Junk DNA
Author: Nessa Carey

Background

The subject of this book is perhaps the most inappropriately designated concept in science. Far from connoting ‘worthless garbage‘, the book is an eloquent testament to the fundamental importance of junk DNA to cellular function. Although it is dubbed ‘junk’ because it does not code for protein, the book provides sufficient demonstration of its influential role in regulating gene expression during protein synthesis, and its diverse functions such as maintaining DNA in its compact structure, and anchoring chromosomes during cell division. The key message of the book is the strong case it makes that junk DNA, comprising ‘over 98% of the DNA in a human cell’, is as important as coding DNA in cellular function; as vulnerable to disease-causing mutations; and as relevant in driving ‘evolutionary complexity‘. The book turned out to be a most enlightening exploration of a part of the DNA which is as surprising in its intricacy as it is in its utility (pages 3-6 and 24).

Synopsis

The immense complexity of junk DNA is a central theme of the book which the author explored from its structural and functional perspectives. For example, in illustrating the building blocks of junk DNA, she pointed out that a surprising 40% of its makeup is derived from ‘parasitic elements‘ – ‘genetic interlopers‘ which are mainly of viral origin. She elaborated on how, overt time, these genetic colonisers invaded and settled in the human genome, and how they have taken over several regulatory functions. The author also described how this component of junk DNA tends to form repetitive elements, the larger of which are referred to as endogenous retroviruses or ERVs, and the smaller as ‘interspersed repetitive elements‘. Another example of the peculiar structure of junk DNA is the telomere, a non-coding DNA which is located at the end of every chromosome, and which consists of a repeating series of the same six base pairs – TTAGGG. The book highlighted the important function of telomeres in ageing and mortality – inevitable outcomes of the tendency of the telomeres to progressively shorten with every cell division. Because of this, the author metaphorically depicted telomeres as ‘molecular clocks…counting us down as we age’ (pages 5, 37-31, 41 and 49-62).

Just as impressive as the intricate structure of junk DNA are the critically important diverse functions it subserves. One of the most remarkable the book explored is its role in reproduction, an illustrative example of which is the epigenetic mechanism of imprinting – the process whereby foetal genes are marked by their parental origin. To demonstrate the influence of this ‘parent-of-origin effect‘, the author painted a fascinating picture of how the development of the placenta and embryo is driven by paternally imprinted genes, whilst the maternally imprinted genes favour the nourishment of the mother at the expense of placental development. The author explained that the rationale behind this ‘epigenetic stand-off in a nutritional arms race’ is the evolutionary conflict in parental priorities – the father interested in passing on his genes through healthy offspring, and the mother focused on surviving the pregnancy and maintaining her future fertility. Beyond imprinting, other remarkable functions that junk DNA perform during reproduction include the random inactivation of one of the two X chromosomes in every female foetal cell – a function performed by the junk DNA gene called Xist (pages 128-135 and 82-86).

Just like the coding DNA, junk DNA is also susceptible to genetic and chromosomal disorders which the book exhaustively reviewed. One of the prominent diseases the author highlighted in this regard is the muscle disease myotonic dystrophy, a prime example of how the disruption of DNA regulatory mechanisms can lead to profound clinical disorders. The author pointed out that myotonic dystrophy is a dominantly inherited disease which results from an expansion in the number of junk DNA sequences: the DNA letters CTG are repeated beyond the normal number of 5-30. This abnormal expansion, she stressed, is sufficient to convert normal messenger RNA into a metaphorical ‘molecular sponge‘ which, by binding up cellular proteins, disrupts the regulation of ‘a whole number of other genes in the cell’. This is therefore a graphic example of how an abnormality outside the protein coding region of the gene could impair protein synthesis; the author indeed emphasised that the ‘pathological agent‘ in myotonic dystrophy is not a mutated protein but a mutated messenger RNA. The book also reviewed several other genetic disorders that arise from a similar mechanism, for example Friedreich’s ataxia, fragile X syndrome, and facioscapulohumeral muscular dystrophy (pages 8-11, 18-23, 231-232 and 283-285).

Beyond disruption of messenger RNA, there were several other disease-causing mechanisms related to junk DNA that the book examined. In this regard, some of the most fascinating are the chromosomal deletions that manifest as different clinical syndromes depending on whether the deletion affects a maternally or a paternally imprinted chromosome. To illustrate this intriguing phenomenon, the author cited the examples of Prader-Willi and Angelman syndromes – contrasting disorders that result from the same deletion in chromosome 15, and Beckwith-Wiedemann and Silver-Russell syndromes – distinct diseases which arise from the same deletion in chromosome 11. Other disease-causing mechanisms related to junk DNA are long non-coding RNA mutations which may result in disorders such as prostate cancer, Alzheimer’s disease, and neuropathic pain; and centromere dysfunction which may contribute to Down’s, Edward’s, and Patau’s syndromes – trisomy disorders in which cells have three instead of two chromosomes (pages 106-112, 136-141 and 75-78).

 

A striking feature of junk DNA is the remarkable range of important biological functions it coordinates, and the book descries several of these in detail. One such critical role the book explored occurs during cell division when stretches of junk DNA serve as ‘attachment points‘ for the spindle apparatus that pulls pairs of chromosomes towards either end of the cell. Another impressive example is the way junk DNA coordinates embryonic limb development by regulating the strategic HOX genes – a function that is subserved by long non-coding RNA. Other compelling functions of junk DNA include its role in limiting the life span of messenger RNA – a role it carries out either by making them double stranded, or by labelling them for destruction using microRNAs and small interfering RNAs. Beyond its primary biological roles, the author also noted that junk DNA has forensic utility in the form of small sized repetitive units called ‘simple sequence repeats‘; these account for 3% of the human genome and are used as DNA fingerprints to identify perpetrators and victims of crimes and massacres, and to exonerate people incarcerated for offences they did not commit (pages 64-67, 255-257 and 45).

 

Opinion

Junk DNA is a relatively new concept which this book has exhaustively explored. The author has gone to great lengths to simplify what is clearly a complex subject. The major content of the book is highly academic, but the author’s simple prose, and her use of several illustrations, go a long way to make the concepts accessible to the lay reader. The author’s use of useful and memorable metaphors greatly helped to explain the subjects she discussed. Perhaps in an effort to simplify the subject, the narrative is occasionally repetitive. The exhaustive text however covers the details necessary for appreciating the idea of junk DNA, and it emphasises their relevance, not only to health and disease, but to human development and criminology.

Overall assessment

This is a very enlightening, even if very academically-oriented, book. It brings to public awareness many important concepts which will be novel for many people outside the field. The topic has far-reaching and significant consequences for healthcare and for society, and the author has graphically conveyed this. The book has highlighted the wide-ranging significance and applications of junk DNA, and I recommend it to all doctors.

Book details

Publisher, Place, Year: Icon Books, London, 2015
Number of chapters: 20
Number of pages: 340
ISBN: 978-1-84831-915-8
Star rating: 4
Price: £8.19