Inheritance: How Our Genes Change Our Lives--and Our Lives Change Our Genes

by Moalem MD PhD, Sharon

  Your thoughts, too, are constantly impacting your genes, which must shift and change, over time, to align your cellular machinery with the expectations you’ve set and experiences you’ve had. You’re creating memories. Emotions. Anticipation. All of that gets encoded, like an annotation in the margin of an old book, within all of our cells. The hundreds of trillions of synapses in your brain that make this happen are all simply junctions between neurons and cells, and the signals used to communicate must be replaced over time and fed with minuscule doses of chemicals created by your body. And many of our neurons are on the lookout to make new connections as well as maintaining ones that are decades old.

  This all happens in response to the demands of your life.

  And all of that changes you. Maybe it’s just the difference between an appoggiatura and a sixteenth note. Maybe it’s even more negligible than that.

  But through the flexibility of expression, your life has just changed genetic tunes.

  Feeling special? You should. But hold on to your humility, too. Because as we’re about to see, these sorts of changes can be seen in all sorts of life forms, large and small. Nor is it just living creatures that can modulate how they respond to life’s challenges. Many corporations have employed exactly the same strategies to control their markets or modulate their productions.

  As we’re about to see, some of these strategies were drawn up long before you were born, and yet they still come into play every time someone gets down on one knee. It’s time for me to propose another way to understand the flexibility of genetic expression.

  If you’re in the market for your first shiny rock, or if you’re looking for an upgrade, then you might like to know a little secret about the diamond business: Unlike a lot of other types of gemstones, diamonds are actually not all that rare.

  It’s true. There are lots of diamonds. Lots and lots of them. Big ones. Small ones. Blue, pink, and black. They’re mined in dozens of countries and on every continent except Antarctica, although Australian researchers have recently reported finding kimberlite, a type of volcanic rock often rich in diamonds, near the South Pole, so perhaps it’s only a matter of time.11

  Now, if you’ve ever spent a few paychecks on a diamond, and if you know anything about supply and demand, this might not make a lot of sense. If there are so many diamonds out there, after all, why are they so expensive?

  You can thank De Beers for that.

  The controversial company, which was founded in 1888 and is headquartered in the grand duchy of Luxembourg, has one of the largest inventories of sparkling stones in the world—most of which have been stashed away. Controlling the process from mining to production to processing to manufacturing, De Beers maintained a near worldwide monopoly on the diamond exchange for generations, releasing just the right amount of product into the market at just the right time so as to keep prices up and the market stable—and ensuring that a relatively common rock remained precious in the eyes (and wallets) of its beholders.12

  Savvy marketing tricks have done the rest. Before World War II, very few people exchanged engagement rings—and diamonds were just one of many kinds of stones that might be on them. But in 1938, De Beers hired a Madison Avenue adman by the name of Gerold Lauck to figure out how to persuade young men that a shiny piece of well-compressed carbon was the only way to express an intention of betrothal to a prospective mate. And by the early 1940s, Lauck’s marketing magic had managed to convince a good segment of the Western world that diamonds are indeed a girl’s best friend.13

  The industrialist Henry Ford would have loved to corner the market in that way. He certainly may have conspired to do so, but Ford’s product and its production were so complicated at the time that he had no choice but to deal with a lot of suppliers.

  That frustrated Ford to no end. The People’s Tycoon, as he was known, was perhaps the world’s first famous disciple of industrial efficiency—which we now can understand is rooted in many of the same strategies exploited by our genomes through genetic expression. Not surprisingly, Ford spent a lot of time working on streamlining the process as much as possible.

  “We have found in buying materials that it is not worthwhile to buy for other than immediate needs,” Ford wrote in his 1922 book, My Life and Work. “We buy only enough to fit into the plan of production, taking into consideration the state of transportation at the time.”14

  Alas, Ford lamented, the state of transportation was far from perfect. If it were perfect, he said, “…it would not be necessary to carry any stock whatsoever. The carloads of raw materials would arrive on schedule and in the planned order and amounts, and go from the railway cars into production. That would save a great deal of money, for it would give a very rapid turnover and thus decrease the amount of money tied up in materials.”

  Ford’s words were prescient, but he went to his grave without solving this problem. Eventually, Japanese car manufacturers were responsible for making great leaps in a system of production that tied the supply chains to immediate demand, a process we now know as just in time, or JIT, production. The business lore is that executives from Toyota were exposed to JIT while in the United States in the 1950s—not by the American car companies that they were visiting at the time, but rather during a side trip to the first self-service grocery store called the Piggly Wiggly. One of the grocery chain’s novel approaches was to have inventory automatically restocked as soon as it was removed from the shelf.15

  There are many benefits to employing this type of technique—chiefly, when done right, it can be a major moneymaker and saver. Of course, it’s not without its risks, one of the biggest being that the entire process becomes susceptible to supply shocks, events such as natural disasters or worker strikes that can interrupt delivery of raw materials and, in doing so, leave a factory completely idle and customers empty-handed.

