Functional Analysis of Gene Duplications in Saccharomyces cerevisiae

Abstract

Gene duplication can occur on two scales: whole-genome duplications (WGD) and smaller-scale duplications (SSD) involving individual genes or genomic segments. Duplication may result in functionally redundant genes or diverge in function through neofunctionalization or subfunctionalization. The effect of duplication scale on functional evolution has not yet been explored, probably due to the lack of global knowledge of protein function and different times of duplication events. To address this question, we used integrated Bayesian analysis of diverse functional genomic data to accurately evaluate the extent of functional similarity and divergence between paralogs on a global scale. We found that paralogs resulting from the whole-genome duplication are more likely to share interaction partners and biological functions than smaller-scale duplicates, independent of sequence similarity. In addition, WGD paralogs show lower frequency of essential genes and higher synthetic lethality rate, but instead diverge more in expression pattern and upstream regulatory region. Thus, our analysis demonstrates that WGD paralogs generally have similar compensatory functions but diverging expression patterns, suggesting a potential of distinct evolutionary scenarios for paralogs that arose through different duplication mechanisms. Furthermore, by identifying these functional disparities between the two types of duplicates, we reconcile previous disputes on the relationship between sequence divergence and expression divergence or essentiality.

Small-scale copy number variation and large-scale changes in gene expression

“…Thus, a new feature could emerge immediately, augmenting or modifying previous function. The possibility that duplicated genes are not redundant is supported by a number of evolutionary studies (25,53). This is not to say that large-scale gene expression given a gene duplication event must be the norm.…”

“…In some instances, gene copy number is integrated into dynamic models of regulation to account for cell-to-cell variability of regulatory elements found on plasmids (23). More commonly, recent studies have attempted to identify statistical relations between CNV and fitness (4), protein interactions (24), or combinations of both (25). To understand the progression from CNV to changes in phenotype to changes in fitness, it seems necessary to carefully examine gene regulation itself.…”

Posttranslational regulation impacts the fate of duplicated genes

“…Several studies have shown that the mode of duplication (WGD vs. SSD) has different effects on the evolution of the genome (7,41,42). Because SSDs occur continuously and at various times, it is not possible to repeat the evolutionary analysis that was possible for the WGD.…”

Prevalent Role of Gene Features in Determining Evolutionary Fates of Whole-Genome Duplication Duplicated Genes in Flowering Plants

“…In addition to the discovery that WGD duplicated genes are functionally biased (Blanc and Wolfe, 2004;Seoighe and Gehring, 2004;Aury et al, 2006;Freeling, 2008;Wu et al, 2008;Schnable et al, 2009), several gene features were identified to associate with their retention probability, such as gene complexity (He and Zhang, 2005), gene length , essentiality (He and Zhang, 2006), expression level (Seoighe and Wolfe, 1999), evolutionary rates , number of protein interactions (Guan et al, 2007;Hakes et al, 2007), functional category (Blanc and Wolfe, 2004), alternative splicing status (Kopelman et al, 2005), protein structure (Papp et al, 2003;Liang et al, 2008), position in the protein-protein interaction network Wu and Qi, 2010), and number of phosphorylation sites (Amoutzias et al, 2010). However, it is unlikely that merely one or two features alone can account for the evolutionary process of duplicated genes, as many of these features are correlated to each other.…”