She Has Her Mother’s Laugh: The Powers, Perversions, and Potential of Heredity is available in paperback. This article, adapted from the book, originally appeared as the cover story in the May/June 2019 issue of Skeptical Inquirer.
If someone says, “I guess it’s in my DNA,” you never hear people say, “DN — what?” We all know what DNA is, or at least think we do.
It’s been seven decades since scientists demonstrated that DNA is the molecule of heredity. Since then, a steady stream of books, news programs, and episodes of CSI have made us comfortable with the notion that each of our cells contains three billion base pairs of DNA, which we inherited from our parents. But we’ve gotten comfortable without actually knowing much at all about our own genomes.
Indeed, if you had asked to look at your own genome twenty years ago, the question would have been absurd. It would have been as ridiculous as asking to go to the moon. When scientists unveiled the first rough draft of the human genome in the early 2000s, the final bill came to an Apollo-scale $2.7 billion.
Since then, advances in DNA sequencing and software for analyzing genetic data have steadily brought down the price tag. By 2006, it cost only $14 million to sequence a single human genome. Even at that drastically reduced price, though, only a few big labs with major financial support would dare take on such an expensive project. But in the years that followed, DNA sequencing continued its exponential cost crash, becoming cheap enough to turn into a consumer product.
If you want to get your entire genome sequenced — all three billion base pairs in your DNA — a company called Dante Labs will do it for $699. You don’t need whole genome sequencing to learn a lot about your genes, however. The 20,000 genes that encode our proteins make up less than 2 percent of the human genome. That fraction of the genome — the “exome” — can be yours for just a few hundred dollars. The cheapest insights come from “genotyping” — in which scientists survey around a million spots in the genome known to vary a lot among people. Genotyping — offered by companies such as 23andMe and Ancestry — is typically available for under a hundred dollars.
Thanks to these falling prices, the number of people who are getting a glimpse at their own genes is skyrocketing. By 2019, over twenty-five million worldwide had gotten genotyped or had their DNA sequenced. At its current pace, the total may reach 100 million by 2020.
Future generations will look back at today as a pivotal moment in DNA’s cultural history. People are no longer thinking of their DNA as a black box but as a database to be mined. They’re learning that they have inherited mutations that raise their risk of certain diseases. They’re getting estimates of their ancestry based on genetic markers that are common in certain parts of the world. They’re merging their genetic information with genealogy to discover distant relatives. Some are also discovering some not-so-distant relatives that until now were family secrets.
There’s a lot we can learn about ourselves in these test results. But there’s also a huge opportunity to draw the wrong lessons.
Many people have misconceptions about heredity — how we are connected to our ancestors and how our inheritance from them shapes us. Rather than dispelling those misconceptions, our growing fascination with our DNA may only intensify them. A number of scientists have warned of a new threat they call “genetic astrology.” It’s vitally important to fight these misconceptions about heredity, just as we must fight misconceptions about other fields of science, such as global warming, vaccines, and evolution. Here are just a few examples.
Misconception #1: Finding a Special Ancestor Makes You Special
There are certain clubs to which ancestry is the key to admission. You can get into the Mayflower Society if you descend from the passengers of that famous ship. You can join the Order of the Crown of Charlemagne if you can prove that the Holy Roman Emperor is your ancestor. It’s a thrill to discover we have a genealogical link to someone famous — perhaps because that link seems to make us special, too.
But that’s an illusion. I could join the Mayflower Society, for example, because I’m descended from a servant aboard the ship named John Howland. Howland’s one claim to fame is that he fell out of the Mayflower. Fortunately for me, he got fished out of the water and reached Massachusetts. But I’m not the only fortunate one; by one estimate, there are two million people who descend from him alone.
Mathematicians have analyzed the structure of family trees, and they’ve found that the further back in time you go, the more descendants people had. (This is only true of people who have any living descendants at all, it should be noted.) This finding has an astonishing implication. Since we know Charlemagne has living descendants (thank you, Order of the Crown!), he is likely the ancestor of every living person of European descent. And if you could get in a time machine and travel back a few thousand years, you could find someone who was a common ancestor of all living people on Earth.