  Apple experienced another of the drawbacks associated with JIT manufacturing: An unprecedented wave of demand for iPad Minis almost drowned out the company’s ability to produce the product when it couldn’t get the materials to make them into its factories fast enough.

  Understanding how businesses employ certain strategies similar to genetic expression can help us understand the biological strategies used by most of our cells to keep the costs of living down. Just like corporations, our bodies employ an unforgiving bottom line. Doing this makes the likelihood of our continued existence possible.

  And in that regard, we employ more of a Costco model of operations than a Walmart one. Since there’s a biological cost every time we use our genes to make anything, we aim to get the most out of what we make. Just like Costco does with its employees, our biology is configured for higher labor productivity—meaning we aim to have the smallest number of enzyme employees for the jobs we need to get done. Enzymes behave like microscopic molecular machines and are an example of structures that are coded for by our genes. Some enzymes are able to speed up chemical processes, while others like pepsinogen, when activated, help us digest our proteinaceous meals. Other enzymes, such as those that belong to the P450 family, detoxify poisons we may be knowingly or unwittingly consuming.

  We generally only produce what we need when we need it and try to keep what we store to a minimum. And we do that through genetic expression.

  Just like diamonds, which take millions of years and a whole lot of pressure to create, enzymes are biologically expensive to produce. To mitigate the cost of production, many of our enzymes can be induced. Which means that, when we need certain enzymes, our bodies can marshal up more of their resources to produce more of them on call, churning out the biological equivalent of iPad Minis to meet an increased demand. You may have inherited the genes for an enzyme, but that doesn’t always ensure that your body will use it.

  There’s a good chance you’ve experienced this at some point in your life, unaware of your active role in the process. If you’ve ever binged on alcohol—over a long holiday weekend, perhaps—then you’ve been there. In response to y
our partying, your liver cells worked overtime to make all the enzymes they needed to deal with that unexpected deluge of margaritas.

  The means of increasing production to meet demand—in this case alcohol dehydrogenase to break down ethanol—are always there, latent in your liver cells, ready for your next binge. But it may not be stored in large quantities, because just like extra parts sitting around on the factory floor, enzymes not only take up space but are costly to produce and maintain when you’re not drinking to excess.

  Almost all of the biological world is driven in the same way to streamline the cost of living. And it needs to be. Spend all your energy on enzymes you’re not going to use, and you’d be diverting precious resources from other daily concerns, like the continual process of brain plasticity.

  Astronauts provide a great example of this. Soon after arriving on the International Space Station, their hearts shrink by as much as a quarter of their original size.16

  In the same way that trading in a supercharged 300-horsepower Ford Mustang for a Mini Cooper with less than half the ponies would save you a whole lot of money at the gas station, the weightless environment of space means astronauts don’t need as big a cardiac engine.* But that’s also why, upon returning to Earth and reexperiencing gravity, space travelers often become light-headed and sometimes black out: Their hearts, like a Mini trying to scale a steep mountain road, just can’t push enough blood—and the crucial oxygen it carries—up to the brain.

  You don’t need to travel up to the space station for your heart to shrink. Just a few weeks in bed are all you need for it to begin to atrophy.17 But our bodies are also quite amazing at recovery—we just have to convince them that we need the power. And that’s not always a tough sell, because our cells are incredibly malleable. What we do every day makes a big difference in what our genes tell them to do—which is just another genetic motivation for you to get off the couch.

  Before we leave genetic expression, there’s just one more thing I’d like us to explore together.

  At first glance, Ranunculus flabellaris might not seem like that big a deal. The yellow water buttercup, which grows prolifically in forested wetlands in the United States and southern Canada, isn’t much to look at. Yet what you’re looking at, when you find one, is a plant that can completely change its appearance depending on how close it finds itself to water, a behavior we call heterophylly.

  The buttercup usually grows along a riverbank, which can be a precarious place for a plant to be as rivers are prone to overflow from season to season. That could be deadly for a delicate little flower like this one, but living on the edge of this habitat doesn’t deter this plant. Rather, it allows it to thrive, because genetic expression gives it the ability to completely change the shape of its leaves—from rounded blades to threadlike hairs that can float if the river spills over its banks.18

  When this change happens, the buttercup’s genome stays the same. To a passerby, it might look like a completely different plant, but deep inside, its genes haven’t changed. Only its expressed phenotype, or observable appearance, is altered.

  And just as an astronaut’s body can go from Mustang to Mini Cooper and back again, based on the conditions in which they live, another change in environment for the buttercup—the height of the river decreasing with the changing season—switches the plant back to the previous type of leaf growth. It’s all a matter of survival.

  Expression is just one of many strategies that plants, insects, animals, and even humans employ to deal with the rigors of life. In all of them, though, one thing is key: flexibility.

  What we are now learning is that our genes are part of a larger flexible network. This is contrary to much of what we’ve been told about our genetic selves. Our genes aren’t as fixed and rigid as most of us have been led to believe. If they were, we wouldn’t be able to adjust—just like the yellow water buttercup does—to the ever-changing demands of our lives.

