Junk DNA

Junk DNA: A Journey Through the Dark Matter of the Genome

NESSA CAREY
Copyright Date: 2015
Pages: 360
https://www.jstor.org/stable/10.7312/care17084
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  • Book Info
    Junk DNA
    Book Description:

    For decades after the identification of the structure of DNA, scientists focused only on genes, the regions of the genome that contain codes for the production of proteins. Other regions that make up 98 percent of the human genome were dismissed as "junk," sequences that serve no purpose. But researchers have recently discovered variations and modulations in this junk DNA that are involved with a number of intractable diseases. Our increasing knowledge of junk DNA has led to innovative research and treatment approaches that may finally ameliorate some of these conditions.

    Junk DNA can play vital and unanticipated roles in the control of gene expression, from fine-tuning individual genes to switching off entire chromosomes. These functions have forced scientists to revisit the very meaning of the word "gene" and have engendered a spirited scientific battle over whether or not this genomic "nonsense" is the source of human biological complexity. Drawing on her experience with leading scientific investigators in Europe and North America, Nessa Carey provides a clear and compelling introduction to junk DNA and its critical involvement in phenomena as diverse as genetic diseases, viral infections, sex determination in mammals, and evolution. We are only now unlocking the secrets of junk DNA, and Nessa Carey's book is an essential resource for navigating the history and controversies of this fast-growing, hotly disputed field.

    eISBN: 978-0-231-53941-8
    Subjects: Ecology & Evolutionary Biology, Biological Sciences, Developmental & Cell Biology

Table of Contents

  1. Front Matter
    (pp. i-vi)
  2. Table of Contents
    (pp. vii-viii)
  3. Acknowledgments
    (pp. ix-x)
  4. Notes on Nomenclature
    (pp. xi-xiv)
  5. An Introduction to Genomic Dark Matter
    (pp. 1-6)

    Imagine a written script for a play, or film, or television programme. It is perfectly possible for someone to read a script just as they would a book. But the script becomes so much more powerful when it is used to produce something. It becomes more than just a string of words on a page when it is spoken aloud, or better yet, acted.

    DNA is rather similar. It is the most extraordinary script. Using a tiny alphabet of just four letters it carries the code for organisms from bacteria to elephants, and from brewer’s yeast to blue whales. But...

  6. 1. Why Dark Matter Matters
    (pp. 7-12)

    Sometimes life seems to be cruel in the troubles it piles onto a family. Consider this example. A baby boy was born; let’s call him Daniel. He was strangely floppy at birth, and had trouble breathing unassisted. With intensive medical care Daniel survived and his muscle tone improved, allowing him to breathe unaided and to develop mobility. But as he grew older it became apparent that Daniel had pronounced learning disabilities that would hold him back throughout life.

    His mother Sarah loved Daniel and cared for him every day. As she entered her mid-30s this became more difficult because Sarah...

  7. 2. When Dark Matter Turns Very Dark Indeed
    (pp. 13-24)

    The astonishing percentage of the genome that didn’t code for proteins was a shock. But it was the scale of the phenomenon that was surprising, not the phenomenon itself. Scientists had known for many years that there were stretches of DNA that didn’t code for proteins. In fact, this was one of the first big surprises after the structure of DNA itself was revealed. But hardly anyone anticipated how important these regions would prove to be, nor that they would provide the explanation for certain genetic diseases.

    At this point it’s worth looking in a little more detail at the...

  8. 3. Where Did All the Genes Go?
    (pp. 25-36)

    On 26 June 2000, it was announced that the initial draft of the sequence of the human genome had been completed. In February 2001, the first papers describing this draft sequence in detail were released. It was the culmination of years of work and technological breakthroughs, and more than a little rivalry. The National Institutes of Health in the USA and the Wellcome Trust in the UK had poured in the majority of the approximately $2.7 billion¹ required to fund the research. This was carried out by an international consortium, and the first batch of papers detailing the findings included...

  9. 4. Outstaying an Invitation
    (pp. 37-46)

    Every British schoolchild knows the date 1066. It’s the year that William the Conqueror and his troops from Normandy in what is modern-day France invaded England. This wasn’t some temporary raiding party. The invaders stayed, brought their families over and expanded in numbers and influence. They ultimately assimilated, becoming an integrated part of the English political, cultural, social and linguistic landscape.

    Every American schoolchild knows the date 1620. It’s the year that theMayfloweranchored at Cape Cod, triggering the great wave of European migration and settlement to North America. Like the Normans in Britain over 500 years before them,...