Misconception #2: You Are Connected to All Your Ancestors by DNA
When you look at your family tree, you’re looking at a series of branching lines that link you to your ancestors. What exactly flows down through those lines as they travel through time? A few centuries ago, people might say it was blood. In recent decades, blood has been replaced in our popular imagination with DNA. After all, our genes didn’t come out of nowhere. We inherited them.
But genetics do not equal genealogy. It turns out that practically none of the Europeans who descend from Charlemagne inherited any of his DNA. All humans, in fact, have no genetic link to most of their direct ancestors.
The reason for this disconnect is the way that DNA gets passed down from one generation to the next. Every egg or sperm randomly ends up with one copy of each chromosome, coming either from a person’s mother or father. As a result, we inherit about a quarter of our DNA from each grandparent — but only on average. Any one person may inherit extra DNA from one grandparent and less from another. If you go back to the next generation, you’ll find that each great-grandparent contributed approximately an eighth of your DNA — but, again, that’s only an average. Some of them may have contributed much more, others much less.
If you go back a few generations more, that contribution can drop all the way to zero. Graham Coop, a geneticist at the University of California, Davis, and his colleagues have calculated the odds of sharing no DNA with an ancestor as they moved back through the generations. If you go back ten generations, the odds of having DNA from any given ancestor drop to less than 50 percent. They go down even more as you push back further through your ancestry. While it is true that you inherit your DNA from your ancestors, that DNA is only a tiny sampling of the genes in your family tree.
Even without a genetic link, though, your ancestors remain your ancestors. They did indeed help shape who you are — not by giving you a gene for some particular trait, but by raising their own children, who then raised their own children in turn, passing down a cultural inheritance along with a genetic one.
Misconception #3: Ancestry Tests Are as Reliable as Medical Tests
Millions of people are getting ancestry reports based on their DNA. My own report informs me that I’m 43 percent Ashkenazi Jewish, 25 percent Northwestern European, 23 percent South/Central European, 6 percent Southwestern European, and 2.2 percent North Slavic. Those percentages sound impressive, even definitive. It’s easy to conclude that ancestry reports are as reliable as stepping on a scale at the doctor’s office to get your height and weight measured.
That is a mistake, and one that can cause a lot of heartbreak. To estimate ancestry, researchers compare each customer to a database of thousands of people from around the world. Those “reference populations” are typically selected because they have deep roots where they live. Some researchers select only people whose family has lived in the same place for three generations, for example. In each population, there are some genetic variants that are unusually common and others that are unusually rare. Researchers then look for these variants in a customer’s DNA. They can identify stretches of DNA that are likely to have originated in a particular part of the world. While some matches are clear-cut, others are less so. As a result, ancestry estimates always have margins of error — which often go missing in the reports customers get.
To gain more certainty in their estimates, scientists are building up bigger databases. In 2018, Ancestry.com unveiled a new set of estimates for its customers. They got a lot of backlash. People who had initially been thrilled to discover a small portion of their ancestry came from Italy or Cameroon were devastated to now learn that they had no such link at all.
These estimates are going to get better with time, but there’s a fundamental limit to what they can tell us about our ancestry. To say I am 43 percent Ashkenazi doesn’t have the same timeless truth as saying I’m 43 percent carbon. Carbon has been carbon for billions of years. But the Ashkenazi people emerged through history. In the Roman Empire, people of Near East and European ancestries came together and started having children. In the Middle Age, Jews in northern and eastern Europe began to be persecuted and formed increasingly isolated communities. In these small groups, children increasingly inherited the same set of genetic variants. From an estimated population of just 350 ancestors, the Ashkenazi population has now reached ten million. They all share a number of distinctive genetic markers from that period of history. But their history reaches farther back in time, to older peoples.
Researchers are getting glimpses of those older peoples by retrieving DNA from ancient skeletons. And they’re finding that our genetic history is far more tumultuous than previously thought. Time and again, researchers find that the people who have lived in a given place in recent centuries have little genetic connection to the people who lived there thousands of years ago. All over the world, populations have expanded and migrated, coming into contact with other populations. In Europe, for example, new waves of genetically distinct people have arrived from elsewhere every few thousand years, either replacing or interbreeding with the people who lived there before. Today, Europeans are genetically similar to each other, but only because the genes of their disparate ancestors — from places such as Africa, Turkey, and Russia — have been well mixed. If you want to find purity in your ancestry, you’re on a fool’s errand.
