For almost 100 years, children have been taught in school that the anatomical sex of a baby is determined by the X and Y chromosomes, also known as the sex chromosomes — XY is male and XX is female.
While this explanation fits the chromosomal makeup of most people, it leaves out “some exceptional human individuals who had not been understood previously,” said Dr. David Page, a biologist at the Massachusetts Institute of Technology, in an interview with Radiolab.
For example, some women who are physically female, including ovaries, have an X and a Y chromosome. And there are men, testes and all, who have two X chromosomes.
Page and other scientists, who were working on a precursor of the human genome project in the late 1970s, suspected that there was more involved here than just chromosomes. But before we get to that, let’s look at what people thought about the origins of sex before X and Y were discovered.
From Sex Chromosomes to Sex Genes
In the late 1800s, genetics was in its infancy. This was the time of Gregor Mendel and his genetic work with peas. He showed that certain traits of peas were passed from “parents” to “child” based on three principles of inheritance.
This carried over to how scientists thought about the passing on of traits in people. Some traits, like eye color, are inherited in ways that Mendel found with the peas. But even before Mendel, most people knew that children looked something like their parents, a kind of blending of the mother and father.
But anatomic sex was another matter altogether. There was no blending. “You ended up being either like your mother or your father,” Page told Radiolab.
Scientists thought this meant that sex was something different from heredity, something imposed from the outside. Maybe it was related to what the mothers ate when they conceived or their stress levels at the time.
The discovery of the sex chromosomes in 1921 changed the story we told about the origin of sex. This story held on until the late 1970s, when Page and other scientists found that a few of the anatomic XY females were missing a small part of the Y chromosome. And the XX males had an extra piece, the same part that was missing from the chromosome of the XY females.
Some part of the Y chromosome, not the whole chromosome, determined whether an embryo turned out to be male or female. In 1990, Professor Andrew Sinclair and his team identified this factor, a gene called the Sex determining Region Y gene, or SRY.
Of the about 200 genes on the Y chromosome, only this one is a “grand master switch” that determines the anatomical sex of a child. The protein made from the gene acts as a transcription factor — it attaches to specific regions of DNA and helps control the activity of the genes in those sections.
When SRY is activated in the embryo, it starts a cascade of gene activity that leads to the development of testes and eventually the other male sex characteristics. But the activation of SRY also plays another important role — it prevents the development of ovaries and female reproductive structures such as the uterus and fallopian tubes.
SRY is only active for about a day, but other genes in the cascade remain active. One of these is called DMRT1.
In 2011, David Zarkower, a genetic cell biologist at the University of Minnesota, and his team discovered that if they used genetic editing to remove the DMRT1 gene from male mice, cells in the testis would become like female ovary cells. This happens even when the editing is done in adult mice.
There’s another gene, called Foxl2, that plays a similar role in ovaries — if you remove it from female mice, the ovary cells become more like male testis cells.
For a long time, scientists thought that once the embryo started on the path toward becoming male or female, the decision was final. But Zarkower’s and other scientists’ work shows that the gonads have to maintain the original sex determination over the entire course of the animal’s — or person’s — life.
Sex Is More Flexible in Some Species
In people and in mice, this genetic path toward male or female is permanent, unless a geneticist comes along and removes the DMRT1 or Foxl2 genes. But in bluehead wrasse, a fish that lives around the coral reefs in the Florida Keys, it’s another story.
Bluehead wrasse live in groups of many females and one male. The male mates with all the females in the group. If the male dies, the females will no longer be able to produce offspring.
But the species has a “trick” to keep the community going. Shortly after the male dies, one of the other females starts acting differently toward the other females — basically, this female behaves more like a male bluehead wrasse.
She then undergoes physical changes — she grows larger and her color patterning shifts to look more like a male. Inside, her ovaries disintegrate and rebuild themselves into testes that start producing sperm. When it’s all done, she can fertilize the female’s eggs — she’s now the male of the group.
Bluehead wrasse are not the only species with this ability. This kind of sex change occurs in other fish, shrimps, worms, alligators, flies, lobsters, chickens, eels and turtles. Scientists think this ability increases the genetic fitness of an individual, because it can have offspring as both the receiver and the maker of sperm.
This type of sex switch couldn’t occur in people, though, because our bodies undergo so many physical — and irreversible — changes throughout development. At the most, you might be able to produce different sex hormones in your testes or ovaries.
For some scientists, moving beyond the sex-chromosome model of anatomic sex opens up a new understanding of the human species.
“There’s a tremendous amount of middle ground, even when you’re just talking about the level of testosterone you’re making, or the level of estrogen you’re making, or the shape of your genitalia,” Blanche Capel, a geneticist at Duke University, told Radiolab.
The genetic basis of anatomic sex as we now know it also suggests something even more amazing. When we were just starting out as embryos, we stepped onto a path toward becoming male or female. While genetically we can’t turn back, we still have that “other path” somewhere deep inside us — our sexual alter ego, held back by a single gene.
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