Some evidence ALUs and SINES aren’t junk and garbologists are wrong

Larry Moran, Dan Graur and other garbologists (promoters of the junkDNA perspective), have argued SINES and ALU elements are non-functional junk. That claim may have been a quasi-defensible position a decade ago, but real science marches forward. Dan Graur can only whine and complain about the hundreds of millions of dollars spent at the NIH and elsewhere that now strengthens his unwitting claim in 2013, “If ENCODE is right, Evolution is wrong.”

Larry said in Junk in Your Genome: SINES

In humans, the largest family of SINEs is called Alu elements after the fact that the sequence is cleaved by the restriction endonuclease Alu. These SINEs are also derived from 7SL RNA but the rearrangement is different from that in mouse. (They have a common ancestor.) There are about one million Alu elements in the human genome.

SINEs make up about 13% of the human genome. The largest proportion, by far, is Alu elements but there are small numbers of SINEs derived from other cellular RNAs such as the U RNAs required for splicing and snoRNAs (Garcia-Perez et al. 2007).

SINEs are parasites (selfish DNA). They are not essential for human survival and reproduction, especially the huge majority of SINEs that are defective. Thus, at least 13% of the human genome is clearly junk. The total amount of junk DNA contributed by all transposable elements is 44% of the genome (Kidwell 2005).

Thursday, February 07, 2008

Where to begin? First off, Larry’s claim was made over 8 years ago. Larry ran the risk of becoming the butt of jokes since a scientific discovery here and there could overturn his precarious claims.

Below is a video associated with a 2015 paper from National Academy of Sciences, a mere 7 years after Larry’s claim was made. One important aspect of SINES are the CTFC binding site motifs often found in SINEs. The motifs can’t be randomly located, otherwise they would not properly create functional chromatin extrusion loops. Further, these CTFC binding site motifs must be coordinated to “point” in the right direction many base pairs away in order for these extrusion loops to form. See this amazing video of extrusion loops and CTFC binding sites (which are often found in SINES):



We therefore searched for an alternative mechanism for the de novo creation in a common mammalian ancestor of the thousands of CTCF-binding events now found throughout mammals. Despite the generally high conservation of CTCF motif-word usage, we noted that specific sets of motif-words were overrepresented in rodents (mouse and rat), dog, and opossum (Figure 4A). We found that the vast majority of these overrepresented motif-words are embedded within SINE transposons (Figures 4B and ​andS4S4).

The following 2015 paper lists many roles of ALU elements, about 7 years after Larry’s claims about ALUs were vomited onto the internet. Will he feel as confident now about his claims or will retractions be forthcoming?

The role of Alu elements in the cis-regulation of RNA processing

Alu elements are an important engine for functional diversity within the primate transcriptome. As building blocks of extra genetic material, retroelements are used to invent new ways to vary mRNA. The almost 300 nt long Alu element is an ideal player for several reasons: (1) Alus are frequently inserted into non-coding regions of pre-mRNAs, (2) when transcribed, they easily form stable secondary structures that seed a number of different RNA processing events, and (3) small changes to their sequence make them targets for a number of RNA-binding proteins that regulate gene expression. Depending on its location and specific sequence, the Alu element can induce different RNA processing events (Fig. 5). If two inverted Alus reside on each side of an exon, they can form a double-stranded RNA structure that may induce back-splicing and the formation of circular RNA. An intronic Alu with a mutated or edited sequence can induce alternative splicing or Alu exonization. Inverted repeat elements can also contribute to transcript variations in a more fine-tuned manner by inducing A-to-I editing within coding sequence. Also, Alus in introns and 3′UTRs can provide both miRNAs and their target sequences. In this review, we have only highlighted a few examples of how Alu elements may contribute to transcriptome variation in primates. These effects certainly combine with the better explored genomic variations that Alus create. Future studies will most likely reveal additional mechanisms on how these elements modulate our genetics.

Here is an example from that paper:
alu example figure 5

Possible Alu-induced RNA processing events. a Inverted Alus on each side of an exon that form a dsRNA structure may induce exonic RNA circularization. b An intronic Alu with a mutated or edited sequence can induce alternative splicing and/or Alu exonization. c Inverted Alu elements forming a dsRNA structure frequently induce A-to-I editing at nearby sites. d Within introns Alus can contribute to maturation of miRNAs. eAlu elements in 3′UTRs may act as miRNA targets

154 thoughts on “Some evidence ALUs and SINES aren’t junk and garbologists are wrong

  1. stcordova: Money talks, it’s #1 in Amazon in biochemistry.

    We accept your total concession that you are unable to back up your claim about how the book is regarded.

    And this has got to hurt:Darwin’s Black Box ranks higher in biochemistry than Larry Moran’s textbook.

    That’s idiotic. Darwin’s black box is a pop-sci book, not a fucking biochemistry textbook, while Moran’s is a university textbook in a specialized field. You can’t compare the two you silly person.

    By that childish standard, you better make Richard Dawkins your lord and savior given that his God Delusion book has sold over three million copies.

  2. stcordova: You mean some of the strongest evidence in all of science: comparative genetics.

    No, I mean evolutionary biology as in:

    In science’s pecking order, evolutionary biology lurks somewhere near the bottom…

    Jerry Coyne

    Which has of course zero to do with the strength of the evidence from comparative genetics, but nice try.

  3. stcordova: Evolutionary biologist hypothesis things on the sketchiest of evidence, and then when confronted with highly credible experimental evidence, they then start becoming skeptics and naysayers.

    Where is the experimental evidence that all Alu sequences are functional?

  4. stcordova: And this has got to hurt: Darwin’s Black Box ranks higher in biochemistry than Larry Moran’s textbook.

    First, that’s factually untrue. Second, I don’t accept position on Amazon’s best-seller list as an index of respectability. It would probably be against the rules to accuse you of moral bankruptcy. Wouldn’t it?

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