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Junk DNA or a Treasure Trove?

Majid Ali, M.D.

Until recently, much of the human DNA has been considered junk DNA because it was thought to serve no useful purpose and was found to be a nuisance in the way of identifying and classifying genes. It seemed to be an unusual display of hubris on the part of geneticists. Now we know better.

Nearly half of the human genome is at present thought to live a parasitic life, contributing nothing to the metabolic, host defense, and reproductive functions of the body.24,25 One type of such sequences is called transposons or transposable element (jumping genes, in common language). These are bits of non-coding sequences in the human DNA that appear to be the offspring of sequences that broke away from their parent DNA a long time ago but learned to duplicate themselves and re-enter the mother genome. The requirements for raw materials and energy for synthesis of transposons are similar to those of useful DNA. That creates an enigma: Since perpetuation of transposable elements makes no evolutionary sense, why is it produced at all? There are yet other mysteries about such DNA: Its amount in other species is significantly lower than in humans (about 46%). Furthermore, it is scarce in homeobox gene cluster, a region of crucial importance. It seems probable that significant functions of transposable elements will be uncovered in the future to resolve those enigmas.

Four classes of transposons have been identified: (1) fossil DNA that has the ability to replicate; (2) LTR transposon that appears to be on its way to extinction; (3) LINE (Long Interspersed Element); and (4) SINE (short interspersed element). To escape easy detection and deletion by the DNA editing systems, LINE and some other transposon sequences home in on adenine-thymine-rich and gene-poor regions of chromosomes.

LINE sequences are highly successful parasites that retain full instructions to meet its every need—from copying its DNA into intermediary RNA, copying RNA back to DNA, and re-entering its chromosomal niche. SINE sequences, like some other types of transposable elements, are not normally transcribed by the cell's machinery to generate molecular messengers through which genes produce their results. That changes when cells come under stress and SINEs are transcribed to produce messengers that block molecules that otherwise slow down protein production. There is also evidence that several genes (over twenty so far) with useful functions are derived from transposable elements.

Enter in this picture Alu element, the perfect parasite of the parasite. These sequences run about 300 bases in length, are scattered throughout the chromosomes, and, numbering over a million, are the most abundant sequences in the human genome. Alu elements commandeer the LINE machinery to reproduce. Sometimes, they insert themselves into critical genes and cause genetic diseases. More importantly, they seem to have been co-opted by the body to modulate the immune response. For instance, in mice dunked in hot water, the rodent equivalent of human Alu element is activated, presumably to provide protection against acute thermal injury. Another line of evidence supporting their protective roles concerns their preferred residence in guanine-cytosine-rich regions, in close proximity of working genes. Furthermore, Alu elements respond to members of the nuclear receptor superfamily, which recognizes several hormones, including estrogens, thyroid hormone, retinoic acid, and others. The net effect: Alu element near genes influence their behavior by pitching the genes higher or lower, contributing to functional complementarities and contrarieties of genes. Junk is in the eye of the beholder.

Related Articles

* Genetics

* Re-Thinking DNA

* Intelligent language of Genes

* Junk DNA or Treasure trove

* Genes Know Their Neighbors

* A Story of Interleukins and Tumor Necrosis Factor

 

 

 

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