Functional Redundancy and Expression Divergence among Gene Duplicates in Yeast (original) (raw)
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Molecular Biology and Evolution, 2007
Expression divergence of duplicate genes is widely believed to be important for their retention and evolution of new function, although the mechanism that determines their expression divergence remains unclear. We use a genetical genomics approach to explore divergence in genetical control of yeast duplicate genes created by a whole-genome duplication that occurred about 100 MYA and those with a younger duplication age. The analysis reveals that duplicate genes have a significantly higher probability of sharing common genetic control than pairs of singleton genes. The expression quantitative trait loci (eQTLs) have diverged completely for a high proportion of duplicate pairs, whereas a substantially larger proportion of duplicates share common regulatory motifs after 100 Myr of divergent evolution. The similarity in both genetical control and cis motif structure for a duplicate pair is a reflection of its evolutionary age. This study reveals that up to 20% of variation in expression between ancient duplicate gene pairs in the yeast genome can be explained by both cis motif divergence (;8%) and by trans eQTL divergence (;10%). Initially, divergence in all 3 aspects of cis motif structure, trans-genetical control, and expression evolves coordinately with the coding sequence divergence of both young and old duplicate pairs. These findings highlight the importance of divergence in both cis motif structure and trans-genetical control in the diverse set of mechanisms underlying the expression divergence of yeast duplicate genes.
Pervasive and persistent redundancy among duplicated genes in yeast
PLoS genetics, 2008
The loss of functional redundancy is the key process in the evolution of duplicated genes. Here we systematically assess the extent of functional redundancy among a large set of duplicated genes in Saccharomyces cerevisiae. We quantify growth rate in rich medium for a large number of S. cerevisiae strains that carry single and double deletions of duplicated and singleton genes. We demonstrate that duplicated genes can maintain substantial redundancy for extensive periods of time following duplication (,100 million years). We find high levels of redundancy among genes duplicated both via the whole genome duplication and via smaller scale duplications. Further, we see no evidence that two duplicated genes together contribute to fitness in rich medium substantially beyond that of their ancestral progenitor gene. We argue that duplicate genes do not often evolve to behave like singleton genes even after very long periods of time.
Nucleic Acids Research, 2010
Duplicate genes tend to have a more variable expression program than singleton genes, which was thought to be an important way for the organism to respond and adapt to fluctuating environment. However, the underlying molecular mechanisms driving such expression variation remain largely unexplored. In this work, we first rigorously confirmed that duplicate genes indeed have higher gene expression variation than singleton genes in several aspects, i.e. responses to environmental perturbation, between-strain divergence, and expression noise. To investigate the underlying mechanism, we further analyzed a previously published expression dataset of yeast segregants produced from genetic crosses. We dissected the observed expression divergence between segregant strains into cis-and trans-variabilities, and demonstrated that trans-regulation effect can explain larger fraction of the expression variation than cis-regulation effect. This is true for both duplicate genes and singleton genes. In contrast, we found, between a pair of sister paralogs, cis-variability explains more of the expression divergence between the paralogs than trans-variability. We next investigated the presence of cis-and trans-features that are associated with elevated expression variations. For cis-acting regulation, duplicate genes have higher genetic diversity in their promoters and coding regions than singleton genes. For transacting regulation, duplicate and singleton genes are differentially regulated by chromatin regulators and transcription factors, and duplicate genes are more severely affected by the deletion of histone tails. These results showed that both cisand trans-factors have great effect in causing the increased expression variation of duplicate genes, and explained the previously observed differences in transcription regulation between duplicate genes and singleton genes.
Comparative analysis indicates regulatory neofunctionalization of yeast duplicates
Genome Biology, 2007
Background: Gene duplication provides raw material for the generation of new functions, but most duplicates are rapidly lost due to the initial redundancy in gene function. How gene function diversifies following duplication is largely unclear. Previous studies analyzed the diversification of duplicates by characterizing their coding sequence divergence. However, functional divergence can also be attributed to changes in regulatory properties, such as protein localization or expression, which require only minor changes in gene sequence.
Molecular Biology and Evolution, 2010
Although divergence in expression is thought to be a hallmark of functional dispersal between paralogs postduplication, there is currently a limited understanding of the mechanisms underlying the necessary transcriptional alterations as recent studies have suggested that only a very small proportion of expression variation could be explained by transcriptional variation between paralogs. To further this understanding, we examined comprehensively curated regulatory interactions and genomewide nucleosome occupancy in budding yeast to specifically determine the contribution of cis-elements to expression divergence between extant duplicates. We found that divergence in activation by transcription factors plays a more important role in expression divergence of paralogs than previously appreciated; further, analysis of promoter chromatin structure demonstrated that differential nucleosome organization is coupled with divergent expression of paralogs. By incorporating information of cis-elements encoding transcriptional regulation and chromatin structure, we improved the fraction of expression variation that was previously shown to be explained based on known cistranscriptional effects by approximately 3-fold. Taken together, our analysis highlights the importance of chromatin divergence involved in expression evolution between paralogs.
