Humans' outer ears may have evolved from the gills of prehistoric fish, according to a new study. Gene-editing experiments indicate that cartilage in fish gills migrated into the ear canal millions of years ago during our evolution. Researchers suggest that the evolutionary roots of outer ears may extend even further back to ancient marine invertebrates, such as horseshoe crabs.
The research provides insight into the origins of outer ears, which are unique to mammals. Gage Crump, a professor of stem cell biology and regenerative medicine at the University of Southern California and co-author of the study, remarked, "When we started the project, the evolutionary origin of the outer ear was a complete black box."
Previous findings established that our middle ears, located behind the eardrum and composed of three small bones, originated from the jawbones of ancient fish. This transformation of anatomical structures led researchers to wonder if the cartilaginous outer ear also derived from some ancestral fish structure.
Human outer ears, as well as those of other mammals, contain a subtype of cartilage known as elastic cartilage, which is more flexible than hyaline cartilage or fibrocartilage found in the human nose and vertebral disks, respectively.
A key discovery linking human outer ears to fish was the presence of elastic cartilage in fish gills. Crump stated, "When we started the study, there was very little out there about whether elastic cartilage existed outside of mammals."
Using protein stains, researchers found that the gills of zebrafish (Danio rerio), Atlantic salmon (Salmo salar), and three other fish species contain elastic cartilage. This indicates that elastic cartilage is a common feature among modern bony fishes, as reported in the study published on January 9 in the journal Nature.
The scientists further examined the evolutionary connection between elastic cartilage in fish gills and mammalian outer ears. Since elastic cartilage does not preserve well in fossils, they utilized molecular clues instead. They investigated gene control elements known as "enhancers," which are short DNA sequences that activate associated genes when bound by specific proteins.
Due to the highly tissue-specific nature of genetic enhancers, researchers easily detected their activity. To assess whether enhancer activity—and thus gene regulation—was similar in fish gills and human outer ears, Crump and colleagues inserted human outer ear enhancers into zebrafish genomes, triggering activity in the gills.
In a reverse experiment, they inserted enhancers from zebrafish gills into mouse genomes and observed activity in the mice's outer ears. Additional experiments with tadpoles and green anole lizards (Anolis carolinensis) demonstrated that amphibians and reptiles also inherited their gill and ear structures from fish. In lizards, enhancer activity was located in the ear canal, indicating that elastic cartilage began migrating from the gills to the outer ear around 315 million years ago when reptiles emerged.
The findings suggest that elements of an ancestral gill developmental program were reutilized multiple times throughout vertebrate evolution to produce diverse gill and ear structures. The team also identified an enhancer in horseshoe crab cells that activated zebrafish gills, indicating that our outer ears might have deeper evolutionary roots than previously recognized.
While further research is necessary to confirm the extent of these roots, Crump stated, "this work provides a new chapter to the evolution of the mammalian ear."