The Deeper Genome: Why there is more to the human

genome than meets the eye

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 OUP CORRECTED PROOF – FINAL, 27/3/2015, SPi

the
deeper
genome
Why there
is more to the
human genome
than meets
the eye

JOHN PARRINGTON

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3
Great Clarendon Street, Oxford, OX2 6DP,
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# John Parrington 2015
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ACKNOWLEDGEMENTS

I would like to thank a number of people who have helped bring this book to
fruition. I owe particular thanks to Latha Menon, my editor at Oxford University
Press, who was both firm in her suggestions about where the text needed
modifying, and encouraging where she felt it did not. I would also like to thank
Emma Ma and Jenny Nugee of the OUP editorial team, for their help on a
multitude of practical matters, and Elizabeth Stone at Bourchier Limited for her
meticulous copy-editing of the book. I gained some very valuable insights and
suggestions for modifications to the text from a number of people who read my
original proposal and various drafts of the book, namely Guida Ruas and Martin
Empson, together with four anonymous reviewers. I also owe many thanks to
Anthony Morgan for producing the photo for the book cover. For their excellent
assistance with marketing and publicity I would like to thank Phil Henderson and
Kate Farquhar-Thomson of OUP, as well as Jonathan Wood of the Oxford
University Press Office. I would also like to thank Kate Gilks of OUP and Andrew
Hawkey for their skill and expertise in proof-reading and compiling the index. I
am very grateful to friends and colleagues who have indulged my many queries
and speculations about matters relating to the genome during the writing of this
book, as well as providing very helpful feedback and suggestions. Finally, I owe
special thanks to my family, who have provided me with love throughout the
writing and production of this book, and put up with the many hours spent
researching and writing when it cut into our time spent together as a family.

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CONTENTS

Introduction: How the Genome Lost Its Junk 1

1. The Inheritors 12

2. Life as a Code 25

3. Switches and Signals 42

4. The Spacious Genome 58

5. RNA Out of the Shadows 74

6. It’s a Jungle in There! 87

7. The Genome in 3D 99

8. The Jumping Genes 112

9. The Marks of Lamarck 126

10. Code, Non-Code, Garbage, and Junk 140

11. Genes and Disease 152

12. What Makes Us Human? 166

13. The Genome That Became Conscious 181

Conclusion: The Case for Complexity 195

Glossary 208
Endnotes 210
Index of names 237
Index of subjects 240
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INTRODUCTION

How the Genome Lost Its Junk

‘Sit down before fact as a little child, be prepared to give up every precon-
ceived notion, follow humbly wherever and to whatever abysses nature leads,
or you shall learn nothing.’ Thomas Huxley
‘What is a scientist after all? It is a curious person looking through a keyhole,
the keyhole of nature, trying to know what's going on.’ Jacques Cousteau

It was on the morning of 5 September 2012 that I first heard about the death of
‘junk’ DNA. I was sitting at a desk at The Times newspaper in London; to one side,
through huge windows, I could see the Thames, Tower Bridge—which all sum-
mer had been sporting the Olympic and Paralympic symbols—and beyond that
the Shard, the London Eye, and other famous landmarks. Above me, in the open-
plan building occupied by Rupert Murdoch’s News International company, was
the floor occupied by the Sun, with its huge, framed past front pages with head-
lines like ‘Up Yours Delors!’ and ‘Sling Your Hook!’, references to European
Commission President Jacques Delors and radical Muslim cleric Abu Hamza,
respectively. At the time the Sun was embroiled in a major investigation into its
alleged use of illegal phone tapping.1 Although it was 9.30 a.m. the offices were still
largely empty; the deceptive lack of activity was contradicted, however, by the influx
of messages in my e-mail inbox from other journalists, pitching ideas to the editors
for the day’s stories even as they travelled to work by the Underground or rail.
Although I’d been working at The Times for over a month, my position funded
by a British Science Association Media Fellowship,2 I still felt a bit of an imposter,
perhaps because the day-to-day activities of being a journalist were so different

