Insulators, junk DNA, and more hype and misconceptions

The folks at Evolution News & Views (sic) can serve a very useful purpose. They are constantly scanning the scientific literature for any hint of evidence to support their claim about junk DNA. Recall that Intelligent Design Creationists have declared that if most of our genome is junk then intelligent design is falsified since one of the main predictions of intelligent design is that most of our genome will be functional.

THEME

Genomes & Junk DNA
They must be getting worried because their most recent posts sounds quite desperate. The last one is: The Un-Junk Industry. It quotes a popular press report on a paper published recently in Procedings of the National Academy of Sciences (USA). The creationists concede that the paper itself doesn't even mention junk DNA but the article in EurekAlert does.

Let''s look first at the paper (Wang et al. (2015). They are looking at sequences called "insulators" in the human genome. I'm not familiar with this term. Here's how they describe it ...

Insulators are regulatory sequence elements that help to organize eukaryotic chromatin into functionally distinct domains. Insulators can encode two different functions: enhancer-blocking activity and chromatin barrier activity. Enhancer-blocking insulators prevent the interaction of enhancer and promoter elements located in distinct domains, and chromatin barrier insulators, also known as boundary elements, protect active\ chromatin domains by blocking the spread of repressive chromatin.

That doesn't sound very specific. I can imagine that it's going to be very difficult to distinguish between sequence elements that merely disrupt chromatin because they accidentally contain protein binding sites and those that really play a biologically functional role in regulating gene expression.

The authors note that some insulators have been identified in other species. One of them, in the mouse genome, is associated with a defective SINE B2 element. Recall that SINEs (Short INterpersed Elements) are usually derived from short RNAs that have been reverse transcribed and inserted back into the genome. They are pseudogenes [Junk in Your Genome: SINES]. Many of them come from genes that were originally transcribed by RNA polymerase III.

One of the characteristics of RNA polymerase III promoters is that the transcription initiation sites are internal. Thus, when a transcript is reverse transcribed into DNA the promoter region is copied along with the rest of the molecule. When these sequences are integrated into the genome as pseudogenes, they can easily be transcribed again producing more transcripts that can serve as additional sources of cDNA. (RNA polymerase II, on the other hand, binds to sequences upstream of the transcription start site so that when pol II transcripts are copied into cDNA and re-inserted as pseudogenes they cannot be transcribed because they lack a promoter. Protein-coding genes are transcribed by RNA polymerase II.)

A typical SINE looks like the figure on the right. The short sequences labelled "A" and "B" are sequences where the RNA polymerase III holoenzyme binds to initiate transcription at the the upstream transcription start site "P."

The most common SINE in the human genome is derived from 7SL RNA giving rise to the Alu repeats [Signal Recognition Particle and Transcription of the 7SL Gene ]. There are a million copies of this particular SINE in the human genome [Junk in Your Genome: SINES]. Since they are not under selective pressure, most of them have acquired mutations, deletions, and insertions so they no longer make an RNA that resembles 7SL RNA. They are defective copies, of junk. Many of them have mutations in the RNA polymerase III binding motifs so they are not transcribed but lots of them still serve as spurious transcription start sites. The junk RNA that's produce is harmless.

The mouse B2 element is a SINE derived from a tRNA molecule. They are very common in the mouse genome. Apparently, one of them has insulator activity that's presumed to be biologically functional.

There are tRNA-derived SINES in the human genome so the authors decided to look at one particular class, called MIRs to see if they had insulator activity. Some of them are expected to have some of the characteristics of insulators because they contain the B-box sequence that serves as a binding site for RNA polymerase III. This will disrupt chromatin structure in the surrounding region as shown in Figure 1 of their paper (left).

The study identified 1,178 SINEs that could possibly be involved in an insulator-like function. Nobody knows how many of these are just defective SINES that happen to retain RNA polymerase III binding motifs but are still junk DNA. Nobody knows how many of them have been co-opted to serve a biological function in regulating expression of nearby genes. However, it's important to keep in mind that we're dealing with sequences of less than 100 bp and even if every single one of them has been co-opted to serve a biological function—an absurd possibility—it would still only amount to less that 0.01% of the genome.

Now let's look at the report published in EurekAlert [Punctuating messages encoded in human genome with transposable elements]. EurekAlert is published by the American Association for the Advancement of Science (AAAS)—the same organization that publishes Science. The Press Release copied in EurekAlert comes from Aelan Cell Technologies Inc. in San Francisco [see Punctuating messages encoded in human genome with transposable elements]. The 7th and 10th authors on the paper are affiliated with Aelan Cell Technologies Inc. The press release is published on the Georgia Institute of Technology (Atlanta, Georgia, USA) website. The senior author is located at the Georgia Institute of Technology.¹

Here's that part that excited the IDiots ...

San Francisco, CA - Since the classical studies of Jacob and Monod in the early 1960s, it has been evident that genome sequences contain not only blueprints for genes and the proteins that they encode, but also the instructions for a coordinated regulatory program that governs when, where and to what extent these genes and proteins are expressed. The execution of this regulatory code is what allows for the creation of very different cell- and tissue-types from the same set of genetic instructions found in the nucleus of every cell. A recent study published in PNAS (July 27, 2015) shows that critical aspects of this regulatory program are encoded by genomic sequence elements that were previously thought to be mere "junk DNA" with no important functions.

The vast majority of the human genome (~98% of the total genetic information) is not dedicated to encoding proteins, and this non-coding sequence was initially designated as "junk DNA" to underscore its lack of apparent function. Much of the so-called junk DNA in our genomes has accumulated over evolutionary time due to the activity of retrotransposable elements (RTEs), which are capable of moving (transposing) from one location to another in the genome and make copies of themselves when they do so. These elements have been considered as genomic parasites that exist by virtue of their ability to replicate themselves to high numbers within genomes without providing any beneficial function for the hosts in which they reside. However, recent studies on RTEs have shown that they can in fact encode important functions, and much of their functional activity turns out to be related to how genomes are regulated. RTEs have been linked to stem cell function, tissue differentiation, cancer progression and ultimately to aging and age-related pathologies.

The most interesting part of this press release—aside from the fact that it misrepresents the paper—is that it's internally contradictory. It begins by explaining that we've known about noncoding regulatory sequences since the time of Jacob and Monod (roughly 1965). The next paragraph repeats the false notion that scientists used to think that all noncoding DNA was junk. Those must have been very strange scientists who had never heard of regulatory sequences.

There was never a time when knowledgeable scientists ever thought that all noncoding DNA was junk [Stop Using the Term "Noncoding DNA:" It Doesn't Mean What You Think It Means].

Here are my two proposed rules about press releases [Stupid Harvard press release illustrates the importance of author responsibility ].

1. The press release must include the complete citation, including a link (doi). If This means delaying the press release for a day or two after the embargo is lifted then that's a small price to pay.
2. The press release should always include a notice from at least one author affirming, in writing, that the press release is a complete and accurate report of the results and conclusions that have been published in the peer reviewed literature.

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EurekAlert wants to make sure you understand that they don't take any responsibility for anything they publish: "Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system."

Wang, J., Vicente-García, C., Seruggia, D., Moltó, E., Fernandez-Miñán, A., Neto, A., Lee, E., Gómez-Skarmetad, J.L., Montoliub, L., Lunyak, V.V. and Jordan, I. K. (2015) MIR retrotransposon sequences provide insulators to the human genome. Proc. Natl. Acad. Sci. (USA) Published online July 27, 2015 [doi: 10.1073/pnas.1507253112]