The research promises to open new perspectives on the molecular basis of hearing and its alterations.

A team of Chilean scientists, led by Dr. Raúl Araya of the Centro Ciencia & Vida of the Universidad San Sebastián, has taken a crucial step in understanding mammalian hearing. Using advanced tools such as AlphaFold and molecular dynamics simulations, the researchers analyze the evolution of prestin, an essential protein in the inner ear that acts as a sound amplifier. “I am trying to understand how it works using these computational tools,” the specialist explains. These studies not only highlight the uniqueness of prestin in mammals, but could also open doors to understanding the molecular basis of the auditory process and its alterations.

  

From his laboratory at the Centro's facilities in Huechuraba, Dr. Araya Secchi uses computational biophysics tools to unravel the secrets of this unique protein, essential for sound amplification in the inner ear of mammals. “It is a protein with an unusual motor function that allows inner ear cells to change size in response to certain frequencies. This amplifies specific sounds, allowing us to hear everything from a pin drop to thunder,” the researcher explains.

Prestin was not always what it is today. Originally, it served a chloride transport function in non-mammalian organisms (fish, reptiles, birds). However, over millions of years, it evolved into a specialized molecular motor in mammals. This radical change occurred in two key stages: first, when they diverged from reptiles; and then, when placental mammals (such as humans) separated from marsupials and monotremes. “Those are the two major turning points we see in our analysis,” he details.

To explore this phenomenon, Dr. Araya Secchi and his team, in collaboration with Dr. Víctor Castro of the Universidad de Chile, employ a series of computational tools, among which AlphaFold stands out. This is an artificial intelligence system developed by DeepMind, owned by Google, which predicts how proteins adopt their three-dimensional structures from their amino acid sequences. This breakthrough has revolutionized biology, as knowing the shape of a protein is key to understanding its function and developing medical treatments.

Artificial Intelligence

AlphaFold uses deep neural networks and has demonstrated a level of accuracy that rivals traditional experimental techniques, allowing scientists to explore protein structures more quickly and efficiently. “We are reconstructing hypothetical models of what this protein might have been like in its ancestors. This allows us to trace evolutionary changes in its sequence, structure, and function,” he comments.

In collaboration with researchers from Valparaíso, they are also “resurrecting” these ancestral proteins in the laboratory, recreating them from DNA fragments and studying their properties. These measurements will allow them to validate computational predictions and deepen the understanding of their evolution. 

Prestin is an essential component in cochlear amplification, a phenomenon that gives mammals exceptionally sensitive and precise hearing. “Thanks to this protein, mammals have a wide auditory range and the ability to detect soft sounds that other species cannot perceive,” Araya explains.

“Mammalian hearing has high frequency selectivity, so we can set a very wide range and also of amplitudes. A person can hear a pin drop and also thunder, and this is partly achieved by this phenomenon of cochlear amplification. This means there are specialized cells in the cochlea that amplify certain sound frequencies, and to do so, they change size in response to the same frequency vibrating in the inner ear,” he details.

“Thus, the motor function of this protein changes its appearance, the area it occupies in the cell membrane. It is not like a channel that transports something and opens or closes. Rather, it changes from a compact to an expanded conformation in response to changes in membrane potential,” he maintains.

However, this capability is not without controversy. Some studies suggest that similar mechanisms might be present in birds, but current data indicate that the motor function of prestin is exclusive to mammals. “There are some researchers who say that a cochlear amplifier exists in non-mammalian animals, but the debate is whether that amplifier is prestin or another mechanism.”

Adaptation and Frequencies

Mammals had to adapt to hearing this higher frequency range to avoid being preyed upon by other larger predators. If we did not have this property, we probably would not be able to hear low-volume sounds and we would not be able to amplify sounds of those characteristics, says the specialist. “We would not be deaf, but we would perceive a lesser richness of sounds than we do today.” In fact, he comments that there are mutations in prestin that can lead to hereditary partial deafness.

Dr. Araya's work lies at the intersection of molecular biology, evolution, and cutting-edge technology. Although the study of prestin is a niche field, the researcher highlights its scientific relevance and the use of innovative tools that have gained global recognition, such as the Nobel Prize awarded to AlphaFold in 2024.

With plans to publish his findings in 2025, Dr. Araya not only seeks to unravel the mysteries of this protein but also to position Latin American science on the global map. “It is an area with few competitors, but with great potential to generate unique and relevant knowledge,” he concludes.

The research on prestin not only expands our understanding of auditory biology but also highlights how science can connect evolutionary history with the technology of the future.

Text by Richard García. SYM Comunicaciones.