  10. 5. Everything Shrinks When We Get Old
    (pp. 47-62)

    The movieTrading Places, starring Dan Aykroyd, Eddie Murphy and Jamie Lee Curtis, was a huge hit in 1983, grossing over $90 million at the US box office.¹ It’s a convoluted comedy but the premise behind it is the exploration of genes versus environment. Is a successful man successful because of intrinsic merit or because of the environment in which he is placed? The movie comes out firmly on the side of the latter.

    A similar phenomenon can happen in our genomes. An individual gene may perform a relatively innocuous role, helping a cell keep on keeping on, so to...

  11. 6. Two Is the Perfect Number
    (pp. 63-78)

    One cell becomes two; two become four; four become eight and, to quote fromThe King and I, ‘et cetera, et cetera, and so forth’¹ until there are over 50 trillion cells in a human body. Every time a human cell divides, it has to pass on exactly the same genetic material to both daughter cells as it contains itself. In order to do this, the cell makes a perfect copy of its DNA. This results in a replicate of each chromosome. The two replicates stay attached to each other initially, but then are pulled apart to opposite ends of...

  12. 7. Painting with Junk
    (pp. 79-96)

    In a twelve-month period from 2011 to 2012, 813,200 babies were born in the UK.¹ Using the rates quoted in the previous chapter, we can estimate that nearly 1,200 of these babies had Down’s Syndrome, around 270 had Edward’s Syndrome and just under 120 had Patau’s Sydrome. That’s a very small number of cots in a nursery of over three-quarters of a million babies. This is consistent with the concept that having too many copies of a chromosome is very damaging: in general we would not expect high survival rates when it occurs.

    Which makes it all the more surprising...

  13. 8. Playing the Long Game
    (pp. 97-112)

    For quite a few years, Xist was considered an anomaly, a strange molecular outlier with an extraordinarily unusual impact on gene expression. Even when Tsix was identified, it was possible to think that junk RNAs were restricted to the vital but unique process of X inactivation. It is only in recent years that we have begun to recognise that the human genome expresses thousands of this type of molecule, and that they are surprisingly important in normal cellular function.

    We now categorise Xist and Tsix as members of a large class known as the long non-coding RNAs. The term is...

  14. 9. Adding Colour to the Dark Matter
    (pp. 113-124)

    In biology, the questionWhat does something do?is almost always followed by the questionHow does it do it?. We know what long non-coding RNAs are, and we know at least some of what they do – they regulate gene expression. So the perfectly reasonable question is, how do they do that?

    There’s not going to be one answer to that question. There are thousands and thousands of long non-coding RNAs produced from the human genome, and they almost certainly won’t all work the same way. But certain themes are starting to emerge.

    One of the most important themes...

  15. 10. Why Parents Love Junk
    (pp. 125-144)

    One of the first Bible stories learnt by children raised in the Judaeo-Christian faiths is the creation tale from Genesis. In this story, God creates the earth and the heavens and all that is in them, and finally he creates Adam and Eve. After that, peopling the earth is down to those two and their descendants, with no further divine intervention apart from the obvious exception in the Christian tradition at the start of the New Testament.

    The strong grip of the Adam and Eve story perhaps drives or possibly reflects our ingrained acceptance of a simple piece of biology....

  16. 11. Junk with a Mission
    (pp. 145-156)

    It’s quite possible that the most wonderful and compelling aspect of biology is its glorious inconsistency. Biological systems have evolved in magnificently creative ways, usurping and repurposing processes for completely new uses wherever possible. It means that almost every time we think a theme is emerging, we find exceptions. And sometimes it can be very difficult to unravel which is the norm and which the exception.

    Let’s take junk DNA and non-protein-coding RNAs. Based on pretty much everything we have seen so far, it would be perfectly reasonable to develop a hypothesis along the following lines:

    When junk DNA encodes...

  17. 12. Switching It On, Turning It Up
    (pp. 157-174)

    With a mere $1,700,000 price tag, the Bugatti Veyron is the world’s most expensive production road car. It’s hard to be sure what the cheapest car is, although the Dacia Sandero probably has a good claim to this honour, at about 1 per cent of the cost of the Veyron. But both cars have a number of things in common, and one of these is that each needs to be switched on before you can go anywhere. If you don’t activate the engine systems, nothing will happen.

    Our protein-coding genes are the same. Unless they are activated and copied into...

