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Notes from "Genome: The Autobiography of a Species in 23 Chapters"

These are my notes from "Genome: The Autobiography of a Species in 23 Chapters" by Matt Ridley. Matt is one of my favorite authors. In this book he describes what the genome is, what it does, and what it means for us. There is some technical biochemistry, but also practical takeaways. He explores how genes work with the brain and personality, nature vs nurture, and what we have control over in our lives, health, and behavior. If you want to understand the code that you're written in, this is the book to read!

Chapter 1

The human genome is the instructions for how to build and run a human body.

Chapter 2

The human genome comes packaged in 23 separate sets of chromosomes. Of these, 22 pairs are numbered in approximate order of size, from largest (number 1) to the smallest. The remaining pair consists of the sex chromosomes: 2 large X chromosomes in women, 1 large X and 1 small Y in men.

Chapter 3

Each of the cells in our bodies contain 2 complete sets of the human genome located in the nuclei. The exceptions are egg and sperm cells, which have 1 copy each, and red blood cells, which have none. One copy of the genome came from the mother, and one from the father.

Imagine the genome is a book. There are 23 chapters called chromosomes. Each chapter contains several thousand stories called genes. Each story is made up of paragraphs called exons, which are interrupted by advertisements called introns. Each paragraph is made up of words called codons. Each word is written in letters called bases. There are 1 billion words in the book.

RNA can carry the same strand of letters as DNA, except that it uses U instead of T.

Chains of amino acids fold themselves up and are then know as proteins. Almost everything in the body, from hair to hormones, is either made of proteins or made by them. Every protein is a translated gene. In particular, the body chemical reactions are catalyzed by proteins known as enzymes. Even the processing, photocopying, error correction, and assembly of DNA and RNA molecules themselves, replication and translation, are done with the help of proteins. Proteins are also responsible for switching genes on and off by physically attaching themselves to promoter and enhancer sequences near the start of the gene's text. Different genes are switched on in different parts of the body. When genes are replicated, mistakes are sometimes made. This is know as mutation. Many mutations are neither harmful nor beneficial. There are 64 codons and only 20 amino acids, so many DNA words share the same meaning. Human beings accumulate about 100 mutations per generation.

Not all genes live inside the 23 chromosomes. A few live inside mitochondria.

Not all DNA spells out genes. Most of it is a jumble of repetitive or random sequences that is rarely or never transcribed – the so called "junk DNA."

Chapter 4

Life consists of two very different skills: the ability to replicate and the ability to create order.

Rabbits (or any living thing) do not defy the second law of thermodynamics, which says that in a closed system everything tends from order towards disorder, because rabbits are not closed systems. They build packets of order and complexity called bodies, but at the cost of expending large amounts of energy. In Ervin Shrödinger's phrase, "living creatures drink orderliness from the environment. The key to both of these features of life is information. The ability to replicate is made possible by the existence of a recipe.

Anything that can use the resources of the world to get copies of itself made, is alive.

Claude Shannon's idea is that information and entropy are opposite faces of the same coin and that both have an intimate link with energy. The less entropy a system has, the more information it contains. The reason a steam engine can harness the energy from burning coal and turn it into rotary motion is because the engine has high information content, information injected into it by its designer. So does a human body. Life too is digital information, written in DNA.

Life consists of an interplay of two kinds of chemicals: proteins and DNA. Protein represents chemistry - living, breathing, metabolism, and behavior - what biologists call the phenotype. DNA represents information - replication, breeding, sex - what biologists call the phenotype. Neither can exist without the other.

The genetic code consists of 3 letter words, each spelling out a particular 1 of 20 amino acids as part of a recipe for a protein. And so was born a more sophisticated creature that stored its genetic recipe on DNA, made its working machines in protein, and used RNA to bridge the gap between them.

Chapter 5

Natural Selection is the process by which genes change their sequences.

Chapter 8

Most asthmatics are also allergic to something. Asthma, allergies, eczema, and anaphylaxis are all part of the same syndrome caused by the same mast cells in the body alerted and triggered by the same immunoglobulin E molecules.

Our immune systems are set up in such a way that they expect to be educated in early childhood by soil mycobacteria, and when they're not the result is an unbalanced system prone to allergy.

The one thing you can't argue is that asthma is on the increase because asthma genes are on the increase.

Simplicity piled upon simplicity creates complexity.

Chapter 9

No study of the causes of intelligence has failed to find a substantial heritability.

Not only does your IQ change with age, but so does its heritability. As you grow up and accumulate experiences, the influence of your genes increases. As you grow up, you gradually express your own innate intelligence and leave behind the influences stamped on you by others. You select the environments that suit your innate tendencies, rather than adjusting your innate tendencies to the environments you find yourself in. This proves two vital things: that genetic influences are not frozen at conception, and that environmental influences are not inexorably cumulative. Heritability does not mean immutability.

