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

by Nessa Carey

An exploration of the once-ignored portion of our DNA and the role it plays in our bodies, from the author of The Epigenetics Revolution.

For decades after the identification of the structure of DNA, scientists focused only on genes, the regions of the genome that contain codes to produce 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 several 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.

“Engaging, informative, and humorous.”—Sharon Y. R. Dent, University of Texas MD Anderson Cancer Center

“A cutting-edge, exhaustive guide to the rapidly changing, ever-more mysterious genome.”—New Scientist

Genres: Science, Nonfiction, Biology, Genetics, Evolution, Medicine, Popular Science

356 pages, Kindle Edition

First published March 5, 2015

About the author

Nessa Carey has a virology PhD from the University of Edinburgh and is a former Senior Lecturer in Molecular Biology at Imperial College, London. She worked in the biotech and pharmaceutical industry for thirteen years and now splits her professional time between providing consultancy services to some of the UK's leading research institutions, and training people around the world in how to create benefits for society from basic research. She lives in Norfolk and is a Visiting Professor at Imperial College.

Reviews

[Left Coast Justin · Rating 4 out of 5]

This is quite the treasure trove of information for people who are fairly well-versed in molecular biology -- the author doesn't spend a lot of time addressing the needs of neophytes. (By "well-versed," I mean understands both the structure and the role of histones; familiar with telemeres and the differences between rRNA and tRNA etc.)

Many of us are familiar with false pregnancy, or pseudocyesis. This is a desire for, or belief in, one's pregnancy that is so strong that many symptoms of pregnancy actually begin to manifest in the affected person. (I say 'person' and not 'woman' because this sometimes affects men, too, up to and including lactation.) This author has no time for that particular flavor of human frailty. Instead, she dives right into the fascinating topic of hydatidiform pregnancy, which has the advantage of a clearly-assignable molecular cause. In this case, a healthy sperm runs the gauntlet and penetrates an egg, but for some reason this egg is missing its nucleus -- no 23 mama chromosomes, no gene mixing, and indeed no chance of creating a child. I can't help but think of those gormless white pods inside a "seedless" watermelon.

I will pause here to acknowledge that life isn't fair, particularly to women. Because this egg, while genetically worthless, still follows the script and implants itself into the uterus. The uterus, sensing something amiss, becomes red and inflamed and launches a sortie of morning sickness so awful that even the hard-hearted OB-GYN realizes something is wrong, and removes the errant non-embryo. (Left on its own, it will spontaneously abort after five months or so of maternal agony.)

Okay, this book is not for beginners, which means I'm just getting started. Roll up your sleeves....As we're aware, once a sperm cell penetrates an egg, the egg responds by immediately pulling up the drawbridge, locking the doors and rendering itself off-limits to further suitors. But -- ooops -- in hyadatidiform eggs, that instruction set is missing along with everything else, and so, in principle, more than one sperm can penetrate. Which could actually be kind of nifty, because hey presto, with *two* sperm cells, we now have a full complement of 46 chromosomes with which to start building a new baby. Right?

If your instincts tell you this doesn't sound right, your instincts are good. More lightweight books talk about "the genetic code," by which they mean the ~2% of our DNA that actually does something, like generate proteins or mix things up during fertilization. This book focuses on the 98% called 'junk,' which is, of course, a complete misnomer. The science in this area is far behind the more common 'active' DNA, and the author is clear to point out when things are still speculative or unproven, to her credit.

Returning to our mystery: Did you know that mammals are the only known class of animals that have no means (Mayo Clinic aside) of asexual reproduction available to them? Now we have to zoom out from the microscopic world to the rough-and-tumble of evolution, where we observe the following:
1. Males' enthusiasm for sex has been known to cloud their judgement.
2. Women historically have paid a price for flirting with men they are not paired off with. (Which doesn't stop them from doing it, thank God.)
The bottom line is, men would have a lot more sex partners if women weren't so good at reckoning the societal cost, and women might be inclined to dump their current specimen if a better one were to show up. So a compromise of sorts has been reached: Women have developed excellent bullshit detectors that limit the number of partners men have, and women, once pregnant, are pretty much stuck with that kid for the duration -- it's not so easy to become un-pregnant (historically) and start over if a better match shows up. There is a molecular system in place to ensure that both parents are represented in the baby, and that Mom can't just shut things down if she finds another man who appears to be more inclined to change the litter box and give her foot massages.

Back to molecules: You might guess, quite reasonably, that the egg containing two sperm cell's worth of genetic material would be rejected wholesale, right off the bat. But it doesn't work that way. Instead, the wrongly-fertilized egg actually begins to grow for a while (at least, in experiments run in mice) before getting shut down. The same thing happens if clever scientists put the nuclei of two egg cells together into an egg. It all has to do with the way junk DNA methylates the histones (see Paragraph 1 of this review) to decide whose gene, Mom's or Dad's, is going to show up for this particular feature of this particular kid. Some of these mechanisms....it's complicated. But they don't act immediately, but only after a certain number of cell-division cycles, which is why the weird embryo takes a while to become unviable.

All of this, by the way, consumes about four pages of this 288-page book (not counting notes and references). The idea here is not to really review the book, but just to give you a flavor of the overwhelming fascination and complexity of molecular genetics. This would be a four-star book if the author were a bit more gifted with language and teaching. There's no room left in this review to show examples of confusing or downright-bad writing, but they are legion.

So many fascinating topics in this book! Back when I was heavily involved in pancreatic cancer for work, I learned about a drug called paclitaxel that "interfered with cell division," but that's all I knew. Now I've learned that there are special molecules that, during cell division, grab hold of a splitting chromosome (in a special spot, of course, within the 'junk DNA,' of course) and pull the two halves to opposite ends of the cell, and then releases them. Paclitaxel doesn't allow them to let go, and so they've got this long stringy junk attached to them when they're trying to connect with the other chromosomes to form a new cell. Another example: there are only two genes that determine whether we're male or female. (Eye color involves at least ten genes, for comparison.)

