A research team led by the Universitat Autònoma de Barcelona (UAB) has revealed how the genome is reorganised in 3D during male germ cell formation in vertebrates, leading to important new insights in understanding how biodiversity is generated and maintained. The article, published in Nature Communications, analyses species with a common origin dating back over 350 million years.

The study, coordinated by Aurora Ruiz-Herrera, professor and ICREA Acadèmia researcher from the Department of Cellular Biology, Physiology and Immunology, reveals that the tridimensional architecture of the genome, the shape in which the DNA folds inside the cell nucleus, is not static; rather, it undergoes a profound reorganisation during spermatogenesis, an essential process for reproduction.

Through a comparative approach integrating evolutionary genomics and state-of-the-art 3D genome analysis technologies, researchers for the first time analysed how DNA is organised within the cell nucleus of vertebrates, marsupials and reptiles. This approach allowed them to identify both the conserved structural principles and the specific innovations found in each lineage, and reveal how the spatial organisation of the genome has evolved over hundreds of millions of years. In particular, the study shows that fundamental factors such as genome size and chromosome structure determine DNA folding within the nucleus, providing general rules regarding genome architecture in vertebrates.

In addition to describing these patterns, the study generated a new catalogue of genome interactions in germ cells across evolutionary time. This resource will make it possible to reconstruct how the genome may have been organised in vertebrate ancestors and to understand the contribution of these structural changes to the emergence of new biological traits.

The results have significant implications for understanding the mechanisms that generate biological diversity. The three-dimensional organisation of DNA directly influences the regulation of gene expression and, consequently, how cells develop and differentiate. In this context, the study helps link genome architecture to key processes such as reproduction, genetic variability, and species evolution.

Furthermore, the findings provide a fundamental basis for understanding the cellular and molecular foundations of reproduction. Understanding how the genome reorganises during gamete formation is essential for deciphering the mechanisms that ensure the transmission of genetic information across generations and its proper function.

According to Aurora Ruiz-Herrera, principal investigator at the Institute of Biotechnology and Biomedicine (IBB-UAB): “In our group, we investigate how the three-dimensional organisation of the genome contributes to its function and evolution. This study demonstrates that the way DNA folds within the nucleus is key not only to reproduction but also to understanding how biodiversity is generated and maintained over millions of years”.

Laia Marín-Gual, first author of the study, points out that “this advance not only expands knowledge regarding genome function in space but also opens up new avenues for studying the relationship between DNA structure, function, and evolution, with direct implications for reproductive and evolutionary biology”.

The research was made possible through extensive international collaboration coordinated by the UAB, connecting teams across various countries and continents over several years—even amidst the pandemic. The study involved researchers from Australia (UNSW Sydney, the University of Melbourne, and the University of Canberra) and the United States (University of Connecticut). This collective effort enabled the integration of complementary data and approaches to address a key question in evolutionary and reproductive biology.