Gaining further insights into the evolution and function of de novo genes, Li Zhao’s research team from the University of California recently published their work in Nature Communications. These genes are therefore novel and not inherited from a common ancestor. This groundbreaking study details how these genes are activated and regulated within cellular networks, providing a deeper insight into evolutionary biology and gene regulation.
When Zhao opened her lab eight years ago, soon after de novo genes were first discovered, Zhao did not know how to study them. Since that time, she and her team have worked tirelessly to identify hundreds of genes. Their primary interest right now is the ways in which these genes are expressed, specifically in the testis of fruit flies, or Drosophila. This led the research team to find that only ~10% of known transcription factors regulate de novo genes. These TFs are key regulators of gene expression.
The research doesn’t stop at mapping networks of genes. It offers new perspectives on their development, as well as the possible impacts of any breakdowns in these systems. Zhao states, “The more we know about de novo regulation, the more information we have about gene expression and regulation itself.”
The Journey of Discovery
Zhao’s deep dive into de novo genes started from a simple question asked to her a few years ago. She recalls, “We knew nothing about this—it was a question, asked during a casual conversation, that I had not even thought about. I informed him that we were not able to respond to that question at this time. I slipped in that I honestly had no clue when we’d be able to offer an answer. As a result, he became motivated to begin a journey that has since lasted almost ten years. Her lab has been hard at work garnering gene expression data from hundreds of thousands of cells.
To elucidate the complexities of Drosophila testis at the cellular level, the research team used cutting-edge single-cell sequencing technologies. This targeted method enabled them to watch the complex choreography of how exactly de novo genes get switched on and regulated. Zhao emphasized the complexity of this process, stating, “Expression and regulation is more complex than we think.”
The lab developed transgenic fruit flies to have additional or fewer copies of the transcription factor. They could then measure how environmental changes affected the expression of DNGs. This novel methodology uncovered fascinating information about the regulatory mechanisms that control gene activation.
Implications for Evolutionary Biology
The research carried out by Zhao’s lab not only has practical implications for furthering our understanding of evolutionary biology. This work uncovers additional complexities beyond the simplicity of the de novo genes once described. This turns our current understanding of gene regulation on its head. Zhao explains that two critical angles need consideration: “One talks about how the cellular environment regulates new genes. The second is how genes interact to control each other’s expression.”
This subtle appreciation might make for a new paradigm in thinking about the evolution of gene networks by scientists. With the recent advances, it’s becoming clearer how these de novo genes arise. This investigation will elucidate their function in evolutionary pattern formation and demonstrate how perturbation of these regulatory pathways can result in multiple pathobiological conditions.
Zhao’s work is groundbreaking because it provides a new basis for exploring gene creation and expression. With the newfound knowledge on de novo genes, researchers can explore additional questions related to genetics and evolution that have remained unanswered for decades.
Future Directions
As Li Zhao embarks on her future research, the goal is to continue to peel back the layers of the onion that is de novo gene regulation. Combined with prior work, the lab’s findings strengthen our understanding of genetic architectures. In doing so, they open up new opportunities for future experiments to investigate the evolution of genetic networks in more detail.
This research doesn’t stop with fruit flies. Not only would it allow us to redefine our perception of bigger biological picture, but it would allow us to address genetic disorders arising from abominable gene regulation. Zhao’s team demonstrates that learning about de novo genes is much more than curiosity. It is indispensable in helping us untangle the mysteries of life.