The evolution of gene expression regulatory networks in yeasts (original) (raw)

Genome evolution in yeasts

Nature, 2004

Identifying the mechanisms of eukaryotic genome evolution by comparative genomics is often complicated by the multiplicity of events that have taken place throughout the history of individual lineages, leaving only distorted and superimposed traces in the genome of each living organism. The hemiascomycete yeasts, with their compact genomes, similar lifestyle and distinct sexual and physiological properties, provide a unique opportunity to explore such mechanisms. We present here the complete, assembled genome sequences of four yeast species, selected to represent a broad evolutionary range within a single eukaryotic phylum, that after analysis proved to be molecularly as diverse as the entire phylum of chordates. A total of approximately 24,200 novel genes were identified, the translation products of which were classified together with Saccharomyces cerevisiae proteins into about 4,700 families, forming the basis for interspecific comparisons. Analysis of chromosome maps and genome redundancies reveal that the different yeast lineages have evolved through a marked interplay between several distinct molecular mechanisms, including tandem gene repeat formation, segmental duplication, a massive genome duplication and extensive gene loss.

Sequencing and comparison of yeast species to identify genes and regulatory elements

Identifying the functional elements encoded in a genome is one of the principal challenges in modern biology. Comparative genomics should offer a powerful, general approach. Here, we present a comparative analysis of the yeast Saccharomyces cerevisiae based on high-quality draft sequences of three related species (S. paradoxus, S. mikatae and S. bayanus). We first aligned the genomes and characterized their evolution, defining the regions and mechanisms of change. We then developed methods for direct identification of genes and regulatory motifs. The gene analysis yielded a major revision to the yeast gene catalogue, affecting approximately 15% of all genes and reducing the total count by about 500 genes. The motif analysis automatically identified 72 genome-wide elements, including most known regulatory motifs and numerous new motifs. We inferred a putative function for most of these motifs, and provided insights into their combinatorial interactions. The results have implications for genome analysis of diverse organisms, including the human.

The topology of the transcription regulatory network in the yeast, Saccharomyces cerevisiae

Physica A: Statistical Mechanics and its Applications, 2003

2 Motivation: A central goal of postgenomic biology is the elucidation of the regulatory relationships among all cellular constituents that together comprise the 'genetic network' of a cell or microorganism. Experimental manipulation of gene activity coupled with the assessment of perturbed transcriptome (i. e., global mRNA expression) patterns represents one approach toward this goal, and may provide a backbone into which other measurements can be later integrated.

Genolevures complete genomes provide data and tools for comparative genomics of hemiascomycetous yeasts

Nucleic Acids Research, 2006

The Gé nolevures online database (http://cbi.labri.fr/ Genolevures/) provides tools and data relative to 4 complete and 10 partial genome sequences determined and manually annotated by the Gé nolevures Consortium, to facilitate comparative genomic studies of hemiascomycetous yeasts. With their relatively small and compact genomes, yeasts offer a unique opportunity for exploring eukaryotic genome evolution. The new version of the Gé nolevures database provides truly complete (subtelomere to subtelomere) chromosome sequences, 25 000 protein-coding and tRNA genes, and in silico analyses for each gene element. A new feature of the database is a novel collection of conserved multi-species protein families and their mapping to metabolic pathways, coupled with an advanced search feature. Data are presented with a focus on relations between genes and genomes: conservation of genes and gene families, speciation, chromosomal reorganization and synteny. The Gé nolevures site includes an area for specific studies by members of its international community.

Polygenic and directional regulatory evolution across pathways in Saccharomyces

Proceedings of the National Academy of Sciences of the United States of America, 2010

The search to understand how genomes innovate in response to selection dominates the field of evolutionary biology. Powerful molecular evolution approaches have been developed to test individual loci for signatures of selection. In many cases, however, an organism's response to changes in selective pressure may be mediated by multiple genes, whose products function together in a cellular process or pathway. Here we assess the prevalence of polygenic evolution in pathways in the yeasts Saccharomyces cerevisiae and S. bayanus. We first established short-read sequencing methods to detect cis-regulatory variation in a diploid hybrid between the species. We then tested for the scenario in which selective pressure in one species to increase or decrease the activity of a pathway has driven the accumulation of cis-regulatory variants that act in the same direction on gene expression. Application of this test revealed a variety of yeast pathways with evidence for directional regulatory evolution. In parallel, we also used population genomic sequencing data to compare protein and cis-regulatory variation within and between species. We identified pathways with evidence for divergence within S. cerevisiae, and we detected signatures of positive selection between S. cerevisiae and S. bayanus. Our results point to polygenic, pathway-level change as a common evolutionary mechanism among yeasts. We suggest that pathway analyses, including our test for directional regulatory evolution, will prove to be a relevant and powerful strategy in many evolutionary genomic applications.

