It’s often said that humans are 99.9% identical. and what makes us unique is a measly 0.1% of our genome. This may seem insignificant. But what these declarations fail to point out is that the human genome is made up of three billion base pairs—which means 0.1% is still equal to three million base pairs.
In those three million differences lie the changes that give you red hair instead of blonde, or green eyes instead of blue. You can find changes that increase your risk of obesity, or others that decrease your risk of heart disease; differences that make you taller or lactose intolerant, or allow you to run faster.
When I first started learning about genetic variation, I assumed these changes—the 0.1% that make us unique—only appeared in certain places, such as genes for height or inherited diseases like diabetes. I thought the rest of the genome—the other 99.9%—was fixed; that the 0.1% that was different in me was more or less the same 0.1% that was different in you. But, as it turns out, the 0.1% of DNA that is different between people is not always the same 0.1%: Variation can happen anywhere in our genomes.
In fact, one group of scientists looking at 10,000 people found variants at 146 million unique positions, or about 4.8% of the genome. Another group collected the DNA from 15,000 people and found 254 million variants, roughly 8% of the genome. And as we continue to sequence 100,000, 100 million, or all seven billion people on the planet, we will find a lot more variation. This means that humans have many more differences than we first thought.
Imagine that your DNA is a car. There are certain obvious variants you can have: blue or white, two-door or four-door, convertible or sedan. These changes represent the 0.1%. Because the other 99.9%—the engine, the seats, the steering wheel, the tires—has to be there for the car to work, we assume they are fixed.
But electric cars have shown us that we don’t need the gas cap, the gas tank, or even a gas engine any more; we can replace those things with a variant like batteries and charging ports. And maybe one day we’ll develop cars that have boosters instead of tires so we can hover over the ground.
In other words, what we believe is static may actually be variable. More than 0.1% of the car can change and it still be a car, just like the human genome.
With the rise of services that offer to sequence your DNA, more and more people are talking about the value of personal genomics and what you might uncover about yourself. These kinds of mail-in tests are an easy way to point to something tangible—like your blue eyes or the waddle you and your grandmother share—and say “It runs in the family.” You might even say, “There’s a gene for that!”
But those examples of straight-forward, visible evidence are just starting points in the immense and only partially explored field of personal genomics. There are also many variations of our genomes that are invisible to the naked eye, like the way we metabolize caffeine, have a distaste for cilantro, or the more serious examples of predispositions toward certain types of cancers and diseases like Alzheimer’s and Parkinson’s.
There are also all sorts of other gene variants we haven’t discovered yet. Because our data is limited by the amount of sequenced DNA available for study, scientists like myself have only explored a small portion of the genetic variation that exists in the world.
As access to personal genomics becomes a more practical option and more people opt in to research, this data pool grows every day. This means our theories will become much less theoretical in the months and years to come, and it soon won’t be surprising to discover there’s a gene for almost every trait.
So what does all this variation actually mean? What do we learn by cataloging all this information?
The consequences of sequencing millions of people’s DNA and identifying new genetic variants are both simultaneously predictable and unknown. On the predictable side, we are going to learn a lot more about human health and disease: Individual genetic variants and groups of genetic variants will be found to play a role in obesity, heart disease, and cancer, among other factors. We are going to find genetic variants responsible for rare diseases that have gone undiagnosed.
But it’s the unknown findings that get me excited. We don’t know how many unique variants we will find. And while our current understanding of biology suggests some positions in DNA are not variable (because any change in these genes disrupts the basic function of being human), we may discover that these positions actually are variable and can change. We’re also getting to a point where we will be able to better study the role of environment—what you are exposed to, the things you choose to eat, the activities you decided to engage in—and how it interacts with your DNA. With this information, we will be able to better make predictions about you as an individual.
There is still so much for us to discover about human genetic variation. A variant that increases risk for a disease today might turn out to be protective for another disease tomorrow. The more people who get their DNA sequenced—whether for personal or research purposes—the more we will discover.
We each carry three billion base pairs of information inside us with the potential to unravel a piece of the mystery that makes us all so fundamentally human. At the end of the day, we are all still more similar than we are different—but we are just beginning to understand how important our differences are.