There are horrible birth defects that can be traced to a single base-pair error on a single gene. Do yourself a favor, if you read this, and skip the Google Image Search of the various syndromes listed here. No, I'm not going to list them.

I need to stop.

[Jamie Smith · Rating 4 out of 5]

I studied the C programming language, and one of the things that was stressed was the danger of null pointers. A pointer is a type of variable that points directly to a location in memory, so it is a fast and efficient way to access data. However, when you create one, if you forget to set it to an initial value, such as zero, it will have a random hexadecimal number representing whatever combination of ones and zeros happened to be at that memory location when the computer was turned on. If that random number points to a key area of the computer’s operating system or video memory, and you start writing to it, VERY BAD THINGS can happen.

Now think about DNA. It has over 3 billion base pairs, made up of only four different ‘letters,’ C, T, A, and G, which create amino acids which then create proteins. Now imagine that an error has crept into either the sperm or egg cell which have combined to create an embryo. Every one of the daughter cells resulting from cell division will have the same change. Errors involving a single base pair could cause serious consequences by changing which amino acids are created, thereby altering the start or end sequence of a protein string. If the defect causes the RNA to add base pairs from before the actual start of the string, or after its end, or if it causes the string to terminate early, the resulting protein would be non-functional. This means that a single mutation in one of the 3 billion base pairs could result in that baby not being able to make a specific protein, and VERY BAD THINGS can happen.

Scientists learn how it all works by studying what happens when things go wrong, and this book describes a number of horrifying genetic conditions, from Fragile X syndrome, to Lou Gehrig’s Disease, Burkitt’s lymphoma, Ohio Amish Dwarfism, and many, many more. It’s enough to make you lie in bed at night staring up at the ceiling wondering how any of us turn out more or less normal.

Want something else to worry about? Consider telomeres. We get one set of 23 chromosomes from our mother and one from our father, 46 total, each with a beginning and an end, for 92 in all. Telomeres are used to mark these ends, an important function because otherwise the ends of different chromosomes could get joined up, resulting in the creation of too much or two little of essential proteins, such as the ones that regulate cell division, which would greatly increase our chances of cancer. “The telomeric DNA is formed from repeats of the same six base pairs, TTAGGG, repeated over and over again. These stretch for an average of about 10,000 base pairs in total on each end of every chromosome in the umbilical cord blood of a newborn human baby.” (p. 49) However, the number of telomeres decreases every time the cell divides, so the longer we live, the greater the chance we will get cancer or something equally awful.

The key segments of the human genome were sequenced in 2001, although it was not one hundred percent sequenced until 2022. Many researchers had predicted they would find 50,000 genes, and some estimates were three times that, so it was a shock when the actual number was only about 24,000. However, at least 70 percent of our genes can fold into different configurations, producing multiple different proteins. Another surprise was that over 98 percent of the DNA in a human cell does not code for proteins at all, and thus was labeled ‘junk.’

Some of it truly is junk, consisting of sequences that found their way into our DNA far, far back in time. It must have been evolutionarily useful at some point, or it would have been weeded out. Over time its usefulness was lost, and since it was not harmful there was no pressure to remove it, and without that it could mutate freely, so by now those stretches of DNA are just random junk. There are some mechanisms in the DNA replication sequences that ensure this extraneous DNA remains suppressed, but long stretched of it are harmless anyway, just excess baggage passed down from very distant ancestors.

After the genome sequencing was completed, further research yielded interesting findings. Human proteins themselves are not especially large, and about the same size as those of flies or worms. “The only genomic feature that increased in number as animals became more complicated were the regions of junk DNA. The more sophisticated an organism, the higher the percentage of junk DNA it contains.” (p. 12)

Clearly, there must be method in this madness, and it is unfortunate that the name junk has stuck. Junk DNA performs a number of critical functions, which this book describes chapter by chapter. These include things like retrogenes, assisting protein sequence creation, non-protein coding RNAs, telomeres, centromeres, enhancers, promoters, epigenetics, 3D interactions, splicing, and insulators. I admit that I had some trouble following a few of the explanations, but the book has a number of good illustrations to show what is going on.

There are also has some surprising facts. In discussing stem cells, which can form any type of cell as needed, I did not know how energetic the process of red blood cell creation is. “The human body produces about 2 million red blood cells every second. That requires an awfully active stem cell population, in a pretty much constant state of cell division. This is one of the reasons why cancer rates rise with age. Our immune system usually does a good job of destroying abnormal cells, but the effectiveness of this surveillance declines as stem cells die off.” (p. 52)

And here’s a fun fact: “If you stretched out the DNA from one human cell it would reach for two metres, assuming you joined up the material from all the chromosomes. But this DNA has to fit into the nucleus of a cell, and the nucleus has a diameter of just one hundredth of a millimetre.” (p. 64)

Finally, something I had never heard before, “the two strands of DNA run in opposite directions.” (p. 79) So, the first chromosome from one parent is joined to chromosome twenty-three of the other.

I enjoyed this book, and learned a lot from it. To help illustrate her points the author uses lots of homey metaphors, such as toast and butter in explaining how one X chromosome is preferentially, but randomly, selected over the other. She has another book, on epigenetics, which I have added to my reading list.

[Rachel (Kalanadi) · Rating 4 out of 5]

Maybe a third of Junk DNA overlaps with the contents of Carey's previous book, The Epigenetics Revolution. This was most likely obvious to me because I read them so closely together. The overlap is not a bad thing at all, but it made me notice that even though Junk DNA is more readable because Carey discards references to gene names and other very technical nomenclature, I actually preferred the approaches to explaining experiments and processes in the Epigenetics Revolution. Sometimes I really craved those names because without them passages seemed almost too vague or abstract. (This is my preference, though, and not a criticism of Junk DNA.)

Junk DNA gets very into the nitty gritty of an expanded set of "junk DNA" examples that haven proven (or strongly promise) to have incredible consequences on gene expression and function. There's a lot more going on in our genome than it appears anyone expected even a decade or so ago. This is just incredibly exciting!