  The thing Mendel couldn’t see in his peas—and that generations of geneticists continued to miss after his death—is that it’s not only what our genes give to us that’s important, but also what we give to our genes. Because, as it turns out, nurture can and does trump nature.

  And as we are about to see, it happens all the time.

  * Variable expressivity is a measurement of the extent or degree to which one is affected by a genetic mutation or condition.

  * Our hearts use a lot of energy to move our blood against the pull of gravity. If we’re in orbit, our blood becomes weightless, and then we can get the same degree of circulation with a lot less force. Which is why in space we can get away with having a much smaller heart.

  Chapter 3

  Changing Our Genes

  How Trauma, Bullying, and Royal Jelly Alter Our Genetic Destiny

  Most people know about Mendel’s work with peas. Some have heard of his truncated work with mice. But what most people don’t know is that Mendel also worked with honeybees—which he called “my dearest little animals.”

  Who can blame him for such adulation? Bees are endlessly fascinating and beautiful creatures—and they can tell us a lot about ourselves. For instance, have you ever been witness to the awesome and fearsome sight of an entire colony of bees swarming and on the move? Somewhere in the middle of that ethereal tornado is a queen bee that has left the hive.

  Who is she to deserve such a grand parade?

  Well, just look at her. For starters, just like human fashion models, queens have longer bodies and legs than their sister workers. They’re more slender and have smooth, rather than furry, abdomens. Because they often need to protect themselves from entomological coups from younger royal upstarts, queen bees have stingers that can be reused on demand, unlike female worker bees, who die after using their stingers just once. Queen bees can live for years, though some of their workers live only a few weeks. They can also lay thousands of eggs in a day, while all their royal needs are tended to by sterile workers.*

  So yeah, she’s kind of a big deal.

  Given the incredible differences between them, you could easily assume that queens differ genetically from the workers. That would make sense—after all, their physical traits differ considerably from their sister worker bees. But look deeper—DNA deeper—and a very different story emerges. The truth is that, genetically speaking, the queen is nobody special. A queen bee and her female workers can come from the same parents, and they can have completely identical DNA. Yet their behavioral, physiological, and anatomical differences are profound.

  Why? Because larval queens eat better.

  That’s it. That’s all. The food they eat changes their genetic expression—in this case through specific genes being turned off or on, a mechanism we call epigenetics. When the colony decides it’s time for a new queen, they choose a few lucky larvae and bathe them in royal jelly, a protein- and amino acid–rich secretion produced by glands in the mouths of young worker bees. Initially, all larvae get a taste of royal jelly, but workers are quickly weaned. The little princesses, however, eat and eat and eat until they emerge as a blue-blooded brood of elegant empresses. The one who murders all the rest of her royal sisters first gets to be queen.

  Her genes are no different. But her genetic expression? Royal.1

  Beekeepers have known for centuries—maybe longer—that larvae bathed in royal jelly will produce queens. But until the genome for the western honeybee, Apis mellifera, was sequenced in 2006, and the specific details of caste differentiation were worked out in 2011, no one knew exactly why.

  Like every other creature on this planet, bees share a lot of genetic sequences with other animals—even us. And researchers quickly noticed that one of these shared codes was for DNA methyltransferase, or Dnmt3, which in mammals can change the expression of certain genes through epigenetic mechanisms.

  When researchers used chemicals to shut down the Dnmt3 in hundreds of larvae, they got an entire brood of queens. When they turned it back on in another batch of larvae, the
y all grew to be workers. So rather than having something more than their workers, as might be expected, queens actually have a little less—the royal jelly the queens eat so much of, it appears, just turns down the volume on the gene that makes honeybees into workers.2

  Our diet differs from that of bees, of course, but they (and the clever researchers who study them) have given us lots of amazing examples of how our genes express themselves to meet the demands of our lives.3

  Like humans who fill a series of set roles during their lives—from students to workers to community elders—worker bees also follow a predictable pattern from birth to death. They start as housekeepers and undertakers, keeping the hive clean and, when necessary, disposing of their dead siblings to protect the colony from disease. Most then become nurses, working together to keep tabs on each larval member of the hive more than a thousand times a day. And then, right around the ripe old age of two weeks, they set off to forage for nectar.

  A team of scientists from Johns Hopkins University and Arizona State University knew that sometimes, when more nurse bees are needed, foraging bees will go back to do that job. The scientists wanted to know why. So they looked for differences in gene expression, which can be found by searching for chemical “tags” that rest atop certain genes. And indeed, when they compared the nurses with the foragers, those markers were in different places on more than 150 genes.

  So they played a little trick. When the foragers were off searching for nectar, the researchers removed the nurses. Not willing to permit their young ones to be neglected, upon their return the forager bees immediately reverted to nurse duties. And just as immediately, their genetic tagging pattern changed.4

  Genes that weren’t being expressed before, now were. Genes that were, now weren’t. The foragers weren’t just doing another job—they were fulfilling a different genetic destiny.