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THE DEEPER GENOME

compared to my normal role as a biologist and lecturer at Oxford University. One

particular difference was the tempo; while in my regular job I may spend months,
even years, gathering data for a study and presenting it for publication, submitting
the manuscript to a journal, and then spending more time battling with anonym-
ous reviewers who can either damn the whole study with a dismissive word or
demand further data, here the pace of publication was very different.
So a typical day at The Times began by scouring Eureka Alert and other websites
that gather together the latest press releases, funding announcements, and other
news from the world of science.3 This would form the basis of my day’s pitch to
the news editors, which typically would consist of two, maybe three, stories I
thought might compete with other news from the world of politics, economics,
sport, and scandal. After anxiously waiting while the editors had their mid-
morning meeting, I would hopefully get the go-ahead to write 600 words on
one topic, 400 on another, all to be submitted to the news desk by 3 or 4 p.m. to
have any chance of making the printed paper. Around me, kick-started into life by
similar demands, the office was now a whirring hub of activity as everything
became subsumed towards a central goal—the production of the next day’s news.
If I had written well, and, as important, proved lucky against competing news
items, I might see one or two of my articles online by early evening. However, the
real test of how well I was doing would be seeing a piece that I’d written appear in
next day’s print edition. And then, like rubbing clean a slate, the next day kicked
off exactly the same way.
This morning, however, it was clear something odd was afoot. Over a dozen
different press releases had appeared on Eureka Alert, all from different research
institutions, but all mentioning ENCODE—an acronym for ENCyclopedia of
DNA Elements. As I read further, I learnt the reason for this sudden burst of
information: ENCODE was the culmination of almost a decade’s research involv-
ing 442 scientists from 32 institutions and costing $288 million.4 And its claims
seemed as big as its budget. So while the original Human Genome Project
provided the sequence of letters that make up the DNA code, ENCODE appeared
to have gone substantially further and told us what all these different letters
actually do. Perhaps most exciting was its claim to have solved one of the biggest
conundrums in biology: this is the fact that our genes, which supposedly define us
as a species, but also distinguish you or I or anyone else on the planet from each
other, make up only 2 per cent of our DNA. The other 98 per cent had been

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HOW THE GENOME LOST ITS JUNK

written off as ‘junk’; however, this raised the question of why our cells should
spend vital energy replicating and storing something with no function. The
existence of so much junk DNA had also featured heavily in debates between
evolutionists and creationists, for why would any creator design a genome in
which only 2 per cent actually works?
Now, as I read though, I found that ENCODE’s new findings, all synchronized to
appear simultaneously in 30 linked publications, had a new and excitingly differ-
ent take on this matter. By scanning through the whole genome rather than just
the genes, and using multiple, cutting-edge approaches to measure biochemical
activity, ENCODE had come to the startling conclusion that, far from being junk,
as much as 80 per cent of these disregarded parts of the genome had an important
function. Indeed, for Ewan Birney of the European Molecular Biology Laboratory
near Cambridge, the charismatic spokesperson of the project, this was probably
an underestimate, since it was ‘likely that 80 percent will go to 100 percent. We
don’t really have any large chunks of redundant DNA.’5 The path-breaking nature
of the project was emphasized by another ENCODE researcher, John Stamatoyan-
nopoulos of Washington University in Seattle, who predicted that the findings
would ‘change the way a lot of concepts are written about and presented in
textbooks’.6 Perhaps most excitingly for a general audience, ENCODE also claimed
that its findings were casting important new light on links between the genome
and common diseases such as heart disease, diabetes, auto-immune conditions,
and mental disorders like schizophrenia.6
Clearly, this seemed like big science at its best, and, as such, I co-wrote a story
with Tom Whipple for The Times, in which we spelled out the study’s implications.
It appeared in the following day’s paper entitled ‘Rummage through “junk” DNA
finds vital material’.7 Similar positive assessments of the new findings appeared in
media outlets across the world, all of which repeated the project’s main conclu-
sion that the idea of ‘junk’ DNA had been overturned by the discovery that as
much as 80 per cent of the genome had an important function.8,9,10 This was also
the message from serious science journals such as Nature and Science, with the
latter headlining the discovery ‘ENCODE project writes eulogy for junk DNA’.11
By the end of my six-week placement at The Times, I’d published a total of
twenty-two stories and features, on topics ranging from why chocolate is addict-
ive, the discovery of the oldest tooth filling in history, and whether becoming a
eunuch would make men live longer, to the burning question of whether a

