Ancient fish genes found active in human ear development

LOS ANGELES — Scientists have made a groundbreaking discovery about the origins of the human outer ear, revealing that this distinctive mammalian feature evolved from an unexpected source: fish gills. This fascinating finding demonstrates how nature often repurposes existing genetic blueprints to create new structures throughout evolution.

Modern humans possess three distinct ear regions: the outer ear (including the visible portion and ear canal), middle ear (containing tiny bones that transmit sound), and inner ear (where sound waves are converted to neural signals). While scientists have long understood how middle ear bones evolved from ancient fish jaw bones, the evolutionary origin of the outer ear remained mysterious.

Cracking the black box of outer ear evolution

“When we started the project, the evolutionary origin of the outer ear was a complete black box,” said corresponding author Gage Crump, professor of stem cell biology and regenerative medicine at the Keck School of Medicine of USC, in a statement. The research team was inspired by Stephen Jay Gould’s famous essay “An earful of jaw,” which explained how fish jawbones transformed into mammalian middle ear bones.

Part of what made tracking the outer ear’s origins so challenging was its composition. Unlike bones, which can fossilize and provide clear evidence of evolutionary changes, the outer ear consists primarily of elastic cartilage – a flexible, specialized tissue that rarely preserves in the fossil record. This left researchers without direct physical evidence of how the outer ear emerged.

The first major breakthrough came when the team discovered that both gills and outer ears contain elastic cartilage, a relatively rare tissue type. “When we started the study, there was very little out there about whether elastic cartilage existed outside of mammals,” said Crump. “So it wasn’t really known if fish had elastic cartilage or not. It turns out that they do.”

The study’s first author Mathi Thiruppathy, a PhD student in the Crump lab, focused on gene control elements called enhancers. While genes often participate in developing many unrelated tissues and organs, enhancers tend to be much more tissue-specific. This specificity made them ideal for tracing evolutionary relationships.

Instead of relying on fossils, study authors turned to genetics and cellular analysis. The scientists successfully incorporated enhancers that help form the elastic cartilage of the human outer ear into zebrafish genomes. Remarkably, these human outer ear enhancers were active specifically in the gills of these transgenic zebrafish. The experiment also worked in reverse: when they created transgenic mice with zebrafish gill enhancers, these genetic elements became active in mouse outer ears.

Elastic cartilage prevails

Researchers also tracked how these structures evolved across different species. When they introduced either human ear or fish gill enhancers into tadpole genomes, these genetic elements became active in tadpole gills. In reptiles, the elastic cartilage of gills relocated to the ear canal, as demonstrated through experiments with green anole lizards. This cartilage eventually developed into the prominent outer ears characteristic of early mammals.

Perhaps most remarkably, the team found that even horseshoe crabs, ancient marine arthropods that diverged from our evolutionary lineage over 500 million years ago, use similar genetic programs in their book gills. The researchers performed DNA sequencing on individual cells of the horseshoe crab gills and discovered a crab enhancer that, when placed in the genome of zebrafish, had gill activity. This suggests that the very first elastic cartilage, similar to what is in our outer ears, may have first arisen in ancient marine invertebrates.

“This work provides a new chapter to the evolution of the mammalian ear,” said Crump. “While the middle ear arose from fish jawbones, the outer ear arose from cartilaginous gills. By comparing how the same gene control elements can drive development of gills and outer ears, the scientists introduce a new method of revealing how structures can dramatically change during evolution to perform new and unexpected functions.”

This evolutionary study, published in Nature, demonstrates how complex structures can arise through the modification of existing developmental programs rather than evolving entirely new ones.