Distinct chromosomal niches in the genome of S. cerevisiae provide the background for genomic innovation and shape the fate of gene duplicates

Abstract

Gene duplication is a major source of genomic innovation in all eukaryotes, with large proportions of genes being the result of either small-scale (SSD) or genome-wide duplication (WGD) events. In the model unicellular eukaryote Saccharomyces cerevisiae, of which nearly one third of the genome corresponds to gene duplicates, the two modes of duplication have been shown to follow different evolutionary fates, with SSD genes being more prone to acquire novel functionalities (neofunctionalization) and WGD more likely to retain different parts of the original ancestral function (subfunctionalization). Having previously described aspects of functional compartmentalization for the genes of S. cerevisiae, in this work we set out to investigate the existence of positional preferences of gene duplicates. We found that SSD and WGD genes are organized in distinct gene clusters that are, furthermore, segregated, occupying different regions, with SSD being more peripheral and WGD more centrally positioned close to centromeric chromatin. Duplicate gene clusters differ from the rest of the genome in terms of gene size and spacing, gene expression variability and regulatory complexity. What is more interesting, some of these properties are also shared by singleton genes residing in duplicate-rich regions in a position-dependent manner. Our analysis further reveals particular chromatin architectures in the promoters of duplicate genes, which are generally longer, with less pronounced nucleosome-free regions, strong structural constraints and a larger number of regulatory elements. Such structural features appear to be important for gene evolution as we find SSD gene-pair co-expression to be strongly associated with the similarity of nucleosome positioning patterns. We propose that specific regions of the yeast genome provide a favourable environment for the generation and maintenance of small-scale gene duplicates. The existence of such genomic "niches" is supported by the enrichment of these regions in singleton genes bearing similarities with gene "relics", remnants of recent duplications that have reverted to single gene status. Our findings provide a valuable framework for the study of genomic innovation and suggest taking into account positional preferences in the study of gene emergence and fixation in experimentally and naturally evolving populations.