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THE DEEPER GENOME

potential super-volcano is lurking under the city of Naples.12 But the story that
most resonated for me on a personal level was the ENCODE findings. I resolved to
find out more about their implications, not just for my own research, but also
with regard to the much bigger question of how our genomes define us both as a
species and as individuals. Most intriguing was the controversy that erupted a little
while after the ENCODE findings were published. So an article published in the
journal Genome Biology and Evolution in February 2013, attacked the findings in a
vitriolic tone not normally associated with scientific debate, or at least not in the
pages of an academic journal.13 According to the article, the claims of ENCODE
were ‘absurd’, its statistics ‘horrible’, and it was ‘the work of people who know
nothing about evolutionary biology’. And in a subsequent interview, lead author,
Dan Graur of Houston University, said ‘this is not the work of scientists. This is the
work of a group of badly trained technicians.’14 A central criticism was that
ENCODE researchers had confused activity with functionality. ‘Just because a
piece of DNA has biological activity does not mean it has an important function
in a cell,’ said Graur. ‘Most of the human genome is devoid of function and these
people are wrong to say otherwise.’14
In contrast, there was the view of John Mattick of the Garvan Institute of
Medical Research in Sydney, who argued that the ENCODE leaders were, if
anything, too conservative in their claims, and that the findings showed ‘we
have misunderstood the nature of genetic programming for the past 50 years’.15
Another proponent of this view, Evelyn Fox Keller of the Massachusetts Institute
of Technology, believes recent ‘genomic science has changed the very meaning of
the term, turning the genome into an entity far richer, more complex, and more
powerful—simultaneously both more and less—than the pre-genomic genome,
in ways that require us to rework our understanding of the relation between
genes, genomes and genetics’.16
So who is right? I resolved to find out, and this book is partly a result of that
quest. However, while my interest in writing this book began with ENCODE, it has
subsequently grown to encompass a much wider field of enquiry, all relating to
the topic—how do our genomes make us human? This is a question that often
comes up in the lectures and tutorials I give to medical and biology students at
Oxford University in which we discuss the genetics of disease; for instance, why
are some people more susceptible to certain disorders than others? But it also
flows from a long-standing personal interest in what distinguishes humans as a

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species, but also as individuals. Unfortunately, for some time now I’ve been
dissatisfied with the available explanations as to how our human genomes
work, on the one hand to distinguish us from other species on the planet, and
on the other to create the unique mix of personality, capabilities, needs, desires,
and susceptibility to illnesses and disorders, that define us as individuals.
As a child, I remember being fascinated by my parents’ copy of The Naked Ape,
by Desmond Morris. This book became a publishing sensation in the 1970s with
its claim that modern human behaviour and society was largely rooted in instincts
that had evolved in the Stone Age.17 There was a problem though, in that Morris’s
take on prehistoric life was about as accurate as the 1950s cartoon The Flintstones,
or the ’60s film One Million Years BC starring Raquel Welch. However, what The
Naked Ape lacked in authenticity was more than compensated by its numerous
references to sex, which, to someone just reaching puberty, were almost as
alluring as Welch’s animal skin bikini. For a teenage boy just starting to worry
about my attractiveness to the opposite sex, being told that humans not only have
the largest brain compared to body size, but also the largest penis, making them
the ‘sexiest primate alive’,18 was sweet music to my fragile ego. Meanwhile,
learning that humans’ fleshy ear lobes, unique to our species, are erogenous
zones, or that women’s breasts are an important sexual signalling device rather
than simply providing milk for babies,19 was definitely something for my newly
hormone-stimulated brain to chew over. And finally, Morris’s claim that monog-
amy evolved so that men out hunting could trust their mates were not having sex
with other men, and that human ‘nakedness’ helped intensify pair-bonding by
increasing sensory pleasures,19 were all food for thought to a teenage mind.
Unfortunately, as scientific fact such claims were about as substantial as Welch’s
bikini, although they could possibly be excused by a lack of understanding of
human evolution and its molecular and cellular basis at this time. Yet what is
surprising is how little many ‘biological’ explanations of human behaviour and
society have changed since the 1970s. Take, for example, a recent book about
human culture by Mark Pagel of Reading University, which moves in a few pages
from self-sacrifice in amoeboid slime moulds to what Pagel calls a ‘helping gene’
that codes ‘for an emotion that disposes people to be friendly’.20 This sounds quite
nice except this helping gene’s influence only extends to people of the same
nation; towards other national groups it becomes the ‘jingoism’ or ‘xenophobia’
gene. The author ends by saying ‘next time you feel that warm nationalistic pride