Misconception #4: There’s a Gene for Every Trait You Inherit
When we learn about genetics in school, we learn about Gregor Mendel. In the 1850s, Mendel crossed lines of pea plants and discovered that their traits — such as the color of their flowers or the texture of their peas — were carried by invisible hereditary factors. Some factors were dominant, meaning that inheriting just one copy of them determined a trait. Other factors were recessive, meaning that they could shape a pea plant if it inherited two copies.
Mendel is a great place to start learning about heredity but a bad place to stop. There are some traits that are determined by a single gene. Whether Mendel’s peas were smooth or wrinkled was determined by a gene called SBEI. Whether people develop sickle cell anemia or not comes down to a single gene called HBB. But many traits do not follow this so-called Mendelian pattern — even ones that we may have been told in school are Mendelian.
Consider your ear lobes. For decades, teachers taught that they could either hang free or be attached to the side of our heads. The sort of ear lobes you had was a Mendelian trait, determined by a single gene. In fact, our ear lobes typically fall somewhere between the two extremes of strongly attached to fully free. In 2017, a team of researchers compared the ear lobes of over 74,000 people to their DNA. They looked for genetic variants that were common in people at either end of the ear-lobe spectrum. They pinpointed forty-nine genes that appear to play a role in determining how attached they are to our heads. There well may be more waiting to be discovered.
None of those forty-nine genes is a gene “for” ear-lobe attachment. That language just doesn’t make sense for the way most genes work. The genes that the scientists identified become active in many cells in an embryo. Some are active in skin cells across the body. Some are active in hair and sweat glands as well. Some help build the intricate anatomy of the inner ear. The attachment of our ear lobes is the result of a symphony performed by these players.
The genetics of ear lobes is actually very simple compared to other traits. Studying height, for example, scientists have identified thousands of genetic variants that appear to play a role. The same holds true for our risk of developing diabetes, heart disease, and other common disorders. We can’t expect to find a single gene in our DNA tests that determines whether we’ll die of a heart attack. Nor should we expect easy fixes for such complex diseases by repairing single genes.
Misconception #5: The Genes You Inherit Explain Exactly Who You Are
Throughout our lives — through our successes and failures, through our joys and suffering — we often wonder how things turned out the way they did. The more that scientists explore our DNA, the easier it is to shrug and say that it was all programmed in our genes.
Take, for example, a recent study on how long people stay in school. Researchers examined DNA from 1.1 million people and found over 1,200 genetic variants that were unusually common either in people who left school early or in people who went on to college or graduate school. They then used the genetic differences in their subjects to come up with a predictive score, which they then tried out on another group of subjects. They found that in the highest-scoring 20 percent of these subjects, 57 percent finished college. In the lowest-scoring 20 percent, only 12 percent did.
But these results don’t mean that how long you stayed in school was determined before birth by your genes. Getting your children’s DNA tested won’t tell you if you should save up money for college tuition or not. Plenty of people in the educational attainment study who got high genetic scores dropped out of high school. Plenty of people who got low scores went on to get PhDs. And many more got an average amount of education in between those extremes. For any individual, these genetic scores make predictions that are barely better than guessing at random.
This confusing state of affairs is the result of how genes and the environment interact. Scientists call a trait such as how long people stay in school “moderately heritable.” In other words, a modest amount of the variation in education attainment is due to genetic variation. Lots of other factors also matter, too — the neighborhoods where people live, the quality of their schools, the stability of their family life, their income, and so on. What’s more, a gene that may have an influence on how long people stay in school in one environment may have no influence at all in another.
Misconception #6: You Have One Genome
In 2002, a woman named Lydia Fairchild applied for enforcement of child support when she separated from the father of her two children. The state of Washington required genetic testing to confirm his paternity. The tests showed he was indeed the father. But they also showed that Fairchild was not the mother.