Things I now completely love about Nessa Carey: bizarre and whacky analogies that really do help* and a great sense of humor. Both books I've read by her feel warm and human, like she's having a conversation with the reader, and I think it really helps to make any technical or dry passages consumable. I wish Neil deGrasse Tyson or Mary Roach would write more technical books, because I think that would be the same combo of "great personality" and "beyond the basics" that I like Carey's work for.


(*Worth noting, perhaps, that Junk DNA does seem to rely more heavily on analogies than The Epigenetics Revolution. Great for a lay audience, but once again sometimes I missed knowing the exact names and terms for a few things.)

[Jasmine · Rating 3 out of 5]

At last, this day has come! It has been a long journey indeed...

Reasons why I loved this book:
1. The biology was interesting, to say the least. A reminder that biology is worth more than the tedious syllabus that A-Level provides.
2. It was comprehensive, accessible, translating some complex features of the human genome into Standard English. It was also fun to see the writings of a scientist that actually seemed to relate to the wider reader and whose writing style was not as pompously attached to the sound of their own voice (Dawkins-style).

Reasons why I hated this book:
1. Much, much too comprehensive. The reason why I started the book in September 2017 and finished it in January 2018, almost half a year of pain and questioning why I even bothered. Slightly ironic, isn't it, that Carey wrote a book about the 98% of our DNA that is classified as 'junk', when almost the same percentage of her words could be classified as that also. If I hear one more analogy about Bible stories or goddamn Lego, I'll destroy my own neurones as I bang the book on my head in frustration. Whenever Carey thought her dear reader might find it too complex to read the actual name of an enzyme or a protein (a name!), she conveniently left it out. Oh, if only I could do the same in my Biology layer tests!
2. The book went nowhere. It's one of those sorts of books that wish to present a paradigm-shifting idea, when the idea was sort of obvious in the first place. Or if not obvious, the fact that junk DNA is not in fact junk, the idea was reinforced so strongly, reiterated so many times and given no room for counterargument whatsoever that it makes you want to cry tears of boredom. It sort of dabbled here and there, but went nowhere. Every exploration into a different feature of junk DNA started and ended with here's another reason why junk DNA is not junk, and then (spoiler!) the book concluded with (here I paraphrase) "we don't know if any parts of junk DNA are actually junk, but the bits that aren't junk aren't but are actually useful". Interesting biology, but mind-bogglingly repetitive. I admire Nessa Carey for not getting bored writing it.

[J.M. Lee · Rating 4 out of 5]

A self-explanatory title, but not quite: the object of this book is to reveal the many ways in which so called “junk” DNA is nothing of the sort. About 98% of human DNA does not code for protein production, and this has traditionally been assigned the status of junk. But there are many ways in which such DNA can be involved in crucial ways to the healthy functioning of cells. The author takes as balanced a view as possible of issues causing controversy among the specialists, neither attributing function to all junk DNA nor assuming its total irrelevance. They investigate the functionality discovered to date in a way that is accessible to the general reader. The relation of “junk” to epigenetics features prominently. Epigenetics is modifications of DNA or proteins around it which “don’t change the sequence of a gene” but “alter the likelihood that a specific gene will be expressed.” The author shows the importance of “junk” DNA and epigenetics by tracing out the relation between their malfunction and some serious human diseases, such as myotonic dystrophy, fragile X syndrome, and Friedreich’s ataxia.

There are a lot of illustrative analogies. For example, when discussing telomeres, which occur at the ends of chromosomes, and protect them from degradation, we are told, “Are you wearing shoes with laces? If so, have a look at those laces. At either end there is a little cap made from metal or plastic. This is called the aglet, and it stops the lace from unravelling and fraying.” The analogy with biochemically induced fraying of our chromosomes makes that process accessible to the non-scientist. Sometimes the analogies are less clearly related to the biochemical processes described, as when a result of “frame shifting” in the reading of a protein coding region of DNA due to mutation of junk DNA results in the malfunction of an important protein, as occurs with Duchenne muscular dystrophy. The analogy for the malfunction of the protein is a mattress with too short springs (because it is not so good at absorbing shocks as one with springs extending all the way from the base to the top). To my taste this is a little too much analogy for its own sake. More generally I am of two minds about the pedagogical value of easily visualised analogies, since I have seen research demonstrating children learn scientific and mathematical concepts better when taught directly in the abstract, and presumably the mostly adult readers of this book would do so also. It is, however, an engaging approach, and will possibly keep some readers reading when they would otherwise have thrown the book aside.

There is no escaping some technical detail, however, and the author provides as much of this as the intelligent non-scientist can reasonably be expected to absorb. If you persevere you will learn a lot of the genetics and epigenetics that might be encountered in an introductory Biology course. Having read the cellular biology and genetics sections of a first year Biology textbook a few months before reading this, much of it was familiar, though slightly less technical.

If much of what you have just read is a bit confusing, you will find it makes more sense with more context, and sequentially developed, as it is in the book. For anyone interested in popular science, especially genetics and epigenetics, and possibly even for scientists working in other fields, I would strongly recommend this book. It is engaging, informative, and important.

I’ll conclude with one fascinating fact in the book: the protein coding region of the human genome is not much larger than that for C. elegans, a microscopic worm. Of course, as the author discusses, the complexity of the human organism is clearly not directly related to the size of our protein coding DNA, but human hubris can always do with a good knock on the head. In terms of coding DNA, we’re not so special after all.

[Nicky · Rating 4 out of 5]

I’ve read Nessa Carey’s work before, in The Epigenetics Revolution, so I had high hopes for this — especially because it involves a lot more discussion of epigenetic modification of gene expression, and because genetics in general is something that fascinates me. If this is an interest of yours, then this will definitely work for you; I didn’t feel like it repeated the basics too much, but at the same time, it was perfectly readable for anyone at a lower level. I think so, anyway; it’s hard for me to judge now, after so much reading and now study of genetics! I can definitely say that if you know the basics about genetic inheritance and the central dogma of biology, this should work for you.