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at the sound of your national anthem or the news of one of your country’s
soldiers’ valour, think of the amoebae!’21
One problem with this argument is its assumption that all members of a nation
state behave in a similarly patriotic manner. So it fails to explain why millions of
people in Britain opposed their government and marched against the recent wars
in Iraq and Afghanistan.22 But a more fundamental difficulty is that the proposed
‘gene’, which somehow manages to combine both nice and nasty characteristics, is
a complete figment of the author’s imagination. And, lest this be seen as an
isolated incident, I could point to a range of other examples in which single
genes are said to determine intelligence, personality, and even men’s supposed
unwillingness to do the ironing, without scientific evidence to back up such
claims. In fact, for all the lip service paid to genetics in such accounts, the ‘gene’
here might as well be made of green cheese given the lack of any real attempt to
engage with actual molecular mechanisms rooted in the real genome.
Actually, this is not quite true. The claim that homosexuality is due to a ‘gay’
gene, which made headlines across the world in 2003, was based on a study
published in the prestigious journal Science. Evidence was presented that gay men
had specific differences in a region on the X chromosome, Xq28, that was claimed
to be linked to their homosexuality, and passed down through the mother.23
What followed was a huge debate about the implications of the discovery. In the
gay community itself reactions ranged from fears that screening programmes
might identify and abort ‘gay foetuses’ on the basis of their possession of the gene,
to those who thought the discovery would scientifically ‘legitimize’ homosexual-
ity and therefore help end gay oppression, although this ignores the fact that the
clear biological basis of skin colour has not prevented oppression based on this
difference.24 Such was the publicity around the discovery that a T-shirt with the
slogan ‘Xq28—thanks for the genes, Mom!’ became a popular item in many gay
bookstores. Missing from much of the coverage, however, was that what had been
discovered was not an actual gene but merely an association with a DNA region
on the X chromosome. And two decades later, the authors have failed to identify
such a gene, while attempts to reproduce the findings by others have been equally
negative, leading to suspicions that the original ‘discovery’ was just a statistical
artefact.25
Such failed attempts aside, one undoubted reason for the popularity of
accounts of human behaviour and society that make no attempt to engage with

