It’s the Genes, Not the Chromosomes
It’s not the chromosomes themselves that determine your sex. It’s the genes inside them.
Chromosomes are the folded strands of DNA organized into structures. These structures match with their pair, one from each of your parents, and make up your genetics. We call this pair homologous. Homologous comes from the Greek root words homo meaning "same" and logos meaning "plan or reason". For this purpose, homologous means the same structure. Their structure is important for DNA replication to ensure that DNA is accurately copied and separated for new cells.
Each chromosome has a homologous pair, except for the 23rd pair of chromosomes. These are typically referred to as your "sex chromosomes".
Why?
In 1905, Nettie Stevens was looking for what caused sex development. She found that in mealworms there was a discrepancy in the size of what was considered to be an unimportant "accessory chromosome”. She discovered that during the creation of the mealworm's sperm, all the chromosomes divided evenly during replication except for one pair. This pair was divided into one small chromosome (Y) and one large chromosome (X). It was a discrepancy that was found only in sperm development, as the eggs in females contained two identical chromosomes. Through these studies, we have come to understand that in many species two large chromosomes (XX) result in females and one large and one small chromosome (XY) result in males.[1]
We still teach the concept that XX results in females and XY results in males. But is that what actually causes the differentiation into male or female? Remember, chromosomes are just folded, organized DNA. Is it the shape of the DNA that matters?
To understand, we need to look at a rare disorder of sex development (DSD): de la Chapelle syndrome. De la Chapelle syndrome is also known as XX male syndrome. I can already sense your confusion, as we just discussed that XX results in females. To understand how this condition is caused, we are going to first discuss the normal process of gamete creation (eggs and sperm).
All cells divide to create new cells in a process called mitosis. But only specific cells go through a process called meiosis. Meiosis is the process a cell goes through to divide up the pairs of DNA so that there is only a single copy of each chromosome in the new cells. Each DNA set is then formed into gametes, either eggs or sperm.
Occasionally, the homologous chromosomes in a pair will exchange equal parts of DNA prior to separating. This is referred to as a crossover event, a way to add diversity to the genetics that are passed onto future generations. But occasionally this will happen to non-homologous chromosomes (chromosomes that do not have the same structure, like X and Y). When this happens, we call it translocation.[2]
When a crossover event takes place, nothing significant is impacted because the exchange is of equal amounts of DNA that codes for the same traits. With translocation events, it is not the same DNA being exchanged. This results in many disorders ranging from a specific kind of Down Syndrome, leukemia, muscular dystrophy, and some types of cancer [3]. Translocation and crossover events are not supposed to happen for sex chromosomes.
This brings us back to de la Chapelle syndrome. De la Chapelle is a condition that results from a translocation event where DNA from the Y chromosome is exchanged for DNA from the X chromosome. Specifically, the SRY gene, the master switch sex determining gene for male development, translocates from the Y chromosome to the X chromosome. As a result, you will have a male offspring with XX chromosomes. Most individuals with de la Chapelle syndrome do not find out until they experience infertility. Their physical appearance is otherwise typical of a male.[4]
With sex and chromosomes, the entire issue comes down to this: Are chromosomes what determine your sex? Is it the shape of your DNA that determines your sex?
The answer is no. For the majority of the population, XX will result in female offspring and XY will result in male offspring. But it is not the shape of the DNA that determines sex. It is the genes encoded into the DNA that determine sex.
Below is the sex development path for XX male syndrome.