It’s also very readable and enjoyable; I’ve read some books which unfortunately manage to make genetics boring, even for me, but Carey’s isn’t one of them. This is one of the books I have no doubt I’ll keep entertaining friends and families with random information from — did you know? Did you know?

Originally posted here.

[Elentarri · Rating 4 out of 5]

Junk DNA: A Journey Through the Dark Matter of the Genome discusses the uses and functions of the 98% of DNA that doesn't code for a specific protein (i.e. "Junk DNA"). The topics covered in this book include retrogenes, DNA/RNA repeats, protein sequences, non-protein coding RNAs, telomeres, enhancers, promoters, epigenetics, 3D interatctions, splicing, insulators, centromeres and examples of the various diseases and disorders that can occur when "junk DNA/RNA doesn't function properly. The information covered in the book is very interesting and mostly easy to understand for the non-scientist and non-genetic specialist. There is a fair amount of technical detail, but it is impossible not to have technical details in a book that discusses the biochemistry of cell function and DNA expression. The inclusion of illustrative analogies and diagrams helps the reader picture the cellular functions and concepts. A rather nice overview of a complex subject.



NOTE: Author has irritating habit of insisting that the human appendix has no useful function and is a relic of evolution. This is an outdated idea. For those interested, the appendix:.
(1) functions as a safe-haven for useful/friendly bacteria when illness flushes those bacteria from the rest of the intestines.
(2) has more recently been identified as an important component of mammalian mucosal immune function. The appendix helps in the proper movement and removal of waste matter in the digestive system, contains lymphatic vessels that regulate pathogens, and might even produce early defences that prevent deadly diseases.

[Robert · Rating 3 out of 5]

Carey follows up her book on epigenetics (essentially the effects of parts of DNA that aren't the base-pairs that make up genes) with another that looks at the 98% of your DNA that doesn't code for proteins, generally referred to as "junk" because it was believed it had no biological function.

This model, that all you need to understand cellular life is a list of the protein-coding segments of DNA, has completely colapsed. Numerous DNA sequences that have nothing directly to do with protein manufacture have been found to be essential to the proper functioning of cells in complex life. You can learn about many of them here, in a very clear, fair and balanced way.

I have become interested in the actual chemistry of the various processes Carey describes in her first two books at the level of metaphor. I'm not sure where to find out about that, short of an academic text. Similarly, although the references to the academic literature are all present and correct, Carey glosses over the details of the experiments used to reach the conclusions expressed. A book about that would go down well, too.

Carey has a book about gene editing and CRISPR - I'm looking forward to reading that, too.

[Orla · Rating 5 out of 5]

6/5. maybe the best biology book i’ve ever read?? any interesting topic around genetics that i could think of was included. X-inactivation, telomeres and aging, etc etc etc. will it take me the rest of the year to truly understand what’s going on ? yeah probably. but still 6/5⭐️⭐️⭐️⭐️⭐️⭐️

[Vinayak Hegde · Rating 4 out of 5]

Junk DNA turned out to be one of the most fascinating books I’ve read about genetics - challenging the very notion of “junk.” The author does a brilliant job of showing that what was once dismissed as useless filler in our genome is, in fact, deeply involved in regulating how life works.

One of the most striking parts of the book for me was learning how redundant DNA sequences—once thought to be irrelevant - play a big role in controlling which genes are expressed, when, and in what amounts. This connects directly to health and disease, as these non-coding regions often determine susceptibility to various genetic conditions. The discussion on telomeres - the protective caps at the ends of chromosomes - was eye-opening. Their length acts almost like a biological clock, determining how many times a cell can divide, and thus influencing aging and longevity.

I also appreciated the section on histones—the protein “spools” around which DNA wraps—and how this packaging (called the nucleosome structure, with DNA wrapped around histone octamers) controls which parts of the DNA are accessible for transcription. This interplay is crucial for regulating gene expression and has implications for cancer research and epigenetics. The book also delves into fascinating molecular players like Xist and Tsix, two non-coding RNA molecules that control X-chromosome inactivation—a mechanism that ensures females (with two X chromosomes) don’t produce double the proteins encoded on the X chromosome compared to males.

One tidbit, I found particularly intriguing explained how antibiotics like tetracycline and erythromycin exploit these processes by targeting bacterial ribosomes disrupting their protein production while sparing human ribosomes. The difference between them is due to natural evolution over millions of years. Also interesting was the section on mitochondria - the “powerhouses” of the cell - which have their own genome, a remnant of their origin as free-living bacteria before they became symbiotic partners within our cells. Finally, I was fascinated by the role of small RNAs - tiny RNA molecules that can silence or activate genes, adding yet another layer of complexity to gene regulation.

Overall, Junk DNA is a brilliant and highly readable exploration of the parts of our genome we once thought were useless (compared to the parts that encode for protein) but now recognize as central to life itself. I loved how the author used various analogies from our daily life to illustrate complex interactions and concepts. It made me appreciate how much of cellular biology is about regulation, timing, and subtle control - not just the genes themselves.

[Charlene · Rating 4 out of 5]

Great examination of just what "junk" DNA can do.

When humans don't understand something, they often label it in such a way to suggest it does not matter. Labeling the non-coding portion of DNA as "junk" is just such a case. Carey provides the reader with myriad evidence about the wonderful role junk plays in helping cells and larger organisms, such as humans, function. Junk regulates DNA in many ways that are helpful and some ways that are not so helpful. Carey gives a pretty thorough survey of the dynamic nature of junk.

[Michiel · Rating 4 out of 5]

Leaving the hard core genetics and molecular biology field in favor for computer science, I was nearly forgotten how fascinating the living cell can be. Carey sketches the clockwork of living beings, painting the proteins as merely the dumb muscle and DNA and RNA the true main actors.

