Tracking the Evolution of 3D Gene Organization

The study of eukaryotic genomic organization has been rapidly advancing in recent years, with next generation sequencing technologies, such as Hi-C, providing large scale measurements of 3D genomic organization at unprecedented resolution. It has recently been shown that the distribution of genes in eukaryotic genomes is not random and that their organization is strongly related to gene expression and function. It has also been shown that some level of conservation of this organization exists between organisms.

However, almost all studies of 3D genomic organization analyzed each organism independently from others. Here we propose for the first time a novel approach for inter-organismal analysis of the organization of genes which is based on a network representation of Hi-C data. By utilizing Hi-C data from two fungi – S. cerevisiae and S. pombe – we detect orthologous gene families that underwent changes in their 3D co-localization during evolution. We show that this approach enables identifying biologically relevant modules of co-evolving genes with shared function. These methods can be employed in future studies of genomic evolution, gene function and expression, and in future genomic engineering.