How Brand New Genes Are Born From DNA That Did Nothing

A discovery that upends the accepted idea of where genes come from

The classic dogma of genetic evolution

For a long time, evolutionary genetics rested on a simple and widely accepted idea: every gene in an organism descended from older genetic ancestors, passed down and gradually modified across generations through duplication, mutation, or rearrangement of sequences that were already functional. This view, long considered a pillar of molecular biology, explained genetic diversity as the product of gradual variation from pre-existing genetic material.

Did you know that a team at Rockefeller University recently shed light on a mechanism that challenges this established view, showing that certain genes can arise directly from segments of non-coding DNA, meaning portions of the genome that previously produced no functional protein at all? These genes, known as de novo genes, seem to spring up almost out of nothing, from what was once considered silent or useless genetic material.

The lab behind this breakthrough

This work was carried out by the Li Zhao lab, a researcher specializing in the study of genetic evolution at Rockefeller University, an American institution recognized for its major contributions to molecular biology and genetics over recent decades. The team's findings were published in 2025 as part of two complementary studies that shed light, from different angles, on this unsuspected mechanism of evolutionary creativity.

These publications rank among the standout scientific discoveries of 2025 according to Rockefeller University itself, which highlighted this work as an illustration of fundamental research's ability to overturn certainties that had stood for decades in the field of evolutionary genetics.

What exactly is a de novo gene

A genetic birth with no direct ancestor

A de novo gene is defined as a gene that emerged recently, on an evolutionary timescale, from a segment of non-coding DNA that previously performed no protein-producing function whatsoever, unlike the vast majority of known genes, which result from the gradual modification of already-existing ancestral genes. This unusual origin makes de novo genes evolutionarily very young compared to the rest of the genome.

Identifying these genes poses a considerable technical challenge for geneticists, since researchers must be able to demonstrate with certainty that a given sequence descends from no known ancestral gene, a task that requires extensive genomic comparisons between closely and distantly related species across the evolutionary tree.

The key role of transcription factors

Researchers in the Li Zhao lab discovered that a small set of transcription factors, proteins that regulate the activation or deactivation of other genes, plays the role of master regulator in the emergence of these de novo genes. These transcription factors appear capable of switching on transcription in previously silent segments of DNA, giving them a first opportunity to carry out a biological function that natural selection can then test.

This discovery of the central role played by a handful of master regulators suggests that the emergence of new genes is not a purely random, scattered process, but could instead be orchestrated, to some extent, by a limited number of clearly identifiable genetic regulation mechanisms.

How these silent genes become functional

The shift from genetic silence to active expression

For a segment of non-coding DNA to eventually become a functional gene, it must first be transcribed into messenger RNA, a step triggered precisely by the action of the transcription factors identified in this research. This initial transcription, even if imperfect or inefficient at first, represents the essential first step toward any eventual biological function useful to the organism.

Once this transcription is underway, natural selection can then begin acting on this newly expressed sequence, favoring variants that provide some advantage to the organism while gradually eliminating those that prove harmful or simply useless to its survival and reproduction.

Regulatory elements shared with neighboring genes

One of the most surprising results of this research concerns the sharing of genetic regulatory elements between de novo genes and their neighboring genes on the genome, suggesting that the emergence of new genes often exploits regulatory machinery already in place for other portions of the genome, rather than requiring an entirely new regulatory system to be built from scratch.

This functional proximity to neighboring genes could explain why some segments of non-coding DNA are more likely than others to give rise to a de novo gene, namely those located physically close to genomic regions already actively regulated by the cell.

Why this discovery upends evolutionary genetics

A challenge to a principle long considered settled

Classical evolutionary genetics long favored the idea that genetic novelty came almost exclusively from the duplication and modification of already-existing genes, a well-documented mechanism widely taught in biology textbooks around the world for decades. The discovery of active, functional de novo genes seriously complicates this view, adding an additional, long-underestimated pathway to the evolutionary manufacture of genes.

This challenge does not mean that the classical mechanism of gene duplication loses its importance, but it does force evolutionary geneticists to acknowledge that the repertoire of mechanisms capable of generating genetic novelty is broader and more creative than previously thought.

Implications that go beyond the species studied

Although this research focused on specific model organisms studied in the lab, the researchers believe this mechanism for the emergence of de novo genes could prove to be far more widespread across the living world than previously assumed, opening up a vast field of research to check for its presence in other species, including humans.