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actual molecular mechanisms, is that they tell entertaining ‘just-so’ stories about
human evolution without having to bear scrutiny as to whether such stories are
actually true. In this sense, as science journalist Tim Radford has noted, the ‘gene’
here is not so much a real object as a ‘metaphor, an analogy, an “as if”, a useful way
of thinking about how behaviours, strategies and responses might have
emerged’.26 Now while I’m all for metaphors as a way of making complicated
scientific concepts comprehensible, a problem arises when these get in the way of
a true understanding of the material basis of nature. Taking an example from the
physical sciences, the initial model of the atom proposed by Ernest Rutherford in
1911 pictured it as a miniature solar system, with electrons orbiting the nucleus
just as our own planet orbits the Sun; however, subsequent studies showed that
this metaphor was far too simplistic. Surprisingly, in the biological sciences far
too many popular accounts are still anchored in an old-fashioned view of genes
that either sees them as abstract units with no material form, or if they do
acknowledge this link, subscribe to the crude picture of genes as ‘beads on a
string’, discrete and isolated entities on each chromosome.
In contrast, while in this book there will be plenty of speculation about the link
between genes and what it means to be human, my aim will be to make sure this is
always backed up with evidence of real molecular mechanisms based on the most
cutting-edge studies of the genome. Here, though, we face a problem. While key
individuals involved in the Human Genome Project, such as Sir John Sulston of
the Sanger Institute near Cambridge, promised that, ‘for the first time we are going
to hold in our hands the set of instructions to make a human being’,27 and British
Science Minister Lord Sainsbury said ‘we now have the possibility of achieving all
we ever hoped for from medicine’,27 the reality has been rather different. So when
scientists sought to use the genome to identify links between differences in the
DNA code and common disorders like heart disease, diabetes, and mental condi-
tions like schizophrenia, bipolar disorder, and autism, the problem was not
finding genetic links to these disorders but rather the astounding number of
these.28,29 Instead of identifying just a few strong genetic links with each condi-
tion, as had been commonly predicted, scores or even hundreds of such links have
been made, with each only apparently contributing a tiny amount to the chance of
succumbing to these disorders. Such findings seem to mock the idea that we can
find meaningful, and useful, links between our genomes and such conditions, and
if true for disease, surely it must be more so for other aspects of being human,

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such as our unique personalities and capabilities. This has led one critic of the
genome project—neuroscientist Steven Rose of the Open University—to argue
that ‘they said this was the greatest achievement since landing a man on the moon.
One even said it ranked with the discovery of the wheel. And yet none of this
cornucopia of benefits has come out of it.’30 Another critic, bioethicist Tom
Shakespeare of Newcastle University, has said ‘we share 51 percent of our genes
with yeast and 98 percent with chimpanzees—it is not genetics that makes us
human’.27
In this book, my aim is to find a middle way between the view that the
complexities of the human condition can be reduced to simple, hypothetical
‘genes’ without any mechanistic underpinning, and the opposite view that sees
things as far more complex, yet rejects the idea that we have learned anything
useful from the genome project, about both the diseases that afflict us as a species,
and what it means to be human. In so doing, I will be drawing on many years of
experience studying genes and how they function. In my quest to understand how
cellular signals regulate important bodily processes, I have isolated and charac-
terized novel genes and studied their functional properties in a test tube and in
cultured cells, but also what happens when their activity is inhibited or altered in a
living animal. This has allowed me to appreciate the power, but also limitations, of
the so-called ‘reductionist’ approach to biology.
Such an approach aims to understand complex biological systems by dissecting
them into their constituent parts, or as Francis Crick, co-discover of the DNA
double helix put it, ‘to explain all biology in terms of physics and chemistry’.31 The
power of this approach was demonstrated to me when my colleagues and I used it
to show that a single gene codes for a protein in the sperm which triggers the
chemical signal in the egg that stimulates embryo development.32,33 However,
while studying the role of genes in the living organism, I have also increasingly
come to realize the complexity of their behaviour. A common method for
studying how genes work and their function within the body is to breed animals
in which the action of a particular gene is inhibited by genetic engineering, thus
creating a ‘knockout’ mouse.34 Such animals have become very important
‘models’ of human disease. Yet, surprisingly, in many cases abolishing a gene’s
activity has little effect on the whole organism, or leads to opposite or very
different effects than predicted based on its properties in a test tube or in cells
in a culture dish. Such unexpected findings are often said to be due to