The evidence suggests that exposing children to more expensive tuition has a dramatic effect on their IQ scores, but only temporarily. By the end of elementary school, children who have been in head-start programs are no further along than children who have not.

Heritability will have a greater effect in an egalitarian society than in an unequal one. Indeed, the definition of a perfect meritocracy, ironically, is a society in which people's achievements depend on their genes because their environments are equal.

Chapter 10

On chromosome 7 there lies a gene that plays an important role in equipping human beings with an instinct, and an instinct that lies at the heart of all human culture.

Chapter 11

Everybody gets an X chromosome from his or her mother. But if you inherited a Y chromosome from your father, you're a man. If you inherited an X chromosome from your father, you're a woman. The reason color blindness, hemophilia, and some other disorders are much more common in men is that these genes are on the X chromosome. Since men have no spare X chromosome, they're much more likely to suffer from these recessive problems than women.

Chapter 12

"We are survival machines - robot vehicles blindly programmed to preserve the selfish molecules known as genes." - Richard Dawkins, The Selfish Gene

Mother nature concealed a dirty little secret in the genome. Each gene is far more complicated than it needs to be.

97% of the genome does not consist of true genes at all. It consists of a menagerie of strange entities called pseudogenes, retropseudogenes, satellites, mini satellites, micro satellites, transposons, and retrotransposons. All collectively known as "junk DNA" and sometimes as "selfish DNA".

The commonest protein recipe in the entire human genome is the gene for a protein called reverse transcriptase. Reverse transcriptase is a gene that serves no purpose at all, so far as the human body is concerned. If every copy of it were carefully and magically removed from the genome of a person at the moment of conception, the person's health, longevity, and happiness would be more likely to be improved than damaged. Reverse transcriptase is vital for a certain type of parasite.

A good many of the copies of the reverse transcriptase gene in the human genome are there because recognizable retroviruses put them there, either long ago or even relatively recently. There are several thousand nearly complete viral genomes integrated into the human genome, most of them now inert or missing a human gene. These inert human endogenous retroviruses, or HERVs, account for 1.3% of the entire genome.

About 35% of our DNA is made of "selfish DNA" which means that replicating its genes takes 35% more energy than it needs.

What we see in the human genome is not some rapidly advancing parasitic infection, but the dormancies of many past parasites, each of which spread rapidly until the genome found a way of suppressing, but not excising it.

Chapter 13

Wherever you look, reasons behind genetic variability seem to have something to do with infectious disease.

Roughly 40% of Europeans have type O blood, 40% have type A blood, 15% have type B blood, and 5% have type B blood. The proportions are similar in other continents.

For blood type genes, if it becomes rare, it comes back into fashion. This is known as frequency-dependent selection, and it seems to be the commonest reason we are all so genetically diverse.

Men and women most prefer, or least dislike, the body odor of members of the opposite sex who are most different from them genetically.

The Human Genome Project was founded upon a fallacy. There is no such thing as "the" human genome, neither in space nor in time, can such a definite object be defined. There are genes that differ from person to person.

Genomes change. Different versions of genes rise and fall in popularity, driven often by the rise and fall of diseases. There is a regrettable human tendency to exaggerate stability, to believe in equilibrium. The genome is a dynamic changing scene.

The genome that we decipher in this generation is but a snapshot of an ever changing document. There is no definitive edition.

Chapter 14

The genome is a scripture in which is written the past history of plagues.

No gene is an island. Each one exists as part of an enormous confederation called the body.

The brain, the body, and the genome are locked, all three, in a dance. The genome is as much under the control of the other two as they are controlled by it. That is partly why genetic determinism is such a myth. The switching on and off of human genes can be influenced by conscious and unconscious external action.

One of cortisol's most surprising effects is that is suppresses the workings of the immune system.

The status of a person's job is more likely to be predictable of a heart attack than obesity, smoking, or high blood pressure.

If the brain responding to psychological stress stimulates the release of cortisol, and cortisol suppresses the reactivity of the immune system, then a dormant viral infection may well flare up or a new one catch hold. The symptoms may indeed be physical, and the causes psychological. If a disease affects the brain and alters the mood, causes may be physical and the symptoms psychological. This topic is known as psychoneuroimmunology.

Far from behavior being at the mercy of our biology, our biology is often at the mercy of our behavior.

Chapter 15

The brain works by electrical signals that cause chemical signals that cause electrical signals.

Your brain chemistry is determined by the social signals to which you're exposed. Biology determines behavior, yet is determined by society.

Chapter 16

The homeobox is the bit by which the protein made by the gene attaches to a strand of DNA to switch on or off another gene. All homeotic genes are for switching other genes on and off.

