A mule is a hybrid animal resulting from the cross between a female horse and a male donkey, a combination that has been intentionally bred by humans for millennia. While mules inherit the strength of the horse and the endurance of the donkey, they possess a biological characteristic that prevents them from having offspring of their own. The vast majority of mules are sterile, a phenomenon whose underlying genetic mechanism is now well understood.
The Horse and Donkey Parents
The ability of any organism to reproduce successfully starts with the number of chromosomes, the structures within cells that contain an animal’s DNA. Horses and donkeys belong to the same taxonomic family but are separate species, a distinction reflected in their differing chromosome counts. A domestic horse possesses 64 chromosomes, meaning its body cells contain 32 pairs. The donkey, in contrast, has 62 chromosomes, consisting of 31 pairs.
When a horse and a donkey mate, each parent contributes exactly half of its chromosomes to the offspring through a reproductive cell. The horse contributes 32 chromosomes from its egg cell, and the donkey contributes 31 chromosomes from its sperm cell. The resulting mule inherits a total of 63 chromosomes in every body cell.
The Chromosomal Mismatch
Successful sexual reproduction relies on meiosis, a specialized process of cell division responsible for creating viable eggs or sperm. Meiosis requires that chromosomes pair up precisely with their homologous partners, meaning the two chromosomes in a pair must be similar in size and structure. In the mule, the 63 chromosomes inherited from two different species cannot find perfect matches to form the necessary 31 pairs.
The mule’s 63 chromosomes include 31 pairs where the horse and donkey chromosomes are structurally similar enough to align. However, one chromosome is left without a partner, and many of the other chromosomes differ significantly in structure and size due to evolutionary separation. This failure to align correctly during meiosis prevents the formation of proper chromosome pairs.
The disruption in pairing causes the subsequent division of the chromosomes to be highly irregular, leading to an unequal distribution of genetic material into the sex cells. These malformed gametes are non-viable and incapable of producing a new organism, which is the direct cause of the mule’s sterility. Male mules are sterile because their sperm production fails during this meiotic division.
The Phenomenon of Fertile Mules
While the biological mechanism of sterility is effective, there have been rare cases of female mules, known as “molly mules,” producing offspring. For a female mule to become pregnant, she must somehow manage to produce an egg with a viable, even number of chromosomes.
One possible explanation suggests that the mule’s reproductive cells selectively discard the donkey-derived chromosomes. This process would result in an egg containing only the 32 horse chromosomes. If this egg is then fertilized by a horse, the resulting foal would be genetically horse-like, possessing 64 chromosomes.
Another possibility is that the mule produces a viable egg containing only the 31 donkey chromosomes, which then results in a donkey-like foal when fertilized by a male donkey. These events are infrequent and are considered an occasional, imperfect bypass of the meiotic barrier.