A new system for comparative functional genomics of Saccharomyces yeasts

Genetics, 2013

Whole genome sequencing, particularly in fungi, has progressed at a tremendous rate. More difficult, however, is experimental testing of the inferences about gene function that can be drawn from comparative sequence analysis alone. We present a genome-wide functional characterization of a sequenced but experimentally understudied budding yeast, Saccharomyces bayanus var uvarum (henceforth referred to as S. bayanus), allowing us to map changes over the 20 million years that separate this organism from S. cerevisiae. We first created a suite of genetic tools to facilitate work in S. bayanus. Next, we measured the gene expression response of S. bayanus to a diverse set of perturbations optimized using a computational approach to cover a diverse array of functionally relevant biological responses. The resulting dataset reveals that gene expression patterns are largely conserved, but significant changes may exist in regulatory networks such as carbohydrate utilization and meiosis. In add...

Whole-genome comparative annotation and regulatory motif discovery in multiple yeast species

2003

In [13] we reported the genome sequences of S. paradoxus, S. mikatae and S. bayanus and compared these three yeast species to their close relative, S. cerevisiae. Genome-wide comparative analysis allowed the identification of functionally important sequences, both coding and non-coding. In this companion paper we describe the mathematical and algorithmic results underpinning the analysis of these genomes. We developed methods for the automatic comparative annotation of the four species and the determination of orthologous genes and intergenic regions. The algorithms enabled the automatic identification of orthologs for more than 90% of genes despite the large number of duplicated genes in the yeast genome, and the discovery of recent gene family expansions and genome rearrangements. We also developed a test to validate computationally predicted protein-coding genes based on their patterns of nucleotide conservation. The method has high specificity and sensitivity, and enabled us to revisit the current annotation of S.cerevisiae with important biological implications. We developed statistical methods for the systematic de-novo identification of regulatory motifs. Without making use of coregulated gene sets, we discovered virtually all previously known DNA regulatory motifs as well as several noteworthy novel motifs. With the additional use of gene ontology information, expression clusters and transcription factor binding profiles, we assigned candidate functions to the novel motifs discovered. Our results demonstrate that entirely automatic genome-wide annotation, gene validation, and discovery of regulatory motifs is possible. Our findings are validated by the extensive experimental knowledge in yeast, confirming their applicability to other genomes.

Transcriptional regulators of seven yeast species: Comparative genome analysis — Review

Folia Microbiologica, 2008

The regulation of gene transcription allows yeast cells to respond properly to changing environmental conditions. Several protein complexes take part in this process. They involve RNA polymerase complexes, chromatin remodeling complexes, mediators, general transcription factors and specific transcriptional regulators. Using Saccharomyces cerevisiae as reference, the genomes of six species (Ashbya gossypii, Kluyveromyces lactis, K. waltii, Candida albicans, C. glabrata and Schizosaccharomyces pombe) that are human pathogens or important for the food industry were analyzed for their complement of genes encoding the homologous transcriptional regulators. The number of orthologs identified in a given species correlated with its phylogenetic distance from S. cerevisiae. Many duplicated genes encoding transcriptional regulators in S. cerevisiae and C. glabrata were reduced to one copy in species diverged before the ancestral whole genome duplication. Some transcriptional regulators appear to be specific for S. cerevisiae and probably reflect the physiological differences among species. Phylogenetic analysis and conserved gene order relationships indicate that a similar set of gene families involved in the control of multidrug resistance and oxidative stress response already existed in the common ancestor of the compared fungal species.

Co-expression of adjacent genes in yeast cannot be simply attributed to shared regulatory system

BMC Genomics, 2007

Background: Adjacent gene pairs in the yeast genome have a tendency to express concurrently. Sharing of regulatory elements within the intergenic region of those adjacent gene pairs was often considered the major mechanism responsible for such co-expression. However, it is still in debate to what extent that common transcription factors (TFs) contribute to the co-expression of adjacent genes. In order to resolve the evolutionary aspect of this issue, we investigated the conservation of adjacent pairs in five yeast species. By using the information for TF binding sites in promoter regions available from the MYBS database http://cg1.iis.sinica.edu.tw/\~mybs/, the ratios of TF-sharing pairs among all the adjacent pairs in yeast genomes were analyzed. The levels of coexpression in different adjacent patterns were also compared.

YEASTRACT+: a portal for cross-species comparative genomics of transcription regulation in yeasts

Nucleic Acids Research, 2019

The YEASTRACT+ information system (http://YEASTRACT-PLUS.org/) is a wide-scope tool for the analysis and prediction of transcription regulatory associations at the gene and genomic levels in yeasts of biotechnological or human health relevance. YEASTRACT+ is a new portal that integrates the previously existing YEASTRACT (http://www.yeastract.com/) and PathoYeastract (http://pathoyeastract.org/) databases and introduces the NCYeastract (Non-Conventional Yeastract) database (http://ncyeastract.org/), focused on the so-called non-conventional yeasts. The information in the YEASTRACT database, focused on Saccharomyces cerevisiae, was updated. PathoYeastract was extended to include two additional pathogenic yeast species: Candida parapsilosis and Candida tropicalis. Furthermore, the NCYeastract database was created, including five biotechnologically relevant yeast species: Zygosaccharomyces baillii, Kluyveromyces lactis, Kluyveromyces marxianus, Yarrowia lipolytica and Komagataella phaff...