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‘compensation’ by other genes during embryo development but this is really just a
hand-waving gesture to convey the fact we often know very little about why
particular genomic manipulations have unforeseen effects.31 What these findings
do suggest is that while isolating the effects of one gene from others in the body
can lead to important insights, ultimately, gene action can only be properly
understood as part of a wider whole. And if true for a mouse how much more
so for humans, with our complex behaviour and culture driven by social innov-
ation as much as by biology.
So does this mean that attempts to find genetic links to the complexities of
human behaviour and society are doomed to failure? In this book I intend to show
this is far from the case, but I also want to challenge some long-held assumptions
in biology: one being the idea that genes can be treated in isolation, and also the
very definition of what we mean by a gene. To do this I will not only explore what
the ENCODE findings have to tell us about this question, but also investigate what
I believe is a more general shift taking place in our perception of the genome and
how it works. Importantly, this shift is based on new technologies that mean that,
rather than studying single genes in isolation as previously, we can now observe
changes in the activity of the genome as a whole.35 This analysis can extend both
to a whole organ like the human brain, but also allows us to study how genes are
switched on and off, in real time, in a living cell, something undreamed of only a
few years ago.36
Based on the findings emerging from the use of such technologies, I will look at
important new developments like the increasing recognition that, far from simply
being a linear code, the genome only really makes sense as a 3D entity.37
Moreover, this 3D entity dynamically changes in response to signals originating
both from within, and outside, the cell. Another important development is the
recognition that RNA, DNA’s chemical cousin, plays a far more important role in
the cell and organism than previously thought.38 So instead of simply being a
messenger between DNA and proteins—the building blocks of the body—RNA is
proving to have a multitude of other key roles, and on a much vaster scale than
could have been imagined. Finally, new evidence is emerging that, far from being a
fixed DNA ‘blueprint’, the genome proper is a complex entity that includes
proteins, and both the DNA and these proteins can be chemically modified in a
far more rapid, and reversible, fashion than suspected.39 This makes the genome
exquisitely sensitive to signals from the environment, and challenges the idea that

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life is merely a one-way flow of information from DNA to organism. Perhaps

most surprisingly, the genome’s status as a structurally stable unit is being called
into question, with evidence that certain genomic elements have an ability to
move about, sometimes to the detriment of normal cellular function, but also
acting as a new source of genome function.40,41,42
Excitingly, while the significance of such phenomena for long-term evolution-
ary change remains controversial, there is increasing evidence that these newly
recognized features of the genome may have played a fundamental role in the
emergence of Homo sapiens as a unique species with self-conscious awareness and
the power to transform its environment in a way that sets it apart from all other
life forms on the planet.43 This focus on human beings will be an important theme
of this book, for although I will show how studies on organisms ranging from the
humble bacterium to our closest living animal cousins, chimpanzees, have trans-
formed our understanding of human biology, ultimately it is with our own species
that I will be most concerned. And I will be aided in this task by the fact we can
now study the genomes not just of living primates, but also extinct proto-human
species like Neanderthals.44,45 In addition, it is becoming increasingly feasible to
determine the complete DNA sequence of genomes, as well as chemical modifi-
cations of this DNA and its associated proteins, from large numbers of living
human beings.46
Before tackling these important new reconsiderations about the genome
though, I first want to take us back in time to look at how scientists came to
understand how living things appeared on Earth, what led to the diversity of life
we see around us, and how genes and genomes mediate this process. In so doing
we will reach back into the lives and times of famous scientists like Darwin and
Mendel, but also lesser known figures whose theories and findings have never-
theless enriched our view of the cell and organism. Having thus developed a
secure foundation based on what, until recently, constituted the ‘orthodoxy’ in
this area of science, we will examine how this orthodox view is currently being
challenged. Using such new information we will seek to understand what this can
tell us about abnormalities of the human condition, not just ‘single-gene’ dis-
orders, but also more common disturbances, such as heart disease and diabetes,
and also mental conditions like schizophrenia and bipolar disorder, that afflict
millions of people across the world. In particular, we will investigate whether the
genetic complexity that appears to underlie these disorders mean that attempts to

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identify new methods of diagnosis and treatment are fatally flawed, or if there is a
path to a new understanding of these conditions despite this complexity. Finally,
we will explore how such new understanding of the genome is being used to
address a key remaining question for humanity, namely what is so special about
our own species that led us to such a primary position on Earth. With all that in
mind, it’s time to begin our quest. But first, a personal question—do you feel
lucky?

