What we do know is that human cells use an RNA gene called X inactive specific transcript, or XIST, which is found on the X chromosome and produces a scaffolding that covers the soon-to-be-silenced X chromosome from top to bottom. During this early phase of development, both X chromosomes are not silenced, and they both express XIST, but only one of them will eventually be subdued and silenced. Since male cells do not normally have more than one X chromosome, the process of X inactivation doesn’t have to occur within them.
So which of the two female X chromosomes becomes silenced? For the most part, the superior one of the two outwits XIST and stays active. I have had female patients, for example, who had an X chromosome that was damaged or abnormal, and within their cells this damaged X chromosome was always the one that was preferentially silenced and turned off. The XIST scaffolding works by squeezing and eventually condensing down and silencing the X chromosome into a structure called a Barr body.* Every female cell ends up having one active X chromosome and one silenced X chromosome in the form of a Barr body.
As in a good mixed martial arts (MMA) fight, only one X is left standing in each cell. If each of the X chromosomes is equal in this X inactivation match-up, then the silencing is thought to be random—like the result of a coin toss. This process ends with the silenced X chromosome or Barr body becoming inaccessible to the female cell. Or so we thought.
For most of the fifty years since Lyon’s paper about X inactivation, we assumed that the genetic machinery of a woman’s cell was not able to “open,” or access, the Barr body (remember, this is the silenced X). It turns out that Lyon wasn’t 100 percent right: the silenced X isn’t completely turned off. Rather, women have the use of two X chromosomes in every one of their trillions of cells—the silenced X is still helping the cell survive. About a quarter of the genes on the “silenced” X chromosome are in fact still active and accessible to female cells. We call this phenomenon “escape from X inactivation.”
As I’ll show in subsequent chapters, having another X chromosome provides extra genetic horsepower to each cell, which is an advantage that females have over males. The fact of the matter is this: If you are a woman and have inherited two X chromosomes in each of your cells, like the three and a half billion other genetic females on this planet, your cells have options. And when the going gets tough in life, those options help you survive.
Like each volume in the genomic encyclopedia set that I mentioned earlier, every chromosome provides genetic instructions from which we draw on every day of our lives. Need some more pancreatic lipase to help you break down the fat in that pistachio gelato you just ate? No problem. The cells in your pancreas will use the instructions from the PNLIP gene found on chromosome 10 to make some more. What about the lactose in that gelato? No problem again. Cells that line your gut can rely on instructions from the LCT gene that’s found within chromosome 2 to make all the lactase (the enzyme that breaks down lactose, the sugar in milk) you need to keep from feeling bloated.
So why is the X chromosome in particular so important in the game of life? Well, without it, human life isn’t possible. No one has ever been born without at least one X chromosome. Besides making life possible, it also provides us with a foundation from which we build and maintain a brain and from which we create our immune system. It’s a rich genetic volume of instructions that orchestrates the development and many crucial functions of the human body.
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HUMANS ARE NOT the only creatures on earth that use their chromosomes for sex determination. I first started working with honey bees over twenty years ago, and my research interests were initially sparked by a very simple question: What happens to a honey bee when it gets sick?
Honey bees have to collect pollen and nectar from numerous flower sources, often far away from their hives. And along this journey, they are exposed to all types of microbes.
Unlike vertebrate animals such as humans, honey bees don’t make antibody proteins to fight off an infection when they’ve been invaded by a microbe. Instead these insects have become quite adept at chemical warfare. Like a personal pharmacy on demand, honey bees are able to custom-make their own signature antibiotics to treat themselves when they have a microbial infection. (Some of these antibiotics, like apidaecin, can even sneak their way into the honey we consume.) The goal of my research with bees was to discover whether we could use the antibiotics that honey bees make to treat humans who have infections.
As a geneticist, I was fascinated by honey bee reproduction and genetics. Unlike many other animals, such as birds that use something akin to the XX and XY system, honey bees have a unique way of determining sex. I was reminded of this when I opened a hive one day and noticed the eggs the queen bee was actively laying in this hive—and she was a prodigious egg layer indeed. Queen bees lay eggs at a rate of about 1,500 per day.
Unlike Aristotle’s patrons who would do anything to have a say in the sex determination of their offspring, queen bees mastered the art of sex selection millions of years ago. The queen bee herself can make the royal decision of whether to lay an egg that will turn into a female worker bee or a male drone bee.
Here’s how it works: The queen lays an egg that has sixteen chromosomes, and if she does nothing more, it will develop into a male drone bee.* But if a queen wants to make a female worker bee, she adds a little dollop of sperm, which has been stored in her body, onto the egg. This sperm mixes with the egg and fertilizes it. The sperm that fertilized the egg adds another sixteen chromosomes for a total of thirty-two. That’s how many chromosomes it takes to make a female worker honey bee. While human females have an extra copy of an X chromosome, female honey bees have even more genetic options at their disposal. Every one of those sixteen extra chromosomes allows female honey bees to have more genetic choices than their male counterparts do.
Imagine that for a moment. Unlike human females, who have only one extra X chromosome compared with males, their honey bee compatriots have an entire extra set. Given all the duties entrusted to a female worker bee, it’s no wonder she has so much extra genetic material. For one, to ensure that the hive stays as germ free as possible, female honey bees spend an enormous amount of time and energy maintaining it. They also serve as guards, putting their lives at risk protecting the hive’s entrance if it’s threatened by predators.
Female honey bees are also entrusted to find all the nutritional sources the hive needs to survive. Then there’s the astonishing conversion of nectar into honey, which requires days of intensive effort. The first step to making honey is to add enzymes to digest the nectar. To aid the process, the female worker bees’ wings must buzz at a stroke rate of 11,400 times per minute. Their distinctive buzz is required to help dehydrate the liquid nectar, eventually turning it into honey. With all our scientific advances to date, humans have not yet found a way to successfully replicate this process.
A female honey bee can eventually progress from cleaning duty, to guard duty, to leaving the hive in search of pollen and nectar. It takes about two million visits to flowers, requiring an overall flying distance of fifty-five thousand miles, to make a single pound of honey. Not to mention that in the collection process, while they are avoiding predators, female honey bees also manage to pollinate 80 percent of the fruits, vegetables, and seed crops in the United States alone. If that isn’t enough, they also communicate to their fellow flying female workers through an elaborate dance, which lets them know where to find a good food source. Female honey bees have also been discovered to be the advanced mathematicians of the insect world. Australian and French researchers taught female bees how to do arithmetic operations such as addition and subtraction. This ability was thought to be out of reach for any insect, as it requires the capacity to perform complex cognitive processes. But not for a female honey bee.