X Marks The Genetic Mystery

In today’s New York Times, I have a feature about the X chromosome. The X chromosome is one of those things that we learn about early on in school, and yet it still contains mysteries–ones that potentially have a direct impact on our health. Men have one X chromosome and one Y, while women have two X’s. This imbalance has led to all sorts of remarkable things–most remarkable of which is the fact that women shut down one of their X chromosomes–but which chromosome (mom or dad’s) depends on the cell.

I explore several lines of research in this piece, but the original nudge came from one new study in particular. Jeremy Nathans of Johns Hopkins and his colleagues came up with a way to light up cells based on which X chromosome they used. The complexity is gorgeous.

Here are three images that we didn’t have room for in the news article. Red cells use the father’s X, green cells the mother’s. Bear in mind that each chromosome carries different versions of the 1,000+ genes on the X. What these patterns mean for female biology is anyone’s guess.

First, an auditory hair cell from the inner ear of a mouse:

Jeremy Nathans and Hao Wu/Neuron
Jeremy Nathans and Hao Wu/Neuron

Then the tongue in cross-section (note the side-to-side differences):

Jeremy Nathans and Hao Wu/Neuron
Jeremy Nathans and Hao Wu/Neuron

And, finally, the heart:

Jeremy Nathans and Hao Wu/Neuron
Jeremy Nathans and Hao Wu/Neuron

8 thoughts on “X Marks The Genetic Mystery

  1. One possible explanation of the extreme susceptibility of human females to autoimmune disease has been that they fail, partially or completely, to inactivate one X-chromosome, so that the concentration of X-chromosome gene products is increased in females, and this makes them susceptible to attack by their own lymphocytes. Scanning the beautiful pictures of Nathans and colleagues, one seldom comes across a cell of intermediate color (not pure red or pure green). And those that are seen are explained as due to the super-imposition of two cells. It would be of great interest to apply this fascinating new technology to organisms where the sex that dosage compensates is prone to autoimmune disease.

  2. I guess the x chromosome will be a puzzle for quite some time, as it contains the majority of our biological soup. Why the y chromosome alters so little over time, and is essentially the same y as the first man (with only a few mutational markers along the way) is also a mystery. Life began (the original blueprint) through female mitosis and cell division resulted in clone daughter cells, with the only diversification being when a cell mutated, creating a slightly different cell and organism. Add the mutated y to the equation, and we see further genetic diversity, the making of male, the beginning of sexual reproduction and the end of cloning; although the y chromosome is a form of cloning in males where mutations occur rarely. Thank goodness boys and men have an x chromosome! As, the y has altered so little over time and is so small, and the x contains many combinations of x’s from both paternal and maternal lines and is so huge, and changes with each generation, it is no wonder that some form of x truncation(inactivation) occurs, in order to synthesise with the smaller and less adaptable y. Well, that is what makes sense to me.

  3. Hi Carl,

    I am not sure whether you are aware of a great book (A History of Genetics) written by the great geneticist A. H. Sturtevant (T H Morgan’s student). http://www.esp.org/books/sturt/history/

    Here is an excerpt from page 49 where Sturtevant explains the etymology of “X chromosome”. The whole book is a great read!

    Best regards,

    “The first suggestion of the relation of a particular character to a particular chromosome was made in 1901, when McClung postulated that the so-called accessory chromosome (now known as the “X chromosome”) is male determining. This body was first described by Henking (1891) in the male of the bug Pyrrhocoris.”

    “For a long time it was considered doubtful that it was a chromosome, and its uncertain nature and function were the reason for giving it the designation “X.” Henking showed that it divides at only one of the meiotic divisions, with the result that it is present in two of the four sperm arising from each primary spermatocyte and absent in the other two. Other investigators (especially Montgomery) confirmed this description for other Hemiptera, and McClung and Sutton found the same relations in several grasshoppers. Sutton, at McClung’s suggestion, studied the female; unfortunately the material was difficult and the chromosome number was large, with the result that he counted 22 in the female as compared to the 23 clearly present in the male. Therefore the X was interpreted by McClung as producing maleness, and the supposed significance of the two kinds of sperm was the reverse of the true one.”

    “The correct relation was shown in 1905 for a beetle (Tenebrio) by Stevens; in this case there was also a Y present, smaller than the X, and she showed clearly that the female is XX, the male XY. This result was immediately confirmed by Wilson (also in 1905) for Hemiptera and was soon shown for Orthoptera, Diptera, Homoptera, Myriapoda, and, with less certainty, for various other kinds of animals.”

    “These relations were sometimes interpreted on the basis that the sex chromosomes were not the cause of the differences between males and females, but were merely a kind of secondary sexual character, resulting from some other more basic sex-determining mechanism.”

  4. Hi again Carl

    One final point that I feel requires emphasis:

    Barr Bodies aka “inactivated X chromosomes” are not completely inactive. This must be true since neither Kleinfelter males nor Turner females are completely “normal”, even though XXX females are “normal”.

    (tip to high school teachers: refrain from searching “XXX females” on school web browsers. It can be difficult to explain such inadvertant and innocent misunderstandings to administrators.)

    The best I can understand is that the phenotype in Turner’s syndrome is not due to loss of the entire X chromosome but rather to haploid dosage of a gene or genes; i.e. haploinsufficiency. Of course, that is only possible if the Barr body has residual genetic activity.

    best regards,

  5. Loved the article in the Science Times and thought the photos were fascinating. I realize that the “how” of the shutting down of one of the Xs is still being studied but I also wondered about the “when”. Are they all shut down at once? Does this happen in utero? Later? I think this has some interesting, if subtle ethical implications.

  6. It’s really a fascinating article. Actually in real life as a mother, sister and daughter, I noticed that every one of every individual is a mosaic mixture of our parents including mental charecters. For my pleasure these pictures confirm the reality of real life, that we are not more than biological robots; consisting of cells that primerily desighned by the genetics of our ancestors. Untill these days; scientists deny these simple but so clear facts, and I hope that these methods will soon illustrate that we are a random mixture of genetic material; that determine who we will be. It’s a pure biological determinism; we should not be so afraid to accept this fact. Determinism is not a desaster; but a fact that we have to live with peacefully.

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