Scientists have discovered that the genetic program responsible for the formation of fingers in terrestrial animals may have originated from an unexpected source—non-coding regions of the genome.

Evolution of Limbs: From Fish to Land Animals

Millions of years ago, the ancestors of modern vertebrates began to adapt to life on land, evolving from fish into a variety of species with feet, hands, and fingers. How exactly these limbs appeared remains one of the oldest questions in biology.

There is a hypothesis that the fingers of land animals and the fins of fish share a common evolutionary origin and may have developed through a single genetic program. However, the details of this process are still the subject of scientific debate.

An Unexpected Genetic Mechanism

An international team of researchers has found that the formation of fingers during evolution involved an ancient segment of the genome, which was originally responsible not for fin development, but for the formation of the cloaca—an organ that combines the exits of the digestive, excretory, and reproductive systems in many species. The results of the study were published in the journal Nature.

Biologists studied not only the genes directly involved in finger development, but also extensive non-coding DNA regions that regulate gene expression and activation. These regions are called "regulatory landscapes"—they are much larger than the coding regions, which make up only about 2% of the genome. Non-coding regions can be compared to control centers that manage the activity of genes.

Experiments with Mouse and Fish Genomes

During the study, scientists worked with the genomes of mice and zebrafish. First, they identified a regulatory landscape common to both species that is involved in finger development in mice. Then, using CRISPR/Cas9 technology, biologists deleted this large DNA segment in fish and observed the development of their embryos.

Deleting this segment led to a loss of gene expression in the cloaca region, but not in the fins. This showed that the regulatory element was originally linked to cloaca development, and during evolution in terrestrial vertebrates, it was "repurposed" for finger formation.

Common Features of the Cloaca and Fingers

As study author Aurélie Hintermann explains, the cloaca and fingers share the characteristic of being terminal structures—that is, they are located at the ends of biological axes or systems. Sometimes this is the end of the digestive tract, sometimes the end of limbs, meaning the fingers. Thus, both the cloaca and fingers encode the "end" of a particular structure.

The Role of Hox Genes and Evolutionary Insights

The regulatory landscapes of interest to scientists control the activation of Hox genes—so-called "architect genes" that determine the position and identity of segments and organs, as well as direct the growth and specialization of tissues. These genes sit at the top of a complex network that regulates thousands of other genes, and their mutations can lead to significant anatomical changes. The function of Hox genes is crucial for evolution.

Professor Denis Duboule, the initiator of the study, notes: "The involvement of these genes in this process is a vivid example of how evolution creates something new by reworking the old. Instead of building a new regulatory system for fingers, nature repurposed an existing mechanism that was originally active in the cloaca."

New Horizons for Research

Based on the data obtained, scientists concluded that the architecture of regulatory and coding genes evolved first. Sometimes, an entire genetic region could be used in a new morphological context. Now, researchers are shifting their focus from where changes occur in the genome to how these changes are implemented.