"Junk DNA"

Over 98 percent of DNA has largely unknown function

By Jaan Suurkula M.D.

Summary

Presently, only the function of a few percent of the DNA is known, the rest has been believed to be useless garbage, commonly called "Junk DNA" by molecular biologists.

Increasing evidence is now indicating that this DNA is not "junk" at all. Especially, it has been found to have various regulatory roles. This means that this so-called "non-coding DNA" influences the behavior of the genes, the "coding DNA", in important ways.

However, the knowledge is still very incomplete about this DNA. And there is little knowledge about the relationship between non-coding DNA and the DNA of genes.

Without this knowledge it is completely impossible to foresee and control the effect of artificial insertion of foreign genes.

This is a very important reason why genetic engineering is unsuitable for commercial application. It is still at a stage of early experimentation with very incomplete understanding about its consequences. According to the ethical standards of sound science, the products of such experimentation should be strictly contained in labortories, especially as released DNA may spread indefinitely in an uncontrollable way.


Presently, only the function of a few percent of the DNA is known, the rest has been believed to be "junk". The most exhaustive knowledge is about the genes responsible for the bodily structures, the structural genes, which are the simplest part of the system. But the knowledge about the most important part of this system, the regulator genes, is incomplete. The genetic code language of these genes is only partially known.

More than 98 percent of all DNA, was called "Junk DNA" by molecular biologists, because they were unable to ascribe any function to it. They assumed that it was just "molecular garbage". If it were "junk", the sequence of the "syllables", i.e. the nucleotides in DNA should be completely random.

However it has been found that the sequence of the syllables is not random at all and has a striking resemblance with the structure of human language (ref. Flam, F. "Hints of a language in junk DNA", Science 266:1320, 1994, see quote below). Therefore, scientists now generally believe that this DNA must contain some kind of coded information. But the code and its function is yet completely unknown.

It has been reported that the sequences of this unknown DNA are inherited and that some repetitive patterns in it seem to be associated with increased risk for cancer. Also, the DNA has been found to mutate rapidly for example in response to cancer. It has been speculated that this DNA may contribute to the regulation of cellular processes. Haig H. Kazazian, Jr., chairman of genetics at the University of Pennysylvania has recently found reasons to suspect they may be a key force for the development of new species during evolution. He thinks this DNA may be essential for increasing the plasticity of the hereditary substance.

Published at this website in May 1997.



Recent studies

Such observations as above have spurred an extensive research into "Junk DNA" in recent years, some of which is briefly presented below.

Various important roles of "Junk DNA" have been discovered in recent years.

In June 2004 a team at Harvard Medical School (HMS) reported, that they have, in a yeast, found a "Junk DNA" gene that regulates the activity of nearby genes. While common genes work by giving rise to proteins, this gene works by just being switched on. Then it blocks the activity of an adjacent gene.

Quote: "In a region of DNA long considered a genetic wasteland, HMS researchers have discovered a new class of gene."... "The researchers have evidence that the new gene, SRG1, works by physically blocking transcription of the adjacent gene, SER3. They found that transcription of SRG1 prevents the binding of a critical piece of SER3's transcriptional machinery." Source: "Junk DNA Yields New Kind of Gene", Focus, Harvard Medical School, June 4 2004.

Some studies have found that noncoding DNA plays a vital role in the regulation of gene expression during development (Ting SJ. 1995. A binary model of repetitive DNA sequence in Caenorhabditis elegans. DNA Cell Biol. 14: 83-85.), including:

  • development of photoreceptor cells (Vandendries ER, Johnson D, Reinke R. 1996. Orthodenticle is required for photoreceptor cell development in the Drosophila eye. Dev Biol 173: 243-255.),
  • the reproductive tract (Keplinger BL, Rabetoy AL, Cavener DR. 1996. A somatic reproductive organ enhancer complex activates expression in both the developing and the mature Drosophila reproductive tract. Dev Biol 180: 311-323.), and
  • the central nervous system (Kohler J, Schafer-Preuss S, Buttgereit D. 1996. Related enhancers in the intron of the beta1 tubulin gene of Drosophila melanogaster are essential for maternal and CNS-specific expression during embryogenesis. Nucleic Acids Res 24: 2543-2550.).

Over 700 studies have demonstrated the role of non-coding DNA as enhancers for transcription of proximal genes. This includes a/o:

  • eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) (Tiffany HL, Handen JS, Rosenberg HF. 1996. Enhanced expression of the eosinophil-derived neurotoxin ribonuclease (RNS2) gene requires interaction between the promoter and intron. J Biol Chem 271: 12387-12393),
  • the variable region of the rearranged immunoglobulin mu (IgM) gene (Jenuwein T, Forrester WC, Fernandez-Herrero LA, Laible G, Dull M, Grosschedl R. 1997. Extension of chromatin accessibility by nuclear matrix attachment regions. Nature 385: 269-272.; Nikolajczyk BS, Nelsen B, Sen R. 1996. Precise alignment of sites required for mu enhancer activation in B cells. Mol Cell Biol 16: 4544-4554),
  • the alpha-globin gene (Bouhassira EE, Kielman MF, Gilman J, Fabry MF, Suzuka S, Leone O, Gikas E, Bernini LF, Nagel RL. 1997. Properties of the mouse alpha-globin HS-26: relationship to HS-40, the major enhancer of human alpha-globin gene expression. Am J Hematol 54: 30-39),
  • the activin beta A subunit gene (Tanimoto K, Yoshida E, Mita S, Nibu Y, Murakami K, Fukamizu A. 1996. Human activin betaA gene. Identification of novel 5' exon, functional promoter, and enhancers. J Biol Chem 271: 32760-32769).