This prospect invites the scientific community to re-examine, in light of these new results, a number of orphan genes already identified in various genomes but whose evolutionary origin had until now remained poorly understood or simply unexplained by classical mechanisms.

What this teaches us about the creativity of evolution

Evolution as a process of ongoing improvisation

This discovery powerfully illustrates the capacity of biological evolution to exploit unexpected genetic resources to generate functional novelty, almost as if nature had a vast reservoir of genetic material waiting in reserve, ready to be recycled and reused as soon as the right regulatory conditions fall into place within the genome.

This capacity for genetic improvisation puts into perspective the sometimes overly rigid image we have of evolution, often reduced to a slow process of incremental modification, when it also appears capable of genuine creative leaps using genetic material previously considered devoid of any biological use.

A window onto still poorly understood mechanisms of the genome

A large portion of the human genome, like that of many other species, is made up of non-coding DNA sequences whose function still remains largely misunderstood by current research, despite decades of intensive study in genomics. This research on de novo genes suggests that some of these sequences, far from being mere useless evolutionary leftovers, could constitute a latent reservoir of future genetic novelty.

This perspective calls for a certain scientific humility in the face of the genome's complexity, with many fundamental mechanisms still waiting to be discovered despite the considerable technological progress made in genetic sequencing over the past twenty years.

The limits and questions that remain open

A demonstrated mechanism, but not yet fully quantified

Despite the importance of this discovery, the researchers themselves acknowledge that much remains to be learned about how often this mechanism for the emergence of de novo genes actually occurs across the different species of the living world, as well as about the proportion of these new genes that actually manage to establish themselves durably in a genome across successive generations.

This scientific caution is all the more justified given that most attempts at genetic emergence of this kind probably fail before they are even detected, with natural selection quickly weeding out sequences that provide no real functional advantage to the organism carrying them.

Open questions about how widespread the phenomenon really is

The two studies published by the Li Zhao lab provide a solid foundation, but they do not yet allow us to conclude with certainty that this mechanism of master regulators governing the emergence of de novo genes applies universally to every species or every type of genome studied by the scientific community.

Further research will be needed to determine whether the mechanism identified at Rockefeller University represents a general rule of genetic evolution or rather a particularity specific to the organisms studied in these two 2025 publications.

Toward new international scientific collaborations

The Li Zhao lab is already collaborating with other comparative genetics teams around the world to check whether the master regulator mechanism observed in their experimental models also shows up in other organisms, from insects to mammals, which would help clarify the true scale of this phenomenon across the living world. These collaborations rely on increasingly powerful bioinformatics tools, capable of comparing thousands of genomes simultaneously to spot signatures of recent genetic emergence.

This collective research dynamic shows just how much modern evolutionary genetics now relies on the cross-referencing of massive datasets and international collaboration, far removed from the image of a lone researcher working in isolation on a scientific problem, a profound shift in how molecular biology has been practiced over the past twenty years.

Conclusion: a new creative pathway on the tree of evolution

A mechanism that enriches our understanding of life

This research on de novo genes and the role of transcription factors in their emergence makes a significant contribution to our understanding of the mechanisms that shape the genetic diversity of life, revealing a long-unsuspected creative pathway arising from DNA sequences once considered functionally silent.

An invitation to rethink how the genome is built

This work from the Li Zhao lab at Rockefeller University serves as yet another reminder that evolutionary genetics remains a living, constantly evolving field of research, where certainties established for decades can be revised in light of new, rigorous, well-documented observations. As sequencing technology keeps improving and computational tools grow more sophisticated, it seems likely that more of these quietly revolutionary mechanisms are still waiting to be uncovered within the vast, largely uncharted stretches of non-coding DNA that make up most of every genome, in humans and countless other species alike.

By Maxime Marquette, columnist

Sources

Primary sources

Rockefeller University — Standout scientific discoveries of 2025 on de novo genes

Nature — Publications on genetic evolution — 2025

Cell — Studies on the emergence of new genes — 2025

Secondary sources

Futura Sciences — Understanding de novo genes — 2025

Sciences et Avenir — Analysis of the de novo gene discovery — 2025

Science et Vie — Decoding the master regulator mechanism — 2025