[Brian Clegg · Rating 4 out of 5]

What grabs the reader fairly early on in Junk DNA is just how wonderfully complex and sophisticated the biological machinery in our cells is. As a non-biologist, I found that reading her description of the way that the cellular mechanisms pull the two copies of a chromosome to opposite sides of the cell, for instance, absolutely riveting. But it's not all superbly functioning miniature marvels: Nessa Carey also explores the many ways that these genetic mechanisms can go wrong. Anyone who ascribes the complexity of biological systems to a designer needs to contemplate just what a messy, over-complex and ad-hoc design has emerged.

I really hadn't though of there being a mechanism for separating copies of chromosomes before - and I think this is the beauty of Carey's book. Us non-biologists have some vague idea of how cells split or proteins are assembled from the genetic 'instructions', but there's a whole host of mechanisms required to go from an apparently simple concept to making it happen, and this really opens up in Junk DNA.

I mentioned how things go wrong. As genetic medical conditions are often a key to unlocking the secret of a cellular mechanism, there is a lot about genetic failures here, some very distressing - I'm personally not a great enthusiast for things medical (I can't even watch Casualty, let alone 24 Hours in A&E), but in this context it at least wasn't gratuitous.

Of course, as the name suggests, at the heart of the book are all the bits of our DNA - the vast majority of the content of our chromosomes - that aren't genes. In her previous book, The Epigenetics Revolution, Carey had already introduced us to some of the workings of what was once referred to as 'junk DNA' - specifically how parts of it turn various genes on and off, effectively acting as the controls that work the mechanisms specified by our genetic blueprints - but in this new book we see many more processes, capabilities, wonders and failings of the super-genetic parts of the system.

I do have a couple of niggles. This is a topic that lends itself to metaphor and simile - I did it without even noticing in the previous paragraph, but Carey plunges into metaphorical mode at the slightest opportunity, and some of her similes are a little painful - when she brings in the movie Trading Places or a Bugatti Veyron, for instance, the process seems forced. (Even the subtitle is a metaphor of sorts.) Also slightly irritatingly, several times she refers to the human appendix as having no function - if she'd read my Universe Inside You, she'd have known that this concept, like classifying all DNA that doesn't code for proteins as junk, went out some time ago (the appendix does have a useful function as a kind of respite centre for friendly bacteria from the wild conditions in the stomach).

The other issue, is that we end up in Rutherford's 'all science is either physics or stamp collecting' territory. While some the mechanisms themselves are truly fascinating, when the reader gets bogged down in the detail it can begin to seem that there is far too much cataloguing and not enough narrative. Carey has usefully responded to reviews of the previous book by often moving the name of a gene into a footnote, but it doesn't prevent the feeling of drowning in labels when you read something like:

Where C is followed by G in our genome, the C can have a small modification added to it. This is most likely to happen in regions where this CG motif is present in high concentrations. The large number of CCG repeats in the Fragile X expansion provide exactly this environment.

This is by no means the most concentrated example of labellitis, and typical of quite a lot of the text. In the end I was happy to think 'It goes with the territory, live with it.' There is still so much fascinating material in here that it is well worth ploughing through the biological wordfest.

[Sara · Rating 4 out of 5]

I liked this book, though I enjoyed the Epigenetic Revolution much better. This one is along the same lines, but it gets pretty technical. I had to start and stop a lot. Still, I'm a fan of the author's explanatory prose and unlike another reader here I did mostly appreciate the analogies.

I wonder if this book would have read better if they opened it up with a narrative about a case study involving the chapter's topic rather than sticking it in after the explanation or between them. I mostly appreciated the pictures though I had re read a few of them.

I was left with a couple questions- in one section the author mentions one set of genes from a parent that are activated during development, which led me to wonder about heterozygosity, incomplete dominance, etc. Still I learned quite a bit and I feel like I have a much better understanding of gene regulation and junk DNA even if it's a newly developing science.

Would recommend this one if you have a passion for genetics and enjoy tackling a somewhat more challenging read.

[Vibhu AV · Rating 5 out of 5]

I used to compare the complexity of the physical universe and of our brain, and concluded that our brain is more complex of the two. After reading this book, I realized that our genome and genetics—how genes interact, how non-coding parts of the genome (called junk DNA by a definition adapted in this book) influence gene expression, not just by epigenetic but by directly interfering with genes’ production of proteins—is as complex, if not more, than our brains! What we know about genes (DNA - > RNA -> proteins, called Central Dogma in molecular biology) is just the tip of the iceberg. The close to 98% of the DNA whose functions we didn’t know, and termed them as junk DNA, in fact plays a very convolutedly complex and huge role in overall genetics, of which we know so little, making me think that genetics is more complex than brain, consciousness, etc.

In this book, Nessa Carey uses diseases as a vehicle to describe how the so called junk DNA plays an active role in modifying, fine-tuning, even turning off or on some genes or even entire chromosomes (for example, the extra X-chromosome in women resulting in Barr bodies) and thereby influencing protein production. She touches upon possible pharmaceuticals based on understanding the role of junk DNA. While this method of using diseases to convey her messages is effective, I suspect that junk DNA are not just troublemakers, instead they are as central as the coding parts of chromosomes, thereby rendering the Central Dogma not so central!

[Himanshu Bhatnagar · Rating 5 out of 5]

A fascinating journey into the mysteries of our DNA. "Junk" DNA has come into focus only over the last couple of decades and there is still a lot we don't know about it, but Nessa Carey presents all that we have learned in a very engaging and lucid format that shouldn't be hard to grasp, even for someone with no understanding about genetics: by contrast, her earlier work on epigenetics was more technical. That is not to say that this book is dumbed down: it is more a facet of the topic she covers. From centromeres to telomeres to lncRNA to siRNAs, Carey covers it all and still manages to keep the reader both intrigued and engaged.

A tour de force from an author who has joined my 'favorite authors' club!

