of regulatory sequences "justify trashing the 'junk' label." I still think the genetic load argument has to be dealt with by opponents of junk DNA.
I'm still not exactly sure where the revisionist history comes from. Perhaps someone can help me out by coming up with a reference from the 1970s where some knowledgeable scientist makes the point that all noncoding DNA must be junk.
Now let's move on to 2020. There are a large number of experts who think that most of our genome is junk. I'd like to ask Alan how he deals with the evidence for junk DNA and what evidence he can offer to support the claim that most of our genome is functional.
Here's a paper from my friends Alex Palazzo and Ryan Gregory (Palazzo and Gregory, 2017) and another one from Ford Doolittle and Tyler Brunet (Doolittle and Brunet, 2017). They are good starting points for further discussion.
Palazzo, A.F. and Gregory, T.R. (2014) The Case for Junk DNA PLOS Genetics 10:e1004351. [doi: 10.1371/journal.pgen.1004351]
With the advent of deep sequencing technologies and the ability to analyze whole genome sequences and transcriptomes, there has been a growing interest in exploring putative functions of the very large fraction of the genome that is commonly referred to as “junk DNA.” Whereas this is an issue of considerable importance in genome biology, there is an unfortunate tendency for researchers and science writers to proclaim the demise of junk DNA on a regular basis without properly addressing some of the fundamental issues that first led to the rise of the concept. In this review, we provide an overview of the major arguments that have been presented in support of the notion that a large portion of most eukaryotic genomes lacks an organism-level function. Some of these are based on observations or basic genetic principles that are decades old, whereas others stem from new knowledge regarding molecular processes such as transcription and gene regulation.
Doolittle, W.F. and Brunet, T.D. (2017) On causal roles and selected effects: our genome is mostly junk BMC biology 15:116. [doi: 10.1186/s12915-017-0460-9]
The idea that much of our genome is irrelevant to fitness—is not the product of positive natural selection at the organismal level—remains viable. Claims to the contrary, and specifically that the notion of “junk DNA” should be abandoned, are based on conflating meanings of the word “function”. Recent estimates suggest that perhaps 90% of our DNA, though biochemically active, does not contribute to fitness in any sequence-dependent way, and possibly in no way at all. Comparisons to vertebrates with much larger and smaller genomes (the lungfish and the pufferfish) strongly align with such a conclusion, as they have done for the last half-century.
Kimura, M. and Ohta, T. (1971) Protein polymorphism as a phase of molecular evolution Nature 229:467-469. [doi: 10.1038/229467a0]