DNA Research
Gene duplication is an important source of novelties and genome complexity. What genes are preserved as duplicated through long evolutionary times can shape the evolution of innovations. Identifying factors that influence gene duplicability is therefore an important aim in evolutionary biology. Here, we show that in the yeast Saccharomyces cerevisiae the levels of gene expression correlate with gene duplicability, its divergence, and transcriptional plasticity. Genes that were highly expressed before duplication are more likely to be preserved as duplicates for longer evolutionary times and wider phylogenetic ranges than genes that were lowly expressed. Duplicates with higher expression levels exhibit greater divergence between their gene copies. Duplicates that exhibit higher expression divergence are those enriched for TATAcontaining promoters. These duplicates also show transcriptional plasticity, which seems to be involved in the origin of adaptations to environmental stresses in yeast. While the expression properties of genes strongly affect their duplicability, divergence and transcriptional plasticity are enhanced after gene duplication. We conclude that highly expressed genes are more likely to be preserved as duplicates due to their promoter architectures, their greater tolerance to expression noise, and their ability to reduce the noise-plasticity conflict.
Genomic Background Predicts the Fate of Duplicated Genes: Evidence From the Yeast Genome
Genetics, 2004
Gene duplication with subsequent divergence plays a central role in the acquisition of genes with novel function and complexity during the course of evolution. With reduced functional constraints or through positive selection, these duplicated genes may experience accelerated evolution. Under the model of subfunctionalization, loss of subfunctions leads to complementary acceleration at sites with two copies, and the difference in average rate between the sequences may not be obvious. On the other hand, the classical model of neofunctionalization predicts that the evolutionary rate in one of the two duplicates is accelerated. However, the classical model does not tell which of the duplicates experiences the acceleration in evolutionary rate. Here, we present evidence from the Saccharomyces cerevisiae genome that a duplicate located in a genomic region with a low-recombination rate is likely to evolve faster than a duplicate in an area of high recombination. This observation is consistent with population genetics theory that predicts that purifying selection is less effective in genomic regions of low recombination (Hill-Robertson effect). Together with previous studies, our results suggest the genomic background (e.g., local recombination rate) as a potential force to drive the divergence between nontandemly duplicated genes. This implies the importance of structure and complexity of genomes in the diversification of organisms via gene duplications.
Loss of protein interactions and regulatory divergence in yeast whole-genome duplicates
Genomics, 2009
Whole-genome duplications are important for the growth of genome complexity. We investigated various factors involved in the evolution of yeast whole-genome duplicates (ohnologs) making emphasis on the analysis of protein interactions. We found that ohnologs have a lower number of protein interactions compared with small-scale duplicates and singletons (by about − 40%). The loss of interactions was proportional to their initial number and independent of ohnolog position in the protein interaction network. A faster evolving member of an ohnolog pair has a lower number of interactions compared to its counterpart. The Gene Ontology mapping of non-overlapping and overlapping interactants of paired ohnologs reveals a sharp asymmetry in GO terms related to regulation. The fraction of these terms is much higher in nonoverlapping interactants (compared to overlapping interactants and total dataset). Network clustering coefficient is lower in ohnologs, yet they show an increased density of protein interactions restricted within the whole ohnologs set. These facts suggest that subfunctionalization (or subneofunctionalization) reflected in the loss of protein interactions was a prevailing process in the divergence of ohnologs, which distinguishes them from small-scale duplicates. The loss of protein interactions was associated with the regulatory divergence between the members of an ohnolog pair. A small-scale modularity (reflected in clustering coefficient) probably was not important for ohnologs retention, yet a larger-scale modularity could be involved in their evolution.
created by whole-genome duplication in yeast
Identification of orthologous genes across species becomes challenging in the presence of a whole genome duplication (WGD). We present a probabilistic method for identifying orthologs that considers all possible orthology/paralogy assignments for a set of genomes with a shared WGD (here five yeast species). This approach allows us to estimate how confident we can be in the orthology assignments in each genomic region.
Rapid divergence in expression between duplicate genes inferred from microarray data
Trends in Genetics, 2002
For more than 30 years, expression divergence has been considered as a major reason for retaining duplicated genes in a genome, but how often and how fast duplicate genes diverge in expression has not been studied at the genomic level. Using yeast microarray data, we show that expression divergence between duplicate genes is significantly correlated with their synonymous divergence (K S ) and also with their nonsynonymous divergence (K A ) if K A ≤ ≤ 0.3. Thus, expression divergence increases with evolutionary time, and K A is initially coupled with expression divergence. More interestingly, a large proportion of duplicate genes have diverged quickly in expression and the vast majority of gene pairs eventually become divergent in expression. Indeed, more than 40% of gene pairs show expression divergence even when K S is ≤ ≤ 0.10, and this proportion becomes > >80% for K S > > 1.5. Only a small fraction of ancient gene pairs do not show expression divergence.