The Role of Nucleosome Positioning in the Evolution of Gene Regulation

Abstract

A comparative genomics study maps nucleosomes across the entire genomes of 12 fungal species, identifying multiple distinct mechanisms linking changes in chromatin architecture to evolution of gene regulation.

Abstract

Chromatin organization plays a major role in gene regulation and can affect the function and evolution of new transcriptional programs. However, it can be difficult to decipher the basis of changes in chromatin organization and their functional effect on gene expression. Here, we present a large-scale comparative genomic analysis of the relationship between chromatin organization and gene expression, by measuring mRNA abundance and nucleosome positions genome-wide in 12 Hemiascomycota yeast species. We found substantial conservation of global and functional chromatin organization in all species, including prominent nucleosome-free regions (NFRs) at gene promoters, and distinct chromatin architecture in growth and stress genes. Chromatin organization has also substantially diverged in both global quantitative features, such as spacing between adjacent nucleosomes, and in functional groups of genes. Expression levels, intrinsic anti-nucleosomal sequences, and trans-acting chromatin modifiers all play important, complementary, and evolvable roles in determining NFRs. We identify five mechanisms that couple chromatin organization to evolution of gene regulation and have contributed to the evolution of respiro-fermentation and other key systems, including (1) compensatory evolution of alternative modifiers associated with conserved chromatin organization, (2) a gradual transition from constitutive to trans-regulated NFRs, (3) a loss of intrinsic anti-nucleosomal sequences accompanying changes in chromatin organization and gene expression, (4) re-positioning of motifs from NFRs to nucleosome-occluded regions, and (5) the expanded use of NFRs by paralogous activator-repressor pairs. Our study sheds light on the molecular basis of chromatin organization, and on the role of chromatin organization in the evolution of gene regulation.

Author Summary

Divergence in gene regulation plays a major role in organismal evolution. Evidence suggests that changes in the packaging of eukaryotic genomes into chromatin can underlie the evolution of divergent gene expression patterns. Here, we explore the role of chromatin structure in regulatory evolution by whole-genome measurements of nucleosome positions and mRNA levels in 12 yeast species spanning ∼250 million years of evolution. We find several distinct ways in which changes in chromatin structure are associated with changes in gene expression. These include changes in promoter accessibility, changes in promoter chromatin architecture, and changes in the accessibility of specific transcription factor binding sites. In many cases, changes in chromatin architecture are coupled to physiological diversity, including the evolution of a respiration- or fermentation-based lifestyle, mating behavior, salt tolerance, and broad aspects of genomic structure. Together, our data will provide a rich resource for future investigations into the interplay between chromatin structure, gene regulation, and evolution.