Gene Plays a Critical Role in the Gender Divide
JACKI LYDEN, host:
If there's one fact about genetics that everybody knows, it's that females have two X chromosomes and males have an X and a Y. But facts sometimes get a little squishy. As it turns out, there are people in the world, possibly more than you imagine, who have a Y chromosome and look entirely female, and there are people who have two X's who look entirely male. Now, scientists in Italy are reporting they found a new gene that appears to play a critical role in deciding which sex you look. NPR's Joe Palca has more.
JOE PALCA: For several years now, Orietta Radi and her colleges at the University of Pavia have studied an unusual family, unusual because in the family there are four brothers who have two X chromosomes.
Ms. ORIETTA RADI (University of Pavia): XX males are quite rare. One out of 20,000 in population.
PALCA: Radi says if you were to bump into one of these men, you'd have no idea they were missing the Y chromosome that typically makes men men.
Ms. RADI: Usually they look like a normal male, but they have often some problems in external genital development.
PALCA: Radi says surgery is frequently needed to make things work properly. Because these men were from a single family, it made sense to search for an inherited gene that might be causing the sex reversal. And sure enough, they found one: a gene called R-spondin. The XX brothers in the family had inherited a disabled copy of R-spondin. Radi and her colleagues report their work in the online edition of the journal Nature Genetics.
To understand how a single gene like R-spondin can determine maleness or femaleness, you have to understand a little bit about how our reproductive organs come into being. About six weeks after conception, the structure that will someday become testes or ovaries appears. Now, at six weeks that structure is exactly the same in males and females. This is a time of decision, or as geneticists Robin Lovell-Badge puts it...
Mr. ROBIN LOVELL-BADGE (National Institute for Medical Research): A delicately poised situation which could go either way.
PALCA: Lovell-Badge is at the National Institute for Medical Research in London, where he studies the genetics of sex determination. He says typically if there's a Y chromosome around, it has a gene that will nudge things along in the male direction. Testes form. They start producing male hormones, and those hormones cause things to become male-like.
What the new research shows is that the same thing can happen even if the Y chromosome isn't around, if the R-spondin gene is damaged or missing. Now, XX males with a missing R-spondin look like males, but without the Y chromosome they won't be fertile.
Mr. LOVELL-BADGE: There are genes on the Y chromosome which you need to make functional sperm, so it's entirely predictable that XX males will be sterile, and you can't get around that.
PALCA: In addition to not being able to make sperm, there are some other male traits you miss out on if you're a male without a Y.
Mr. LOVELL-BADGE: To give you a simple example, there's a gene on the Y - human Y chromosome that's responsible for making a particular protein that coats the enamel of teeth. So in fact, human men have different teeth slightly from women. So these XX males will actually have the female pattern in their teeth, rather than the male pattern.
PALCA: I presume those are subtle differences.
Mr. LOVELL-BADGE: They are very subtle, yeah.
PALCA: The Italian team's discovery of R-spondin is probably not the final word in the genetics of sex determination. Eva Eicher works in that field at the Jackson Laboratory in Bar Harbor, Maine. Eicher says not only are there genes that can turn someone with two X chromosomes into a male...
Ms. EVA EICHER (Jackson Laboratory): We've been narrowing in on a gene that does the opposite. We get XY females. We get XY individuals with ovaries.
PALCA: It's important to point out that Eicher has only found this effect in mice, not humans.
Ms. EICHER: But so far we have found that genes that affect the gonadal development in humans, that the same genes are key players in the mouse too.
PALCA: Adding a new twist on that old question, are you a man or a mouse? Joe Palca, NPR News, Washington.
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