[skylie jo antle · Rating 4 out of 5]

loved the metaphors

[Nilesh Jasani · Rating 4 out of 5]

Our DNA, as we have been told since forever, is a naturally evolved script. AI models aside, we are trying to decipher what its complex web result in through human-language categories. Ms. Carey is the best author we have on making this complicated science somewhat understandable to non-specialists. Junk DNA is not her best work in some ways, but still a must-read for all interested in the topic.

Let's continue with the script analogy while discussing this book that excels in providing analogies liberally. Human languages, like say the extinct Harrpan language, are evolved constructs without strict rules, unlike designed languages like those used in computer programming. Later day linguists use various categories - nouns, verbs, adjectives, etc. - to understand the structures of these languages. Still, these categories do not wholly explain all nuances or usages, let alone the faults and the future variations.

Our DNAs have one clear category - the protein-coding genes. The remaining 98% of our DNA base pairs' roles have been relatively far more unclear, with some brandishing them all as "junk." The author comprehensively asserts that the rest have significant and critical functions in how we end up biologically, mostly through their influences on the expressions of protein-coding genes.

The details are mind-boggling, as there are in any languages, and here we are talking about a biological, evolutionary script. Through telomeres, centromeres, introns, enhancers, enhancer-blockers, insulators, promoters, retrogenes, 3D structures, and even non-DNA elements like non-protein-coding RNAs, histones, mitochondrial genomes, epigenetic influencers, etc., our gene-coding DNAs can create the variety we have. For popular consumption, future authors will have more classifications and different analogies, but the simple point is that genetic science is much more than about the genes themselves.

In a way, gene complexity is so high that human brains may find it impossible to fathom - in our languages of words - how they genuinely drive our construction through various manifestations. As a result, any book - however good - may appear to have an inadequate job in explaining the concepts undertaken. This book falls in that category, and it is not fault of the author. The book does what it sets out to do. Some readers may find the details insufficient, and some may find them overbearing. Most will need to come back to more work from the author to develop more understanding of the topic.

[Anton M · Rating 4 out of 5]

What makes us so special if we are not more different than yeast on your kitchen table?!
"The more sophisticated an organism, the higher the percentage of junk DNA it contains."

This book felt like a follow up from N. Carey’s book “The Epigenetic Revolution. But this time it was more detailed and tougher to understand as a layman. Nevertheless, this book can be red on its own and offers an understanding of the importance of the “junk dna” and further entangles or tangles the complexity of the genome and related problems, risks and opportunities.

While reading "Gene an intimate h..." I was amazed to learn that some genetic diseases like ALS are caused by single gene defect while schizophrenia caused gene polymorphisms. This book offers even a deeper dive into the detail grad for a layman. While schizophrenia is a result of multiple gene defects, they might be caused by multiple random variations and defects at the epigenetic level which have an impact on protein coding genes. This level of complexity is simply staggering. I highly regard scientist endeavouring on such exploration.

“although DNA is fantastic at storing information, it’s no use in terms of creating something from that information, not even another copy of itself.” Rna on the other hand was self-sustaining and self-selecting thus, most efficient pairs of RNA molecules persisted over the course of evolution. This is the reason for the assumptions that Rna is the origin of life.

Interesting quotes/facts:
1. “Boys are more likely to have symptoms of an X-linked genetic disorder than girls, because the boys can’t compensate”. The same thing is mentioned by S. Mukherjee “Male readers of that last paragraph should take notice: we barely made it.” Despite the design vulnerabilities it was kept or rather it persisted.

2. “They found that the telomere shortening associated with obesity was even more pronounced than for smoking, equating to nearly nine years of life.”

3. “This is a problem for humans because we like living longer than evolution deems strictly necessary.”

[Erik Surewaard · Rating 4 out of 5]

Like the other book that she has written (on epigenetics), this is not an easy read. Before reading this book, it is even better to have read the book she wrote on epigenetics. This since this book on junk DNA makes use of concepts that are explained very well in her epigenetics book.

Due to the relative complex subject matter in this book, I again read only one or two chapters a day. This since it allowed me to ‘digest’ the topic at hand.

Like her book on epigenetics, this book on junk DNA describes stuff that was a real eye opener to me. Considering the attention on gene editing techniques like e.g. (and specially) CRISPR, there is a lot of attention in the investing world on companies having to do with using genes in some kind of way This book on junk DNA, doesn’t discuss gene editing techniques, but most certainly discussed methods like smallRNA that can solve diseases. Several startup companies are focussing on this and as such this book fits very well in the current focus on companies focussing on gene therapies.

Apart from the relevance, this book is also an excellent read. The author really knows how to keep the attention of the reader by mixing theory with practical examples and applications. This book really deserves at least four stars.

[Laura · Rating 2 out of 5]

While I greatly appreciated the books ability to offer great day-to-day analogies for complex molecular biology problems, I think the author's fear of going in depth was too great and harmed the final product. For a scientist, this is a boring book, and it actually doesn't shine any light in the dark (the footnotes were also horrible to navigate in the e-book).
Biggest issue and why the book doesn't get 3 starts from me were scientific errors. Nessa Carey declared that regions of DNA coding for ribosomal and transfer RNA are junk. With all do respect, they are considered bona-fide genes! She narrowed the definition of a gene to include a stretch of DNA coding for a protein, which is not what scientists define a gene to be. What we say is that a gene codes for a gene product! It's just that we define that gene product as something that has a clear final form and final function.
In conclusion: slightly more accurate science and more courage to give the readers some details would have made the book a more enjoyable read. The analogies and metaphors for the lay audience were indeed impressive and the highlight of the book for me.

[Alexander Telfar · Rating 4 out of 5]

Really interesting, and at times quite funny. Long and short non-coding DNA, epigenetics, splicing ... fascinating! The complexity of our genetics is almost incomprehensible (genes regulated by promoters and inhibitors, regulated by many different types of long non-coding DNA, regulated by epigenetics, mediated by short non-coding DNA, ... ). It is a wonder we are alive.

Protein splicing reminds me of data compression. The cell has learned to store patterns/recipes to create proteins instead of coding for each individually.