Chapter 17

One way to get around the problem of lactose intolerance is to let bacteria digest the lactose and turn the milk into cheese.

Chapter 18

There is a gene on chromosome 14 called TEPI. The product of TEPI is a protein, which forms a part of an unusual little biochemical machine called telomerase. Lack of telomerase causes senescence. Addition of telomerase turns certain cells immortal. James Watson (DNA's co-discoverer) noticed that the biochemical machines that copy DNA, called polymerases, can't start at the very tip of the DNA strand. They need to start several words into the text. Therefore, the text gets a little shorter each time it's duplicated. Imagine a photocopier that makes perfect copies of your text, but always starts with the second line of each page and ends with a penalty applied. The way to cope with such a maddening machine would be to start and end each page with a line of repeated nonsense you don't mind losing. This is exactly what chromosomes do. Each chromosome is just a giant super-coiled foot-long DNA molecule, so it can all be copied, except the very tip of each end. At the end of every chromosome there occurs a repeated stretch of meaningless text. The word TTATTG repeated again and again about 2000 times. This stretch of terminal tedium is known as a telomere. Its presence allows the DNA copying devices to get started without cutting short any sense-containing text. Like and aglet, the little plastic bit on the end of a shoelace, it stops the end of the chromosome from fraying. But every time the chromosome is copied a little bit of the telomere is left off. After a few hundred copyings, the telomere is getting so short at the end, that meaningful genes are in danger of being left off. In your body the telomeres are shortening at a rate of about 31 letters a year. More in some tissues. That's why cells grow old and cease to thrive beyond a certain age. It may be why bodies too grow old. The reason that genes do get left off in egg cells and sperm cells, the direct ancestors of the next generation, is the presence of telomerase, whose job it is to repair the frayed ends of chromosomes, re-lengthening the telomeres.

The lack of telomerase seems to be the principle reason why cells grow old and die. But is it the principle reason bodies grow old and die? There is some good evidence in favor. Cells in the walls of arteries generally have shorter telomeres than cells in the walls of veins. This reflects the harder lives in cells in the artery walls that are subject to more stress and strain because arterial strain of blood in under higher pressure. They have to expand and contract with every pulse beat, so they suffer more damage and need more repair. Repair involves cell copying, which uses up the ends of telomeres. Cells start to age, which is why we die of hardened arteries, not from hardened veins. The aging of the brain can't be explained so easily because brain cells don't replace themselves so easily. The brain's support cells, called glial cells, do indeed duplicate themselves. Their telomeres do therefore probably shrink. However, there are very few expert who believe that aging is chiefly due to senescent cells - cells with abridged telomeres. Most of the things we associate with aging - cancer, muscle weakness, tendon stiffness, hair grayness, changes in skin elasticity - have nothing to do with cells failing to duplicate themselves. In the case of cancer, the problem is that cells are copying themselves all too enthusiastically.

Every animal has roughly the same number of heartbeats per lifetime. There are a few exceptions, notably bats and birds.

Natural selection carefully weeds out all genes that might cause damage to the body before or during reproduction. Natural selection can't weed out the genes that cause damage to the body after reproductive age, because there is no reproduction of the successful in old age.

The evolutionary theory of aging explains all across species trends in a satisfying way. It explains why slow aging species tend to be large (elephants) or well protected (tortoises, porcupines) or relatively free from natural predators (bats, sea birds). In each case, because the death rate from accidents or predation is low, so the selective pressure is high for the versions of genes that prolong health into later life. Human being of course have been large, well protected, and have few predators for centuries, so we age slowly.

Aging is turning out to be one of those things that is under the control of many genes. Aging is the more or less simultaneous deterioration of the body's systems.

Free oxygen is dangerous stuff. Our bodies are continually "rusting" from the continual effects of oxygen. Most of the mutations that cause longevity, at least in flies and worms, turn out to be in genes that inhibit the production of free radicals. That is, they prevent the damage being done in the first place, rather than prolong the replicating life of cells that repair the damage.

Cancer is the quintessential disease of aging. Cancer rates rise steadily with age. There is no creature on earth that is less likely to get cancer in old age than in youth. The prime risk factor for cancer is age. Other risk factors such as smoking work in part by accelerating aging. Tissues that are prone to cancer tend to be tissues that do a lot of cell division throughout life. So we have a paradox. Shortened telomeres mean higher cancer risk. But telomerase, which keeps telomeres long, is necessary for a tumor. The resolution lies in the fact that the switching on of telomerase is one of the essential mutations that must occur if a caner is to turn malignant.

Chapter 19

Male behavior is systematically different from female behavior in most species, and the difference has an innate component. The brain is an organ with an innate gender.

Chapter 20

Here on chromosome 16 lie genes that allow for learning and memory. We human beings may be determined by surprising extent by our genes, but we're even more by what we've learned in our lifetimes. The genome has found it helpful to invent a much faster machine than natural selection, whose job it is to extract information from the world in a matter of minutes or seconds and embody that information in behavior – the brain.