State officials threatened to charge Fairchild with fraud, despite her protests that she had given birth to the children and the testimony of her mother, who had seen the birth of her grandchildren. When Fairchild went into a hospital to give birth to another child, a court official came to witness the delivery and watch the nurses draw blood for another DNA test. Once more, the test indicated that Fairchild was not the infant’s mother.
This absurd situation arose because of the common assumption that each of us carries a single genome. According to this assumption, you will find an identical sequence of DNA in any cell you examine. But there are many ways in which we can end up with different genomes within our bodies.
Fairchild is known as a chimera. She developed inside her mother alongside a fraternal twin. That twin embryo died in the womb, but not before exchanging cells with Fairchild. Now her body was made up of two populations of cells, each of which multiplied and developed into different tissues. In Fairchild’s case, her blood arose from one population, while her eggs arose from another.
Women can also become chimeras with their own children. During pregnancy, fetuses can shed cells that then circulate throughout a woman’s body. In some cases they linger on after birth. They can then develop into muscle, breast tissue, and even neurons.
It’s unclear how many people are chimeras. Once they were considered bizarre rarities. Scientists became aware of them only in cases such as Lydia Fairchild’s, when their mixed identity made itself known. In recent years, researchers have been carrying out small-scale surveys that suggest that perhaps a few percent of twins are chimeras, but the true number could be higher. As for chimeric mothers, they may be the rule rather than the exception. In a 2017 study, researchers studied brain tumors taken from women who had sons. Eighty percent of them had Y-chromosome-bearing cells in their tumors.
Chimerism is not the only way we can end up with different genomes. Every time a cell in our body divides, there’s a tiny chance that one of the daughter cells may gain a mutation. At first, these new aberrations — called somatic mutations — seemed important only for cancer. But that view has changed as new genome-sequencing technologies have made it possible for scientists to study somatic mutations in many healthy tissues. It now turns out that every person’s body is a mosaic, made up of populations of cells with many different mutations.
Misconception #7: Genes Don’t Matter Because of Epigenetics
The notion that our genes are our destiny can trigger an equally false backlash: that genes don’t matter at all. And very often, those who push against the importance of genetics invoke a younger, more tantalizing field of research: epigenetics.
Ask five scientists to define epigenetics and you may get five different definitions. But they will all center on the fact that genes, on their own, do nothing. They simply store information that our cells can use as guides for building proteins or RNA molecules. But our cells only use genes in response to certain combinations of signals. It can be disastrous to use genes at the wrong time or in the wrong place. Genes involved in making enamel need to be switched on in developing teeth. But you wouldn’t want your skin cells to make it too, trapping you in an enamel sarcophagus.
Our cells use many layers of control to make proper use of their genes. They can quickly turn some genes on and off in response to quick changes in their environment. But they can also silence genes for life. Women, for example, have two copies of the X chromosome, but in early development, each of their cells produces a swarm of RNA molecules and proteins that clamp down on one copy. The cell then only uses the other X chromosome. And if the cell divides, its daughter cells will silence the same copy again.
One of the most tantalizing possibilities scientists are now exploring is whether certain epigenetic “marks” can be inherited not just by daughter cells but by daughters — and sons. If people experience trauma in their lives and it leaves an epigenetic mark on their genes, for example, can they pass down those marks to future generations?
If you’re a plant, the answer is definitely yes. Plants that endure droughts or attacks by insects can reprogram their seeds, and these epigenetic changes can get carried down several generations. The evidence from animals is, for now, still a mixed bag. In one intriguing experiment, researchers separated male mouse pups from their mothers from time to time, causing them stress. Later, they used sperm from those stressed mice to fertilize eggs, and some of their descendants proved to be unusually sensitive to stress. But skeptics have questioned how epigenetics can transmit these traits through the generations, suggesting that the results are just statistical flukes. That hasn’t stopped a cottage industry of epigenetic self-help from springing up. You can join epigenetic yoga classes to rewrite your epigenetic marks or go to epigenetic psychotherapy sessions to overcome the epigenetic legacy you inherited from your grandparents.
You may feel more limber after your yoga class. And you may feel better after having talked about your anxiety. But your genes will still work much the same as they did before.
Copyright 2019 Carl Zimmer