  18. 13. No Manʹs Land
    (pp. 175-184)

    When we think about the First World War, the prevailing image many of us have is probably of men in trenches. Opposing armies dug into the muddy landscapes for the ultimate exposition of war as months of boredom, punctuated by moments of acute terror.¹ The trenches occupied by the armies were separated by stretches of terrain that were not under the control of either combatant. These stretches were ‘No Man’s Land’, and could be as narrow as a couple of hundred metres, or over a kilometre wide. At night, the soldiers would creep out of the trenches for reconnaissance, to...

  19. 14. Project ENCODE - Big Science Comes to Junk DNA
    (pp. 185-200)

    If you ever find yourself far from city lights, on a cloudless night with no moon, grab a blanket and lie on the ground and look up at the stars. It’s one of the most wonderful sights imaginable, and quite breathtaking for anyone who spends their life in a city. The glints of silver in the dark blanket of the heavens seem too many to count.

    But – if you have access to a telescope, you realise that there is so much more in the firmament than you can detect with the naked eye. There are details like the rings...

  20. 15. Headless Queens, Strange Cats and Portly Mice
    (pp. 201-218)

    The ENCODE consortium identified a daunting abundance of potentially functional elements in the human genome. Given the huge numbers, it’s hard to define a sensible strategy for deciding which candidate regions to experiment on first. But the task may not be quite as difficult as it seems, and that’s because, as always, nature has decided to point the way. In recent years scientists have begun to identify human diseases that are caused by tiny changes to regulatory regions of the genome. Previously, these might have been dismissed as harmless random variations in junk DNA. But we now know that in...

  21. 16. Lost in Untranslation
    (pp. 219-236)

    There are few crimes lower than deliberately hurting a child. In many countries, staff in emergency departments are trained to look for patterns of unexplained injuries including fractures in babies and toddlers. Often such a medical history will result in children being taken into care, little or no parental access, and ultimately prosecution and possibly imprisonment of one or both parents.

    Protection of a child is of course paramount. But imagine the nightmare for parents if this happens to them and they are entirely innocent, because the fractures are due to an undetected medical condition.¹ Although the number of such...

  22. 17. Why LEGO is Better Than Airfix
    (pp. 237-254)

    Most children, and quite a few adults, enjoy making models. There are various ways of doing this but let’s just look at the extremes. One of the most popular formats in the UK for over 30 years was the Airfix kit. Small plastic parts specific to an aircraft, ship, tank or just about anything else you can think of (Bengal Lancer, anyone?) were supplied with detailed instructions. The user glued the parts together, painted them, applied transfers and admired the finished article for years after.

    At the other extreme is that universal Danish toy of which I am so fond,...

  23. 18. Mini Can Be Mighty
    (pp. 255-270)

    Perhaps because we are quite large animals, we tend to be most impressed by other large animals. And that’s OK. After all, a big cat such as a jaguar is an impressive creature. We also tend to be impressed because the jaguar is a hunter, a top carnivore. An ant, by comparison, looks rather puny, even if it’s one of the Central and South America species of army ant. Sure, there is a certain gory charm in an insect with jaws so large and strong you can use them to hold the sides of a wound together. But it’s still...

  24. 19. The Drugs Do Work (Sometimes)
    (pp. 271-282)

    Billions of dollars are spent every year by companies trying to create new drugs to treat human diseases. They hope to find ways to tackle unmet medical needs, a situation that is becoming ever more urgent with the increasing age profile of the global population. The breakthroughs in the understanding of the impact of junk DNA on gene expression and disease progression are triggering a slew of new companies seeking to exploit this field. Specifically, most of the new efforts are in using non-protein-coding RNAs as drugs in themselves. The basic premise is that junk RNA – long non-coding, smallRNAs...

  25. 20. Some Light in the Darkness
    (pp. 283-288)

    As we near the end of our wanderings through the darker regions of our genome, the more alert reader may remember that we haven’t addressed the mystery of one of the human disorders first encountered at the beginning of this book. This condition is the cumbersomely named facioscapulohumeral muscular dystrophy, or FSHD. This is the condition in which there is wasting of the muscles of the face, shoulders and upper arms.

    It occurs when patients inherit a smaller number of a particular genetic repeat on one of their copies of chromosome 4. Even quite a few years after the mutation...

  26. Notes
    (pp. 289-328)
  27. Appendix: Human Diseases Cited in the Main Text, in Which Junk DNA Has Been Implicated
    (pp. 329-332)
  28. Index
    (pp. 333-340)