In Response To: "Insects, Sex, and Selection"

By: Christopher

In response to Insects, Sex, and Evolution, I would like to weigh in on the offhand statement that Chris put forth:

"Do conclusions drawn from the laboratory coincide with those drawn from the field (assuming that the field provides a more accurate depiction of reality)?"

To assume that the field provides a more accurate depiction of reality than the laboratory is a common pitfall that many scientists fall in to. The often unspoken assumption seems logical; however, it can lead to decades of setbacks in the scientific community if haphazardly assumed. The progression of X chromosome research perfectly exemplifies this point.

Human males have a single X chromosome, while females have two X chromosomes. To compensate for having an extra X chromosome, females essentially silence one of their X chromosomes early in development, leaving them with a single functioning X chromosome analogous to males. This process, entitled "X chromosome inactivation," is essential for the survival of females; if neither or both X chromosomes are mistakenly silenced in a female cell, the cell will die.

When looking at females in "the field" (females that go to the doctor to get checked out), an astonishing fact is realized: all females have a single activated X chromosome. This means that for females with a disease where they have only a single X chromosome, their single X chromosome does not get silenced. This also means that females with a disease where they have three X chromosomes, two of their X chromosomes are silenced leaving a single active X chromosome. The most astonishing cases in "the field" are females with 4, 5, or 6 X chromosomes: no matter how many X chromosomes a female in "the field" has, she will always silence all of them but one.

If you make the false assumption that what you observe in "the field" is an accurate depiction of reality, then the logical question follows: How do cells count X chromosomes? Clearly, cells must be able to know how many X chromosomes they have before they can silence all but one of them. A cell must be able to know that it has 5 X chromosomes before it can silence 4 of them. So how do cells count chromosomes?

This question has been repeatedly asked for the last twenty years, but has remained unanswered. It is an impossible question to answer, because it relies on the false assumption that "the field" is an accurate depiction of reality.

In this case, "the field" is a skewed depiction of reality; "the field" showed that cells inactivate all of their X chromosomes except for one. What scientists have neglected to realize for the last twenty years is that "the field" is only composed of individuals and cells that have survived. What scientists are now beginning to realize is that the cell likely does not have a mechanism for counting X chromosomes. Instead, in a developing female, cells with more than two X chromosomes will start silencing chromosomes at random. If, for instance, the female has 5 X chromosomes, some cells in the developing female will silence 5, while some will silence 4, 3, 2, 1, or none. Only the cells that end up silencing 4 X chromosomes will survive, and the female will develop from those properly silenced cells.

Additionally, scientists are beginning to realize that most developing females with an abnormal number of X chromosomes die before being born. Only the females that were lucky enough to randomly have the right number of X chromosomes silenced in the majority of their cells survive.

The important conclusion to be drawn from this lengthy explanation of how X chromosome inactivation works is that scientists assumed that cells must have some way to count their chromosomes because all of their "field" observations led them to this logical question. "The field", in this case, was greatly skewed though, because it only took into account living individuals and living cells. To correct for this hindrance, scientists have moved to studying X chromosome inactivation in a synthetic laboratory setting, rather than in "the field" from human samples.