This article series has been exploring the issue of so-called “junk” DNA being used as evidence for evolution. Many biologists argue that these DNA segments must be the product of naturalistic processes because (1) they appear to be functionless (therefore labeled “junk”); and (2) they are frequently located in the same place in the genomes of related organisms. But scientific research puts this perspective into question.
In part 1 I highlight the history of the junk DNA argument and highlighted key concepts of cell biology. In part 2 of this series, I discussed the many structural motifs present in Alu elements, a type of junk DNA used to support evolutionary theory. As I noted in part 2, there is a saying in biochemistry that “structure is function.” That is, the structure of a molecule determines its function. The two can’t be separated, and knowing the molecule’s structure makes its function logical. That’s why I chose to review the motifs present in Alu elements before talking about the Alu elements’ function.
In the absence of the many structural motifs present in Alu elements, they could not possess all the functions that they do. But with these motifs an Alu element looks very much like a versatile and designed segment of DNA, not just a random segment. I’ll have more to say about the design of repetitive elements towards the end of this series.
The Function of Alu Elements
Scientists were accustomed to thinking that anything useful in the genome was going to have a unique sequence—like a region of DNA that codes for a protein. The fact that the human genome contains over a million copies of Alu elements influenced evolutionists to deem these elements as likely useless. As it turns out, their repetitiveness is a requirement for Alu elements’ architectural functions.
Allow me to explain. In order to fit into the cell, DNA must be compacted into a structure called chromatin (see part 1). The first level of DNA compaction is the formation of nucleosomes. (Here’s where Alu elements come into play.) Alu elements can accommodate up to two nucleosomes in each element (see part 2). Scientists now know that other nucleosomes are distributed in an even fashion radiating out from the nucleosomes in Alu elements.1 Thus, the placement of nucleosomes in Alu elements directs the placement of nucleosomes in other areas of the genome. This placement is necessary for compaction and plays a role in determining whether or not DNA is available for transcription.
Other Types of Repetitive Elements
Alu elements are not the only repetitive, noncoding DNA segments with architectural functions in the cell. Other conserved noncoding regions in DNA have been shown to contain special sequences known as matrix attachment regions (MARs).2 These DNA sequences anchor chromosomes to the nuclear matrix—the network of fibers in the nucleus of the cell that form its internal “skeleton.” This dynamic “skeleton” is thought to play a significant role in gene regulation.
The cell is quite a complex and crowded place. If we were able to glimpse the cell in action at a very high magnification, it would appear, to us, as chaotic. Yet the cell’s internal organization is, in fact, highly ordered. The cell possesses its own internal infrastructure, and the “architecture” provided by repetitive DNA elements is part of that infrastructure.
Other functions of repetitive DNA require that these elements be scattered throughout the genome. Scientists have demonstrated that RNAs transcribed from DNA’s noncoding regions are both necessary and sufficient to establish an area of high transcriptional activity in the regions adjacent to the one from which the RNA originated.3 The DNA’s noncoding region is acting as a “regional” controller of the gene expression in its area. RNAs from other long noncoding DNA sequences have been shown to coordinate long-range gene activity during an organism’s development.4 These “architectural,” regional, and long-range control functions require that repetitive DNA, including Alu elements, be dispersed throughout the genome.
The repetitive nature of Alu elements contributes to the role they play in binding transcription factors to regulate transcription. (I’ll discuss this role in detail later in this article series). As mentioned in part 2, Alu elements contain binding sites for as many as 66 different transcription factors.5 Since there are so many (over a million) Alu elements, there are many binding sites for the same transcription factor. Scientists now realize that the presence of multiple binding sites allows for more complex and subtle patterns of transcription regulation.6 In fact, the orientation of repeated binding sites relative to one another and the spacing between the binding sites can determine whether the transcription factor increases or decreases transcription.7 The repetitiveness of these transcription factor binding sites is not meaningless; rather, it is essential to Alu elements’ function and to the development of complex regulatory networks in biologically sophisticated organisms.
One transcription factor that binds to Alu elements deserves special attention—the p53 tumor suppressor, the central transcription factor in a complex regulatory network. Thought to regulate over 1,000 genes,8 p53 determines whether a cell grows and divides, becomes specialized, or dies. It determines the fate of the cell based on multiple signals that it responds to. In fact, p53 is so important that scientists dubbed it the “guardian of the genome.” Recently, a research team determined that there may be 400,000 binding sites for p53 in human Alu elements.9 Even more significant, these sites seem to also be response elements—that is, a segment of DNA where p53 binds and, because of that binding, affects transcription at a nearby gene.
There are slightly over a million copies of Alu elements in the human genome, and if 200,000 to 400,000 of them serve as binding sites for p53 and others serve architectural, regional, and long-range control functions and as binding sites for 65 other transcription factors, it quickly becomes evident that all those Alu elements are quite busy in the cell. And, one of the very aspects of Alu elements that originally caused evolutionists to view them as useless—repetitiveness—has turned out to be essential to their function.
The information in this article alone can make your head spin, yet we’ve barely begun to cover the functions of Alu elements. Next week, we’ll explore other functions of this so-called junk DNA.
1. Yoshiaki Tanaka et al., “Effects of Alu Elements on Global Nucleosome Positioning in the Human Genome,” BMC Genomics 11 (May 17, 2010): 309–19.
2. Galina V Glazko et al., “A Significant Fraction of Conserved Noncoding DNA in Human and Mouse Consists of Predicted Matrix Attachment Regions,” Trends in Genetics 19 (March 2003): 119–24.
3. Victoria V. Lunyak et al., “Developmentally Regulated Activation of a SINE B2 Repeat as a Domain Boundary in Organogenesis,” Science 317 (July 13, 2007): 248–51.
4. Kevin C. Wang, “A Long Noncoding RNA Maintains Active Chromatin to Coordinate Homeotic Gene Expression,” Nature (April 7, 2011), 120–4, doi:10.1038/nature09819.
5. Paz Polak and Eytan Domany, “Alu Elements Contain Many Binding Sites for Transcription Factors and May Play a Role in Regulation of Developmental Processes,” BMC Genomics 7 (June 1, 2006): 133–47.
6. James A. Shapiro and Richard von Sternberg, “Why Repetitive DNA Is Essential to Genome
Function,” Biological Reviews of the Cambridge Philosophical Society 80 (2005): 227–50.
7. Chiou-Hwa Yuh, H. Bolouri, and E. H. Davidson,“Genomic cis-regulatory Logic: Experimental and Computational Analysis of a Sea Urchin Gene,”Science 279 (March 20, 1998): 1896–902; Itai Beno et al., “Sequence-Dependent Cooperative Binding of p53 to DNA Targets and its Relationship to the Structural Properties of the DNA Targets,” Nucleic Acids Research 39 (March 1, 2011): 1919–32.
8. Feng Cui, M. V. Sirotin, and V. B. Zhurkin, “Impact of Alu Repeats on the Evolution of Human p53 Binding Sites,” Biology Direct 6 (2011): 2–20.