The complex gene regulation (e.g. epigenetics) reminds me of neural networks, and how they can change weights (or connections/promoters/...) between nodes (or genes). This seems quite similar to a the NeuroEvolution of Augmenting Topologies (an awesome algorithm).

My only criticism is that I found the sections on disorders caused by genetic malfunctions lengthy and not as interesting.

[Peter Grant · Rating 3 out of 5]

As someone with a professional interest in DNA, this book started off with some fascinating accounts of what lurks in 'junk DNA' and my interest was really piqued. Unfortunately, it tended to then try to explain some hugely complex medical issues but without the ability to keep this reader in the loop and a frustrating tendency to try to explain things with lego and velcro. There were plenty of diagrams but, for me, they were either too simple or a bit misleading. Much of the book discussed the weird types of RNA that have been discovered - very interesting - but then had a tendency to call that RNA junk DNA which just confused me further. All in all a fascinating book which got harder to read the further you got into it; it started at 4 stars and ended at 2 stars; hence a 3 star review.

[Ami · Rating 3 out of 5]

Interesting, and - most importantly - does not present genetics as the be-all-end-all cure for disease, as do the vast majority of genetics writers.

[Nadav · Rating 5 out of 5]

This book is in some sense a sequel to Nessa Carey's "The Epigenetics Revolution". Although you don't need to remember much from the previous book to understand this one, I do recommend reading the first book first.

Most people assume that DNA is a straightforward instruction booklet for building a body out of amino acids - like an IKEA booklet for how to build a cabinet out of wood and screws. However, as Carey clarifies in her previous book and even more so in this one, this isn't quite the case. Consider that the human body contains different types of cells that need to be built differently and operate differently. Or consider that at different times during our development from an egg and a sperm to a grown adult, again, different things need to be built. If we return to the IKEA booklet analogy, the DNA isn't one booklet - it's really a big stack of many IKEA booklets for building different types of cabinets, desks, beds, and so on. But in addition to these booklets, surely we need to have additional booklets which explain which other booklets to use where and when: For example, you need another booklet to explain that in a kitchen you should build cabinets, but not a bed. Or in a bedroom you should build a baby bed and a few years later, replace it by a bigger bed - but you shouldn't build 20 beds and fill the entire room with them. Where are these instructions? These instructions are also coded in DNA, but are NOT the normal protein-coding genes that people usually think is the sole content of DNA.

Historically, people called these non-protein-coding genes "Junk DNA" because it looked like no proteins were created from these pieces, just surely they must be junk. But it turns out, a lot of this "junk" actually has function, and this book sets out to explain some of these mechanisms whereby various "junk" pieces of DNA actually control where, when, and how much, the other genes become active. Some of these mechanisms are actually nested in complicated way - e.g., one mechanism promotes the expression of 10 other pieces of DNA which each promotes the expression of a different protein. All of these makes DNA much more complicated - and much more interesting - than people usually think. It also makes evolution more interesting - as genes are not really independent as naive readers of Dawkins might assume. The book also gives many examples of genetic disease which are caused not by a mutation in a single gene, but by a mutation in one of the "junk DNA" mechanisms which controls the expression of other genes.

I gave this book 5 stars for its importance, and how it (together with the previous book) helped me get a much better understand of how DNA really determines how the human body (and other organisms') works. I found this book harder to read than "The Epigenetics Revolution", but decided not to deduct a star for that - I think the material covered in this book is simply more complex than the previous book. Another problem is that there is a lot not yet known in this area, so some of examples that Carey gives sound a bit vague because we really don't understand every detail yet.

[Arti · Rating 4 out of 5]

I had really enjoyed the first book by Nessa Carey on Epigenetics and was looking forward to continuing that journey further with Junk DNA. And this book has the same writing style, uses specific examples of genetic diseases to map different types of junk DNA and their varied functions, and is easy to read… and while I can say that I understood the high level concept - the complexity and the multilayered dynamics of the interplay between different elements of our genome - epigenetics, junk DNA, non proteins coding RNAs, small RNA, retrogenes, etc., I have to admit that I am finding it difficult to remember the specifics and the details.

But no doubt, it’s a fascinating subject that opens many questions, reminds us of how little we know of how life functions (despite all the progress we claim) and above all brings out the complexity, the specificity of the regulatory process and describes how this control flexibility explains the evolutionary complexity in humans who have the same number of genes (and often equivalent genes) with other organisms.

The book serves as an introduction on junk DNA - describes that it forms 98% of our genome and does not code for proteins but helps in their proper production of coordination, shows that it is is central to the control of gene expression and the many examples in the book show varying degrees of control - from fine tuning individual genes to switching off entire chromosomes… it is not just gene expression, but interestingly multiplicity of function, from forming specific structures in the chromosomes that prevents our DNA from unravelling and becoming damaged, to anchor points when chromosomes are shared equally between different daughter cells during cell division, to coding for RNA molecules that in turn help in protein production, and then some parts that are genetic interlopers, derived from the genomes of viruses and other microorganisms that have integrated into human chromosomes, like genetic sleeper agents.

The multilayered interlocking complexities are so high (not just interactions between between elements of the genome but also 3D structural play that allows seeming far pieces of code to come in proximity to influence by changing it conformations or shape)… it surprising that so little of it goes wrong and most of us function normally most of the time - it’s simply amazing!

It’s an emerging field and a lot is left to be learnt, but even early studies are helping diagnose and treat diseases and opening up new therapeutic pathways (such as RNA-based drugs that target the interaction of long non-coding RNAs with the epigenetic machinery). It is strange that the subject is filled with controversy - the fact that so many diseases can be traced back to variations in the junk region of the DNA should be enough for us to accept that junk DNA (at least a large part of it) has a function!

[Philemon - · Rating 5 out of 5]

98% of our DNA has until recently been considered "junk." That's the percentage that's not devoted to recipeing proteins, which for decades was supposed to be what DNA was all about. But the view of so-called junk DNA has been slowly changing. Better tools and procedures have allowed researchers to locate mutations implicated in rare genetic diseases, and many of these mutations turn out to be located in the "junk" areas. As clues mount, scientists can start connecting dots and developing theories regarding multitudes of previously unconsidered ways in which genetic errors can cause problems.

