A Genetic Patchwork: The Story Behind Calico Cats and Sex Chromosomes
Written by and illustrated by the X-plainers, Devyn Deschamps and Jimin Lee
Around Duke University, kittens dash across campus so quickly that most people don't notice the patterns in their fur. But a cat’s coat can tell a much deeper story, revealing how genes influence visible traits during development.
Calico cats are known for their multicolored fur, featuring orange and black patterns that, at first glance, appear to be random. The patterns that appear on Calico cats are related to their sex chromosomes.
Sex chromosomes, the X and Y chromosomes, can determine female or male anatomy, but they also play much broader roles across the body. They carry genetic information that influences how cells function, shaping our bodies and health in ways that are not always easy to see. Calico cats offer a visual window into X chromosome biology, revealing how processes unique to the X chromosome influence coat color patterns.
Cats typically have 38 chromosomes, grouped into 19 pairs. Most pairs match, but one pair is different. Biological females typically have two X chromosomes (XX), whereas biological males usually have an X and a Y chromosome (XY).
Chromosomes contain genes, which are segments of DNA that give cells instructions, such as fur color. In cats, a fur-color gene is located on the X chromosome, but the Y chromosome does not carry this gene. Because male cats typically have only one X chromosome, they usually have fur that is completely black or orange, which is why calico-colored male cats are rare.
Female cats typically have two X chromosomes (XX). Early in development, each cell randomly inactivates one X chromosome to balance gene activity, since having a double dose of X chromosome genes can be problematic. The process of X-chromosome inactivation is essential for this balancing of gene activity. Once an X chromosome is inactivated in a cell, all cells that descend from it keep the same X chromosome turned off.
As a result, different cells in a female cat may use different X chromosomes. If both X chromosomes carry the same fur-color gene, which scientists call “homozygous”, the cat will be one color: orange or black.
If the X chromosomes have different fur-color genes, known as “heterozygous”, patches of cells express different colors, creating the mosaic pattern we recognize in calico cats.
The active X gene goes through the process of transcription to create RNA, which is translated into a protein that provides the coat’s color. The silenced gene is not transcribed into RNA, and it does not contribute to coat color.
Depending on which X chromosome is active, either orange or black fur will grow, linking coat color directly to patterns of gene expression.
But how does a cell shut off one of the X chromosomes? Early in development, in cells with two chromosomes, one of the X chromosomes randomly produces a RNA called XIST, which spreads across that same chromosome and triggers epigenetic changes, or modifications to the DNA that condense it, and reduce its ability to make proteins. These changes largely silence this “inactive X”, allowing the other X chromosome to produce all the RNAs and proteins needed by the cell.
X-chromosome inactivation occurs in individuals with two or more X chromosomes. Typically, this means females, who have two X chromosomes, undergo inactivation of one X, while males do not, since they usually have only one X and one Y chromosome.
On rare occasions, a male cat can have calico fur patterning if he has an extra X chromosome, which would mean he has XXY sex chromosomes. In these cases, X-chromosome inactivation still occurs, allowing different cells to express different X-linked coat color genes, much like in female calico cats. This condition is similar to Klinefelter syndrome in humans.
While humans don’t have fur like cats, we share the same chromosomal-level processes. People with two X chromosomes also undergo X-chromosome inactivation, creating a mosaic of cells that have different active X chromosomes.
Unlike in cats, however, X-chromosome inactivation in humans usually cannot be seen by the naked eye. A well-known example involves red-green color vision. The gene responsible for making proteins that detect red and green light is on the X chromosome. Males, who only have one X, will be red-green colorblind if that gene doesn’t work. Similarly, females with two nonfunctional copies of this gene can be colorblind.
In contrast, a female with one nonfunctional copy of the gene typically still sees red and green because she has a second, functional copy of the gene on her other X chromosome. Due to X-chromosome inactivation, females are mosaics: in some eye cells, the X chromosome carrying the functional gene is active, while in others the X with the nonfunctional gene is active. This creates a mosaic pattern of cells in the eye, similar to what is observed in calico cats’ fur coats.
A more straightforward way to think about it is that, in biological females with a nonfunctional color-detecting gene on the X chromosome, on average, half of the cells in the eye will be able to detect red and green light. As there are about 6 million cone cells that are responsible for detecting color, not bad odds!
At first glance, humans and cats may not seem to have much in common, but our biology connects us in fascinating ways.
The San Roman Lab is committed to pioneering discoveries that advance our understanding of the genetic and molecular basis of sex differences in human health.
One focus of the lab’s research is to understand how genes on the X chromosome shape cellular processes and contribute to sex differences in human health and disease.
While sometimes it may be hard to visualize these differences, after seeing a calico kitten run across campus, perhaps think twice about the complex genetic mosaicism that both you and that kitten may share.
This article is the first project in the X-plainers’ initiative, a team of Duke undergraduate students producing scientific communication within a R1 University. This project has been under the supervision of graduate student, Hannah Kubinski & Dr. Adrianna San Roman. To read more about X-plainers, click below.
