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The language of genes has become common parlance. We know they make our eyes blue, our hair curly, and they control our risks of cancer, heart disease, alcoholism, and Alzheimer's. One thousand dollars will buy you your own genome readout, neatly stored on a USB stick. And advances in genetic medicine hold huge promise.
We've all heard of genes, but how do they actually work? There are six feet of DNA inside every one of your cells; this encodes 20,000 or so genes, tangled into a mass of molecular spaghetti. This is the text of the cookbook of life, and hidden within these strands are the instructions that tell cells when and where to turn genes on or off.
In 1935, Ernest Hemingway was supposedly given Snow White, a six-toed cat who went on to father a line of similar offspring that still roam the writer's Florida estate. Scientists now know that the fault driving this profusion of digits lies in a tiny genetic control switch, miles away (in molecular terms) from the gene that "makes" toes. Researchers are discovering more about the myriad molecular switches that make sure genes are turned on at the right time and in the right place, and what happens when they don't work properly. This is allowing a four-dimensional picture of DNA to be built--a dynamic biological library, rather than static strings of code. Geneticist Kat Arney explores the intricacies of how, out of this seeming genetic chaos, life is created.
Setting the scene, outlining my curiosity about how our genes work, current questions and challenges in the field, and some of the characters (both people and genes) that we'll meet.
2. It's not what you've got, it's what you do with it that counts
Explaining exactly what we mean by a gene, and what we know about the contents of our genome (the sum total of all our DNA), and genomes of other organisms. We explore the results from the new ENCODE project (and the controversy it generated), and what we know about the contents of the human genome, as well as the genomes of other organisms.
3. Throwing the switch
We discover the stories behind the early discoveries on how genes are controlled back in the 1960s, including Nobel prize-winners Jacques Monod and Francois Jacob, whose work on bacteria forged the field of molecular biology, and Mark Ptashne, the violin-playing scientist who first figured out the genetic 'switch' that turns on genes in simple viruses. We then move forward through the decades to today, building up an increasingly complex picture of the carefully choreographed molecular ballet that results in a gene being switched on.
4. Cat toes and fish hips
We take a look at little stretches of DNA called enhancers, which act as genetic 'switches' that tell a particular gene to be turned on in a particular place and time. Faults in these regions are responsible for six-toed Hemingway cats, human werewolf syndrome, whether stickleback fish have a pelvis or not, skin colour, and much more. We look at how some of these rarities have been the playground for evolution, generating new and wonderful species along the way.
5. Did you take your mice to the moon?
So we have our genes, and we have our switches – but how does it all work together? This chapter explores how nature interprets the instructions in the genome to create life, and the influence of the environment on gene activity. We also discover that biology is much more 'wobbly' than might be expected, and why we don't look like chimps despite being made of pretty much all the same stuff.
6. A brief encounter with a dog on a leash
We're used to seeing images of DNA as a static, twisted ladder, or perhaps neatly-aligned X-shaped chromosomes. But the reality is very different. We have more than two metres of DNA packed into each one of our cells, and managing this mass of biological spaghetti is a major challenge. This chapter looks at DNA as a dynamic, 3-D molecule, exploring new scientific ideas about how it's packed, unpacked, repacked and organised.
7. Pimp my genome
On top of the genetic on and off switches that are scattered through our genome, hard-coded into our DNA, there are further layers of control on top - something known as 'epigenetics'. A multitude of molecules act together to orchestrate gene activity, and finding out how they work – and whether they can be manipulated by our lifestyle, environment or medication – is a hot topic in science.
8. Ever increasing circles
We learn about some of the quirks and curiosities in the way that our genes are 'read', from nature's 'red pen', peppering our genetic messages with corrections and edits to cells full of mysterious circles.
9. We're all going to the zoo
We take a trip to the 'RNA zoo' – a menagerie full of strange creatures that have recently been found to exert a powerful influence on gene activity. Some of these are now being used to 'hack' the genome, switching genes on and off at will to reveal new insights and even potential future treatments for human disease.
10. They **** you up, your mum and dad
One of the most fascinating phenomena in genetics is imprinting – the fact that certain genes can 'remember' whether they came to you from mum or dad. This chapter looks at how these memories are imprinted in our genome, and how they are wiped from one generation to the next. We also meet some curious mice with Mickey mouse gloves which shouldn't exist, and discover how they share an unexpected link with one of Charles Darwin's supposedly wrong ideas.
11. Night of the Living Dead
Our genome is packed with the remnants of long-dead genes, along with plenty of ancient defunct viruses. But, just like in the movies, these zombie genes can rise again to wreak havoc – or, less dramatically, be put to good use by cells.
12. In search of the 21st century gene
Bringing everything together to sum up what we do – and don't – know about what genes are and how they work. We pose some unanswered questions and controversies, as well as exciting directions for future research and applications in medicine and other fields.