The Basics of Genetics: How Women and Calico Cats are Similar

Hi PassioInventa readers! My first article will be an introduction to an awesome area of science I am pursuing in graduate school. Before you continue reading, try and think of what women and calico cats have in common. Calico, when talking about animals, refers to a coat pattern that is multicolored.

Photo credit: Andrea Tummons

Photo credit: Andrea Tummons

One of the most beautiful characteristics of animals is their diverse colors and patterns. They can be works of art, and sometimes shapes can be seen, like a cat whose fur pattern looks like it has a moustache. In the case of pets, we know that certain breeds of cats and dogs tend to have unique eye colors or coat patterns. Huskies have beautiful blue eyes and Siamese cats have white bodies with dark paws, tails, and ears. Calico cats are especially unique in their distinct coat pattern, and that usually only female cats are calico. Why is it that calico cats are almost exclusively female? And how does this relate to woman? To answer these questions, we need to go back to one of the most fundamental concepts of biology: DNA.

Fun fact: DNA, when stretched out, is about 6 feet long. How does a structure that big fit into a space smaller than a microscopic cell? Our DNA is compacted into a structure that kind of looks like a ball of yarn. This compacted structure is called a chromosome and is compacted so much, that it can fit inside a microscopic cell. DNA can be broken up into different number of chromosomes - humans have 23 chromosomes. Different species have different number of chromosomes, from plants to insects to mammals. Chromosomes also determine the biological sex of an organism. One pair of chromosomes is called the sex chromosomes. Males have an X and Y sex chromosome, and females have two X chromosomes.

Since females have two X chromosomes and males have one, this means that the females have two times as much X chromosome DNA as males do. Because of the imbalance, females have evolved a biological mechanism to shut off one of their X chromosomes, and make the levels of X chromosome DNA between males and females equal. This biological phenomenon is called X chromosome inactivation (XCI), and happens to essentially all female mammals. This is what women and calico cats have in common: An essential, fundamental biological process!

But what about calico cat spots? Let’s quickly discuss how DNA makes us, and these calico cats, unique. Our DNA is broken up into different sections called genes. Genes are responsible for creating all of the different parts that make us, us. Our height, hair color, eye color, what we can taste, etc. All of these genes have different versions. These versions can account for the differences in hair color, eye color, etc. In calico cats, there is a gene that determines what their coat color will be - brown or black. This gene is located on the X chromosome and since females have two x chromosomes, they will have two versions of the coat color gene. They can either have two black versions, two brown versions, or a black and a brown version (the black and brown are necessary to make a calico cat). As I mentioned above, the X chromosome is shut down to equalize X chromosome DNA between males and females. However, this X chromosome inactivation happens randomly in the beginning of development (during the blastocyst stage, shown in the image below), meaning some cells will shut off the chromosome with the black allele, and some will shut off the chromosome with the brown allele. When cells divide, they make two new cells that are exactly the same as the previous one. That means all the cells that come from the cell with the black allele shut off will become brown, and vice versa. The X chromosome randomly gets shut off early in development, during the blastocyst stage (image below).

X chromosome inactivation happens during the Blastocyst stage, when the developing organism is only ~70-100 cells. Organisms continue to develop into billions of cells.

X chromosome inactivation happens during the Blastocyst stage, when the developing organism is only ~70-100 cells. Organisms continue to develop into billions of cells.

How is this chromosome shut off? It is not as simple as flipping a switch, but it is carefully regulated system, that is so complex, we don’t even know all of the steps! The central dogma of biology paints the picture that DNA is a series of instructions (genes) for making different proteins (products of genes), the structural and functional units in our body.

DNA becomes RNA through a process called  transcription , and RNA becomes protein through a process called  translation.

DNA becomes RNA through a process called transcription, and RNA becomes protein through a process called translation.

However, to get from DNA to protein, there is an intermediate step in which the DNA is turned into RNA before becoming protein (Photo above). For a while it was thought that RNA only served this intermediate step, but new discoveries have revealed that RNA plays much more important roles than simply being an intermediate molecule. This makes sense since RNA was thought to be the original molecule that brought about life on Earth. RNAs can interact with protein, directing their function, and RNAs can also make 2D and 3D structures to work in the cell. In fact, it is thought that RNA may have a larger role in biological processes than we previously thought, and maybe even more than protein.

There is a large class of RNAs known as non-coding RNAs (RNAs that don’t get turned into protein). Of these, there is an RNA called Xist which stands for X inactive specific transcript. Xist is the non-coding RNA in mammals with placentas that is required for shutting off on of the two X chromosomes, and does so by interacting with proteins and bringing them to the X chromosome. This process is still unclear, and is something I aim to understand in graduate school!