Learning is the opposite of instinct. Instinct is genetically determined behavior. Learning is behavior modified by experience.

Chapter 21

In ever tissue, everyday, there is a cell that breaks ranks and decided to divide again. If the cell can't be stopped, we call the result cancer. Usually it can be stopped. The problem of cancerous mutiny is so old that all large bodied animals the cells are equipped with an elaborate series of switches designed to induce the cell to commit suicide if it should find itself turning cancerous. The most famous of these switches is called TP53, which lies on the short arm of chromosome 17.

Genes alone can cause cancer. Oncogenes are genes that encourage cells to grow. Tumor suppressor genes are the opposite of oncogenes. Whereas oncogenes cause cancer if they're jammed on, tumor suppressor genes cause cancer if they're jammed off. A tumor must contain a cell that contains a jammed on oncogene and a jammed off tumor suppressor gene. To escape and grow uncontrollably, the tumor must now pass by an even more determined checkpoint manned by a gene that detects abnormal behavior in a cell and issues instruction to different genes to dismantle the cell from the inside. This is TP53.

Detecting cancer early is so important. The larger a tumor becomes, the more likely it is to suffer the next mutation, both because of general probability and because the rapid proliferation inside the tumor can lead to genetic mistakes, which can cause mutations.

Inside a growing ball of cancer cells, the blood supply can run short, so the cells begin to suffocate. Malignant cancers get over this problem by sending out a signal to the body to grow new arteries into the tumor.

So important is apoptosis that almost all therapeutic cancer treatments work only because they induce apoptosis by alerting P53 and its colleagues.

A major branch of medicine has been acting under misapprehension. Instead of looking for agents that kill dividing cells, doctors should have been looking for agents that encourage cell suicide. That doesn't mean chemotherapy has been wholly ineffective, but it has been effective only by accident. Now that medical research knows what it's doing the results should be more promising.

There is now, for the first time in human history, a real prospect for a genuine cure for cancer. It has come from reductionist genetic research and the understanding that this brings.

Natural selection, once she has found a solution for solving one problem, frequently uses it to solve another. Apoptosis has other functions than the elimination of cancer cells. It's also useful in the fight against ordinary infectious disease. If a cell detects it's been infected with a virus, it can kill itself for the good of the body as a whole.

Chapter 22

We are for the first time in the position of being able to edit the text of our genetic code.

In 30 years of genetic engineering no public accident, big or small, has resulted from a genetic engineering experiment.

A retrovirus contains a message written in RNA which reads, in essence, "make a copy of me and stitch it into your chromosome." All a gene therapist need do is take a retrovirus, cut out a few of its genes, especially those that make it infectious after the first insertion, put in a human gene, and infect the patient with it. The virus goes to work inserting the gene into the cells of the human body, and lo, you have a genetically modified person.

The genes are literally shot into the cell onboard tiny particles of gold using gunpowder or particle accelerators. This technique has now become standard for all plant genetic engineering.

Putting a gene into an animal is now simple. You just stick it in. Suck your gene into the mouth of a very fine glass pipette, jab the tip of the pipette into a single cell mouse embryo, extract it from a mouse 12 hours after mating, make sure the tip of the pipette is inside of one of the cells two nuclei, and press gently. Transgenic mice allow scientists to figure out what genes are for and why.

Chapter 23

The improvement of any medical improvement confronts our species with a moral dilemma. If the technology can save lives, then not to develop it and use it is morally questionable, even if there are inherent risks.

The diagnostic symptom of Alzheimers is the appearance in brain cells of plaques.

"All disease is genetic, even when it's also something else." - Paul Berg

Chapter 24

Here in the prion gene we have respectable digital changes, substituting one word for another, yet causing changes that can't be wholly predicted without other knowledge. The prion system is analog, not digital. It is a change not of sequence, but of shape.

Chapter 25

Genetic screening is about giving private individuals private choices on private criteria. Eugenics is about nationalizing that decision to make people breed not for themselves, but for the state.

Chapter 26

Freedom equals the part of our nature not determined by our genes.

People get their personalities from their genes and their peers, not from their parents.

We have a paradox. Unless our behavior is determined, then it is random. If it is determined, then it's not free. Yet we feel and demonstrably are free.

If genes can affect behavior, and behavior can effect genes, then causality is circular. And in a systems of circular feedbacks hugely unpredictable results can follow from simple determinist processes. This kind of notion goes under the name of chaos theory.

Freedom is the ability to standup and transcend the limitations of the environment.

Freedom lies in expressing your own determinism. It's not the determinism that makes the difference, but the ownership.

Everyone has a completely unique endogenous nature – a self.


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