Ms. Carey's book does not make many generalizations about junk DNA's overall purposes might be. Instead she relates disparate tales of research results as relating to known genetic disorders. Her stories exemplify the strange, non-intuitive ways that genetic information can interact. It doesn't seem likely that science will soon have an orderly story to tell about how it all works.

Many of the interactions are actually epigenetic rather than genetic, meaning that they concern markers added to the the genetic code rather than the code itself. Epigenetic markings can be prompted by changes in the cell environment. Their purpose is to enable, amplify, damp down, or turn off individual genes. Their role and presence vastly complicates the whole genetic picture. Richard Dawkins's view of genes as simple, coherent actors seems increasingly naive.

This book is well and entertainingly written, but may be too technical for some readers. Something of a refresher course in cell biology might be advisable before giving this a go.

[Kawtar Bateman · Rating 4 out of 5]

Fascinating and funny at the same time.

Genetics has always been an interesting field, when we read about its junk part, it only gets more captivating. You learn new information, things you never thought could ever happen, making you question who you really are after all, and you start seeing your little tiny cells differently.

It is true that I'm familiar with many things mentioned. At times, it was like she was repeating the details over and over. Some explainations were quite "too simple". However, I liked the analogies she used to describe the different phenomena and diseases, her witty comments made the book more enjoyable too.

I've heard many good things about her other book (Epigenetics), since that is her first one, maybe I should have started with it?
Anyway, I look forward to reading it.



"While it might seem that evolution would have selected against this dangerous situation, we need to remember yet again that natural selection is about compromise, not perfection.The advantages of producing antibodies to fight off infections and thereby keep us alive long enough to reproduce clearly outweigh the potential disadvantages of an increased cancer risk."


"When we really think about the complexity of our genomes, it isn't surprising that we can’t understand everything yet. The astonishing triumph is that we understand any of it. There is always something new to be learnt, out there in the dark."

[Amo Rise]

Kısaca: Genomumuzun büyük çoğunluğu, protein üreten anlamlı bir koddan oluşmuyor. Carey ise bu kitapta; o büyük kısmın işe yaradığı hipotezini teknik terimlerle (ve bence bunaltıcı konularla) anlatmış.

Benim değinmek istediğim konu ise Carey'in en sevdiği, Epigenetik.

Epigenetik, bilimsel yöntemlerle açıklanan genç bir alan. Benimse kafamı karıştıran, daha öğrenme sürecindeyken bile şüpheyle yaklaştığım bir hipotez.

Darwinci evrime karşı daha “Lamarckvâri evrimi”, kendiliğinden olana karşı daha “bilinçli olanı”, binlerce nesle karşı “bir nesilde değişimi" (hatta bazı kesimlerce materyalizme karşı yaratılışçılığı ve "insanın özel oluşunu") vurgulayan bir kalıtım açıklaması.

Şayet bir canlı, yaşarken etkilendiği özellikleri yavrusuna öylece geçirebilecekse; hele ki bu özellikler sosyal durumlarsa; o vakit sürekli bahsedilen -ve kanıt olarak gösterilen- deneylerin tekrarlanması gerektiğini düşünüyorum, zira kanıtlar ciddi ve açık olmalı. Sonuçta bir anne farenin kiraz çiçeği kokusundan korkmayı öğrenmesi bireysel bir şeydir ve bunu yavruya biyolojik olarak aktarması kulağa çok zorlama geliyor.

Ek olarak, bu konuyu araştıranlar, bazı genetik olayların “epigenetik” olarak yanlış yorumlanma ihtimalinden de bahsediyorlar. Eğer yaşadığınız bir olay, stres gibi psikolojik veya daha fiziksel bir etkiye sahipse, bu sizin genetiğinize etki edebilir.

Yanlış düşünüyor da olabilirim tabii; yine de bu hipotezlerin evrim (ve biyoloji) konusunda genelgeçer hâle geldiğini görmeyi bekleyeceğim.

[Uyar · Rating 4 out of 5]

Zor gerçekten çok zor bir kitap.. genetik jargonuna aşina iseniz biraz daha kolaylaşa bilir. Junk kelimesi çöp olarak Değerlendirilip protein Kodlamayan (non-coding) DNAmızın %98lik bölgesi araştırıldıkca çöp olmadığı açıkça görülmekte... yazar Okuma akışını korkunç derecede bozduğunu düşünerek metin içinde spesifik gen isimleri kullanmamaya özen göstermiş olması bir yandan iyi görünürken diğer yandan sürekli dip notlara gitmeyi gerektirmekte... Biraz meraklı bir okuyucu iseniz de sürekli Pubmed`e gitmekten de yorulabilirsiniz... Yine de bu kadar karmaşık bir konu olan epigenetik Anca bu kadar güzel anlatılabilir. Yazar Carey yanında Çevirmen E Yılmaz’a da teşekkür etmemiz gerekir.
Karmaşık biyolojik yaşamın oluşmasında protein dizileri yanında protein Kodlamayan RNAlar Telomerler hızlandırıcılar promotorlar epigenetik uçbirleştirme yalıtkanlar centromerler retromerler vs Hepsi Ve daha fazlası etkili ve bizler temel olarak bu etkileşimlerin ürünleriyiz...
“ Bilim insanları olarak bizler eğitimleri ve kariyerleri boyunca pek çok konu hakkında düşünmek için eğitilmiş izdir ancak nadiren kafa yormamızı istedikleri nokta Şansın oynadığı roldür. Bunu yaptığımızda bile genellikle çalışmalarımızı rastgele dalgalanmalar (random fluctuations) veya rastlantısal değişim (stochastic variations) gibi terimlerle süsleriz aslında bu utanç verici çünkü bazen şans (luck) muhtemelen daha iyi bir açıklamadır”