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THE INHERITORS

‘Every individual alive today, even the very highest, is to be derived in an

unbroken line from the first and lowest forms.’ August Weismann
‘If we didn’t have genetic mutations, we wouldn’t have us. You need error to
open the door to the adjacent possible.’ Steven Johnson

Do you ever feel you could use a little extra luck? Most of us can remember missed
opportunities when a helping hand from chance wouldn’t have gone amiss. Of
course, winners in life are often said to make their own luck, but the popularity of
lotteries across the world is proof of the hope that great fortune might nevertheless
turn up out of the blue with minimal effort. Unfortunately, at odds of 14 million to
one, you’re four times more likely to be killed by a lightning strike, and seven times
more likely to die falling out of bed than become a lottery multi-millionaire.47 But
what if I told you that you’re already a winner at odds that, in comparison to a
lottery win, would make the latter seem as certain as the sun rising each morn-
ing?48 To calculate just how lucky you are, first consider the chance that accom-
panied your mother and father meeting and deciding to have a child, estimated at
one in 20,000. Then there’s the good fortune that, of the four trillion sperm a man
generates in his lifetime, and the 100,000 eggs a woman produces, the pair that
gave rise to you happened to come together. But really we’re only getting started
when we consider the unlikeliness of your existence. For we must also consider an
even more implausible chain of events, namely that each of your ancestors lived to
reproductive age throughout the 3.7 billion years since life began on Earth. As
such, the unlikeliness of your birth comes to about 1 in 102,685,000, or putting it
another way, it’s as unlikely as the people in central London getting together, each
with a trillion-sided dice, and all rolling the same number.

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All of which means you are extraordinarily lucky to be here. But before you get
too carried away, you should also know you share similar good fortune with all
the other living things on Earth. That’s not just the other seven billion human
beings, but also the nine million other species on our planet. I’m not even going to
try and calculate the total number of organisms on Earth, but the fact that in your
guts alone there are 100 trillion bacteria, should give a sense of the scale we’re
talking about. And yet, like you, each individual organism on the planet came into
being through an extraordinarily lucky set of events. Yet there’s something even
more fundamental than good fortune that you share with all these organisms, and
that’s a common ancestry. From the mighty elephant to the minuscule flu virus, all
of life is, in a sense, our cousins.
This view of life—that undirected blind chance led to each individual organism
being alive today on Earth, and also that we share a common ancestry—was
famously proposed by Charles Darwin in The Origin of Species in 1859.49 Following
his trip around the world on the HMS Beagle, and stimulated by the diverse life
forms he had seen on the trip, Darwin concluded that there was no necessary
requirement for a supernatural creator to have produced the multitude of species
on our planet—instead this could be explained by a driving force he termed
‘natural selection’. This required both that populations of species varied in their
size, shape, and capabilities, and new environmental pressures acted upon these
variants to ensure ‘survival of the fittest’. Although this phrase conjures up the
image of nature as ‘red in tooth and claw’, Darwin was careful to point out that
although ‘two canine animals, in a time of dearth, may be truly said to struggle
with each other which shall get food and live’, the fight to survive is equally valid
for ‘a plant on the edge of a desert [struggling] for life against the drought’.50
Another important aspect of the theory is that for such survival to have any
consequence for future generations, survivors must pass on their attributes to
their offspring, who then represent a more significant proportion of the popula-
tion. To see how natural selection works, consider giraffes: while their ancestors
had shorter necks, a few animals with slightly longer necks would have had a
survival advantage in being able to access the highest leaves on the trees. Through
selection over generations, these variants came to predominate. Eventually, such
differences can lead to the birth of a new species.
In fact, Darwin was not the only person who had this crucial insight—so did
Alfred Russel Wallace. Unlike the wealthy, university-educated Darwin, Wallace

