Co-expression of adjacent genes in yeast cannot be simply attributed to shared regulatory system (original) (raw)
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Molecular evolution in the yeast transcriptional regulation network
Journal of Experimental Zoology …, 2004
We analyze the structure of the yeast transcriptional regulation network, as revealed by chromatin immunoprecipitation experiments, and characterize the molecular evolution of both its transcriptional regulators and their target (regulated) genes. We test the hypothesis that highly connected genes are more important to the function of gene networks. Three lines of evidence, the rate of molecular evolution of network genes, the rate at which network genes undergo gene duplication, and the effects of synthetic null mutation in network genes provide no strong support for this hypothesis. In addition, we ask how network genes diverge in their transcriptional regulation after duplication. Both loss (subfunctionalization) and gain (neofunctionalization) of transcription factor binding play a role in this divergence, which is often rapid. On one hand, gene duplicates experience a net loss in the number of transcription factors binding to them, indicating the importance of losing transcription factor binding sites after gene duplication. On the other hand, the number of transcription factors that bind to highly diverged duplicates is significantly greater than expected if loss of binding played the only role in the divergence of duplicate genes.
Evolution of cis-regulatory elements in yeast de novo and duplicated new genes
BMC Genomics, 2012
Background: New genes that originate from non-coding DNA rather than being duplicated from parent genes are called de novo genes. Their short evolution time and lack of parent genes provide a chance to study the evolution of cis-regulatory elements in the initial stage of gene emergence. Although a few reports have discussed cis-regulatory elements in new genes, knowledge of the characteristics of these elements in de novo genes is lacking. Here, we conducted a comprehensive investigation to depict the emergence and establishment of cis-regulatory elements in de novo yeast genes.
Gene, 2012
It is generally accepted that genes are regulated by the interactions between transcription factors (TFs) and their binding sites (TFBSs). Some studies have demonstrated that nucleotide variants at variable positions in TFBSs affect yeast gene regulation. Furthermore, variable positions in TFBSs in association with distinct accompanying regulatory motifs of other TFs (i.e., co-TFs) can also impact gene regulation in eukaryotes. Given that, even low-affinity TF-DNA interactions are abundant in vivo; we used both low-and high-affinity TFBSs and performed a genome-wide analysis of associations between variable positions and co-TFs. We found that, in Saccharomyces cerevisiae, approximately 14% of the variable positions in TFBSs demonstrate such associations. These associations occurred in close proximity on the same promoters (i.e., highly co-localized). Moreover, such associations were highly conserved between sensu stricto yeasts and also influenced gene expression, which were consistent with enriched functional categories.
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.
Roles of Trans and Cis Variation in Yeast Intraspecies Evolution of Gene Expression
Molecular Biology and Evolution, 2009
Both cis and trans mutations contribute to gene expression divergence within and between species. We used Saccharomyces cerevisiae as a model organism to estimate the relative contributions of cis and trans variations to the expression divergence between a laboratory (BY) and a wild (RM) strain of yeast. We examined whether genes regulated by a single transcription factor (TF; single input module, SIM genes) or genes regulated by multiple TFs (multiple input module, MIM genes) are more susceptible to trans variation. Because a SIM gene is regulated by a single immediate upstream TF, the chance for a change to occur in its trans-acting factors would, on average, be smaller than that for a MIM gene. We chose 232 genes that exhibited expression divergence between BY and RM to test this hypothesis. We examined the expression patterns of these genes in a BY-RM coculture system and in a BY-RM diploid hybrid. We found that trans variation is far more important than cis variation for expression divergence between the two strains. However, because in 75% of the genes studied, cis variation has significantly contributed to expression divergence, cis change also plays a significant role in intraspecific expression evolution. Interestingly, we found that the proportion of genes with diverged expression between BY and RM is larger for MIM genes than for SIM genes; in fact, the proportion tends to increase with the number of transcription factors that regulate the gene. Moreover, MIM genes are, on average, subject to stronger trans effects than SIM genes, though the difference between the two types of genes is not conspicuous.
Evolution of genome-wide gene regulation in the budding yeast cell-division cycle
Genome-wide regulation of gene expression involves a dynamic epigenetic structure which generates an organism's life-cycle. Although changes in gene expression during development have broad effects on many basic phenomena including cell growth, differentiation, morphogenesis, and disease progression, the evolutionary forces influencing gene expression dynamics and gene regulation remain largely unknown, due to the nature of gene expression as a polygenic, quantitative trait. Moreover, gene expression is regulated differentially over time, so evolutionary forces may be influenced by developmental context. To advance the understanding of evolution in the context of the life-cycle, the architecture of gene expression timing control and its influence on expression dynamics must be revealed. This dissertation presents two experimental investigations of the evolution of genes and related structural regions and time-dependent gene expression, using the budding yeasts Saccharomyces cerevisiae and Saccharomyces paradoxus and their mitotic celldivision cycle as model organism and life-cycle. Comparative methodologies were employed to analyze genome-wide patterns of genetic and phenotypic diversity within and between species. Analysis of several dozen yeast genomes reveals a dominant evolutionary mode of purifying selection. Despite limited genetic variability, differences in transcriptional regulation appear to contribute predominantly to interspecies divergence, and altered post-transcriptional regulation of ribosomal genes may have altered the timing of each species' transition from vegetative growth to reproduction, a classic life-history trait. In addition, natural variation in genome-wide gene expression was measured as a time-series through the mitotic cell-division cycle of 10 yeast lines, including one outgroup species. Despite levels of variation consistent with strong stabilizing selection, transcriptome coexpression dynamics have diverged significantly within and between species. A model involving timing pattern changes explains 61% of the between-genome variation in expression dynamics, suggesting that the major mode of transcriptome evolution involves changes in timing (heterochrony) rather than changes in levels (heterometry) of expression. Analysis of heterochrony patterns suggests that timing control is organized into distinct and dynamically-autonomous modules. Divergence in expression dynamics may be explained by pleiotropic changes in modular timing control. Genome-wide gene regulation may utilize a general architecture comprised of multiple discrete event timelines, whose superposition could produce combinatorial complexity in timing patterns.
Molecular biology and evolution, 2013
Gene expression evolution can be caused by changes in cis-or trans-regulatory elements or both. As cis and trans regulation operate through different molecular mechanisms, cis and trans mutations may show different inheritance patterns and may be subjected to different selective constraints. To investigate these issues, we obtained and analyzed gene expression data from two Saccharomyces cerevisiae strains and their hybrid, using high-throughput sequencing. Our data indicate that compared with other types of genes, those with antagonistic cis-trans interactions are more likely to exhibit over-or underdominant inheritance of expression level. Moreover, in accordance with previous studies, genes with trans variants tend to have a dominant inheritance pattern, whereas cis variants are enriched for additive inheritance. In addition, cis regulatory differences contribute more to expression differences between species than within species, whereas trans regulatory differences show a stronger association between divergence and polymorphism. Our data indicate that in the trans component of gene expression differences genes subjected to weaker selective constraints tend to have an excess of polymorphism over divergence compared with those subjected to stronger selective constraints. In contrast, in the cis component, this difference between genes under stronger and weaker selective constraint is mostly absent. To explain these observations, we propose that purifying selection more strongly shapes trans changes than cis changes and that positive selection may have significantly contributed to cis regulatory divergence.