Over 60 studies have demonstrated the role of non-coding DNA as silencers for suppression of transcription of proximal genes. Such silencer genes include a/o:

  • apolipoprotein A-II gene (Bossu JP, Chartier FL, Fruchart JC, Auwerx J, Staels B, Laine B. 1996. Two regulatory elements of similar structure and placed in tandem account for the repressive activity of the first intron of the human apolipoprotein A-II gene. Biochem J 318: 547-553.),
  • the osteocalcin gene (Goto K, Heymont JL, Klein-Nulend J, Kronenberg HM, Demay MB. 1996. Identification of an osteoblastic silencer element in the first intron of the rat osteocalcin gene. Biochemistry 35: 11005-11011),
  • the 2-crystallin gene (Dirks RP, Kraft HJ, Van Genesen ST, Klok EJ, Pfundt R, Schoenmakers JG, Lubsen NH. 1996. The cooperation between two silencers creates an enhancer element that controls both the lens-preferred and the differentiation stage-specific expression of the rat beta B2-crystallin gene. Eur J Biochem 239: 23-32).

Some studies indicate that non-coding DNA regulate translation of proteins. This includes a/o

  • the Lipoprotein Lipase gene (Ranganathan G, Vu D, Kern PA. 1997. Translational Regulation of Lipoprotein Lipase by Epinephrine Involves a Trans-acting Binding Protein Interacting with the 3' Untranslated Region. J Biol Chem 272: 2515-2519)
  • glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase genes (Bermano G, Arthur JR, Hesketh JE. 1996. Role of the 3' untranslated region in the regulation of cytosolic glutathione peroxidase and phospholipid-hydroperoxide glutathione peroxidase gene expression by selenium supply. Biochem J 320: 891-895),
  • the luteinizing hormone/human chorionic gonadotropin receptor gene (58. Lu DL, Menon KM. 1996. 3' untranslated region-mediated regulation of luteinizing hormone/human chorionic gonadotropin receptor expression. Biochemistry 35: 12347-12353),
  • the thyrotropin receptor gene (Kakinuma A, Chazenbalk G, Filetti S, McLachlan SM, Rapoport B. 1996. BOTH the 5' and 3' noncoding regions of the thyrotropin receptor messenger ribonucleic acid influence the level of receptor protein expression in transfected mammalian cells. Endocrinology 137: 2664-2669),
  • the interleukin 1 type I receptor gene (Ye K, Vannier E, Clark BD, Sims JE, Dinarello CA. 1996. Three distinct promoters direct transcription of different 5' untranslated regions of the human interleukin 1 type I receptor: a possible mechanism for control of translation. Cytokine 8: 421-429)

Russian research adds a quantum physics perspective

Recently, experimental results by Gariaev et al indicate that some, and perhaps important, aspects of genetic regulation are mediated at a quantum level. Moreover, in this respect they suggest that non-coding "Junk DNA" plays a crucial role, see

  • "The DNA-wave Biocomputer" (an MS Word document) and
  • "Crisis in Life Sciences. The Wave Genetics Response". Excerpt:

    "It appears that the languages we were looking for, are, in fact, hidden in the 98%, "junk" DNA contained in our own genetic apparatus [4]. The basic principle of these languages is similar to the language of holographic images [5] based on principles of laser radiations of the genetic structures [6] which operate together as a quasi-intelligent system, as in [3] It particularly important to realize that our genetic devices actually perform real processes which supplement the triplet model of the genetic code."


Conclusion

The idea that a major part of our DNA is "garbage" ignored the fact that a key feature of biological organisms is optimal energy expenditure. To carry enormous amounts of unnecessary molecules is contrary to this fundamental energy saving feature of biological organisms. Increasing evidence are now indicating many important functions of this DNA, including various regulatory roles.

This means that this so-called non-coding DNA influences the behavior of the genes, the "coding DNA", in important ways. Still there is very little knowledge about the relationship between non-coding DNA and the DNA of genes.

This adds to other factors making it impossible to foresee and control the effect of artificial insertion of foreign genes.


Appendix

JUNK DNA- May Not Be Junk After All

(Quoted from Gene exchange no 2, 1996)

In another reminder that we may not understand the full ramifications of genetic engineering, Science magazine recently reported new work on the function of genetic material*. Scientists have long been puzzled by the fact that fully 97% of the DNA in human cells does not code for proteins and appears to consist of meaningless sequences. The possibility that this apparently useless DNA has some as yet unknown function continues to tantalize scientists.

The Science article reports on a paper suggesting that the non-coding 97% of the DNA, commonly referred to as junk DNA, might have a function. The authors of the paper employed linguistic tests to analyze junk DNA and discovered striking similarities to ordinary language. The scientists interpret those similarities as suggestions that there might be messages in the junk sequences, although its anyone s guess as to how the language might work. * F. Flam, Hints of a language in junk DNA, Science 266:1320, 1994.


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