Scientists deepen understanding of X chromosome’s role

Study examines rich complexity of the gene carrier

NEW YORK — The term “X chromosome” has an air of mystery to it, and rightly so. It got its name in 1891 from a baffled biologist named Hermann Henking.

To investigate the nature of chromosomes, Henking examined cells under a simple microscope. All the chromosomes in the cells came in pairs.

All except one. Henking labeled this outlier the “X element.” No one knows what he meant by the letter. Maybe he saw it as an extra chromosome. Or perhaps he thought it was an ex-chromosome.


Today, scientists know the X chromosome much better. It helps determines whether we become male or female. If an egg inherits an X chromosome from both parents, it becomes female. If it gets an X from its mother and a Y from its father, it becomes male.

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But the X chromosome remains mysterious. For one thing, females shut down an X chromosome in every cell, leaving only one active. That is a drastic step to take, given that the X chromosome has more than 1,000 genes.

In some cells, the father’s goes dormant, and in others, the mother’s does. Although scientists have known about this so-called X-chromosome inactivation for more than five decades, they still know little about the rules it follows, or even how it evolved.

In the journal Neuron, a team of scientists recently unveiled an unprecedented view of X-chromosome inactivation in the body. They found a remarkable complexity to the pattern in which the chromosomes were switched on and off.

At the same time, each copy of the X chromosome contains versions of genes not found on its partner. So having two X chromosomes gives females more genetic diversity than males, with their single X chromosome. Because of that, females have a genetic complexity that scientists are only starting to understand. “Females simply have access to realms of biology that males do not have,” said Huntington F. Willard, the director of Duke University’s Institute for Genome Sciences & Policy, who was not involved in the research.


But although the additional genes provided by their second X chromosome may in some cases provide females with a genetic advantage, X chromosomes also have a dark side.

Their peculiar biology can lead to genetic disorders in males and, new research suggests, create a special risk of cancer in females. Understanding X-chromosome inactivation can also shed light on the use of stem cells in therapies.

A Japanese biologist, Susumu Ohno, first recognized X-chromosome inactivation in the late 1950s. In every female cell that he and his colleagues studied, they found that one of the two X chromosomes had shriveled into a dormant clump. Scientists would later find that almost no proteins were being produced from the clump, indicating that it had been shut down.

British geneticist Mary F. Lyon realized that she could learn more about X-chromosome inactivation by breeding mice, because some color genes sit on the X. In 1961 she reported that female mice sported patches of hair with their mother’s color and others with their father’s.

Getting a deeper look at how females shut down their X chromosomes has remained a challenge.


In recent years, Dr. Jeremy Nathans, a Howard Hughes Medical Institute investigator at Johns Hopkins University, and colleagues have developed a way to make X chromosomes from different parents light up. They inserted a set of genes into the X chromosomes of mice.

The genes produced a green fluorescent protein, but only if their X chromosome was active and they were exposed to a particular chemical trigger.