Evolving Cell Cycle: New Genes Discovered by EPFL Scientists

In a groundbreaking study published in *Cell Genomics*, scientists at the École Polytechnique Fédérale de Lausanne (EPFL) have revealed that recently evolved genes play a crucial role in cell division, a fundamental biological process that has existed since the earliest bacteria. This discovery highlights the continuous evolution of cellular mechanisms, even for processes as ancient as the cell cycle.

Every day, human bodies undergo approximately 330 billion cell divisions, a vital process for maintaining health and function. The cell cycle, which governs these divisions, has evolved significantly in more complex organisms. Understanding the role of recently evolved genes in this cycle could provide insights into various diseases, including cancer.

The research team, led by Romain Forey and Cyril Pulver, both associated with Didier Trono's group at EPFL, embarked on this interdisciplinary project by combining cell cycle biology and genomics. They developed a detailed atlas of human cell cycle gene activity, which is now publicly accessible for further research. This collaboration also included Alex Lederer from Gioele La Manno's lab, who contributed crucial analyses pertaining to CRISPR interference data.

"Romain oversaw all of the wet lab experiments and brought in his cell cycle expertise, while I managed the genomics analyses," stated Cyril Pulver. He emphasized that the project benefitted from collaborative discussions across disciplinary boundaries, allowing for a comprehensive understanding of the cell cycle.

The researchers focused on a specific group of genes that encode transcription factors—proteins that regulate gene expression. Their findings revealed that several of these transcription factors, which are essential for guiding cells through the cell cycle, have emerged in more recent evolutionary history. Notably, the gene ZNF519, which is exclusive to primates, was identified as a key player in this process. When ZNF519 was disabled, cells exhibited difficulties in accurately replicating their DNA, essential for successful division, consequently slowing their growth. Furthermore, ZNF274, present in mammals but absent in older reptiles and fish, was found to influence the timing of genomic duplication prior to mitosis, an important factor for genome organization and maintenance.

Dr. Didier Trono, a prominent researcher in the field, expressed optimism about the implications of this study. "Our research contributes a comprehensive resource regarding human cell cycle gene expression and perturbations, which we hope will be of use to our colleagues worldwide," he stated. The integration of new genetic components into such fundamental processes not only enhances the understanding of the cell cycle but may also illuminate the reasons behind the varying prevalence and behavior of certain cancers and developmental disorders in humans compared to other mammals.

This research represents a significant advancement in cell biology and genomics, offering critical insights for future studies aimed at understanding the complexities of human health and disease. As research progresses, the implications of these findings could lead to improved strategies for tackling diseases that arise from dysregulated cell cycles, underscoring the importance of ongoing genetic research in understanding human biology.