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THE DEEPER GENOME

began working for a living at 13 years old, first as a builder’s apprentice, later by
collecting biological specimens and selling them to collectors. Wallace was also a
socialist who continued promoting his radical views until his death at the ripe old
age of 90.51 However, despite these differences, Wallace reached the same con-
clusions about the evolutionary process as Darwin through a remarkably similar
route. Importantly, he had the same crucial exposure to an extraordinary number
of species and their variants during his travels around South America and what is
now Indonesia, as Darwin had on the HMS Beagle. Moreover, Wallace arrived at
the idea of a struggle for existence being the driving force for evolution after
reading Thomas Malthus’s An Essay on the Principle of Population, exactly as Darwin
had years earlier. In 1798 Malthus proposed that famine and disease were an
inevitable feature of human society, since, while food supply only increased
linearly, populations grew in an explosive, exponential fashion. In particular, he
believed that the ‘lower orders’ were primarily to blame in the latter respect, being
too inclined to have children.52 Many critics, then and subsequently, have pointed
to flaws in Malthus’s reasoning, such as the fact he ignored the likelihood of
technological advances in food production.52 An additional flaw was his disregard
for the possibility of birth control, which, ironically, he detested.52
However, as a stimulus to the idea of natural selection, Malthus’s arguments
were central to the development of both Darwin’s and Wallace’s thought. In
Wallace’s case, it was in 1858, while fighting a malarial fever in Ternate, Indonesia,
that he recalled Malthus’s arguments and realized a struggle for scarce resources
could provide a mechanism for evolution.53 In the mid-nineteenth century it was
still highly risky to advocate a view of life’s origins that left no requirement for
God. Although Darwin developed his own version of natural selection as early
as 1838, he held back from publishing this, partly out of an obsessive desire to
work out every last little theoretical detail, but also out of fear of how going
public would affect his respectable position in society.54 Wallace had no such
qualms, and in June 1858 he wrote to Darwin with an outline of his new idea,
and a request to review his theory and then send it to the geologist Charles Lyell,
who, ironically, had been secretly urging Darwin to publish his work.53 For
Darwin, the letter arrived like a bombshell, for, as he observed to Lyell, ‘if
Wallace had my manuscript sketch written out in 1842, he could not have
made a better short abstract! . . . So all my originality, whatever it may amount
to, will be smashed.’55

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Instead, a compromise was arranged by Lyell and others in the scientific

establishment, whereby both men’s views on the subject were presented at a
meeting of the Linnean Society in London in July 1858.54 Neither Darwin nor
Wallace attended this, the former being ill and the latter still in Indonesia, and the
meeting drew surprisingly little attention at the time. Instead, it was the best-
selling Origin of Species, published in November 1859, that both introduced the
theory to a wider public, and ensured its primary association with Darwin.
However, another reason for the relative lack of public recognition of Wallace’s
contribution may also be his unwillingness to follow the theory through to its
logical conclusion and apply it to the origin of human consciousness. So while
Darwin did this in 1871 in The Descent of Man, where he proposed that humans are
‘descended from a hairy, tailed quadruped, probably arboreal in its habits’,56
Wallace appealed to supernatural mechanisms to explain humanity’s unique
mental attributes. In some ways, Wallace was too sophisticated for his own
good. At a time when even the liberal Darwin could view the native peoples of
the countries he visited as ‘degraded savages’, Wallace argued that all human
beings are essentially equal.57 Indeed, he counterposed the morality of the ‘primi-
tive’ people he encountered to the ‘social barbarism’ of Victorian England, and
their harmonious coexistence with nature to the environmental destruction being
wreaked by the Industrial Revolution.
This positive view of human potential led Wallace to wonder why, if the
complexities of the human mind were a product of blind chance, people living
in primitive settings had the same mental capabilities as those in the civilized
world. To him, this implied that the great part of human intelligence in such an
environment went unused. To explain this conundrum, Wallace concluded that
‘some higher intelligence directed the process by which the human race was
developed’,58 much to the dismay of Darwin, who told Wallace, ‘I hope you
have not murdered too completely your own and my child!’59 So it was that
Darwin, the bourgeois gentleman, proved more revolutionary than Wallace, the
socialist.
Despite its success, the theory of natural selection as expounded by either Darwin
or Wallace faced a major problem: the lack of a proper explanation for how new
characteristics are passed down to offspring so that those more appropriate for
survival in a new environment come to predominate. At this time, human offspring,
like animals or plants, were known to share many characteristics with their parents,

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