Transcriptional robustness and protein interactions are associated in yeast

BackgroundRobustness to insults, both external and internal, is a characteristic feature of life. One level of biological organization for which noise and robustness have been extensively studied is gene expression. Cells have a variety of mechanisms for buffering noise in gene expression, but it is not completely clear what rules govern whether or not a given gene uses such tools to maintain appropriate expression.ResultsHere, we show a general association between the degree to which yeast cells have evolved mechanisms to buffer changes in gene expression and whether they possess protein-protein interactions. We argue that this effect bears an affinity to epistasis, because yeast appears to have evolved regulatory mechanisms such that distant changes in gene copy number for a protein-protein interaction partner gene can alter a gene's expression. This association is not unexpected given recent work linking epistasis and the deleterious effects of changes in gene dosage (i.e., the dosage balance hypothesis). Using gene expression data from artificial aneuploid strains of bakers' yeast, we found that genes coding for proteins that physically interact with other proteins show less expression variation in response to aneuploidy than do other genes. This effect is even more pronounced for genes whose products interact with proteins encoded on aneuploid chromosomes. We further found that genes targeted by transcription factors encoded on aneuploid chromosomes were more likely to change in expression after aneuploidy.ConclusionsWe suggest that these observations can be best understood as resulting from the higher fitness cost of misexpression in epistatic genes and a commensurate greater regulatory control of them

The rarity of gene shuffling in conserved genes

BACKGROUND: Among three sources of evolutionary innovation in gene function - point mutations, gene duplications, and gene shuffling (recombination between dissimilar genes) - gene shuffling is the most potent one. However, surprisingly little is known about its incidence on a genome-wide scale. RESULTS: We have studied shuffling in genes that are conserved between distantly related species. Specifically, we estimated the incidence of gene shuffling in ten organisms from the three domains of life: eukaryotes, eubacteria, and archaea, considering only genes showing significant sequence similarity in pairwise genome comparisons. We found that successful gene shuffling is very rare among such conserved genes. For example, we could detect only 48 successful gene-shuffling events in the genome of the fruit fly Drosophila melanogaster which have occurred since its common ancestor with the worm Caenorhabditis elegans more than half a billion years ago. CONCLUSION: The incidence of gene shuffling is roughly an order of magnitude smaller than the incidence of single-gene duplication in eukaryotes, but it can approach or even exceed the gene-duplication rate in prokaryotes. If true in general, this pattern suggests that gene shuffling may not be a major force in reshaping the core genomes of eukaryotes. Our results also cast doubt on the notion that introns facilitate gene shuffling, both because prokaryotes show an appreciable incidence of gene shuffling despite their lack of introns and because we find no statistical association between exon-intron boundaries and recombined domains in the two multicellular genomes we studied

Article Comparative Genomics as a Time Machine: How Relative Gene Dosage and Metabolic Requirements Shaped the Time-dependent Resolution of Yeast Polyploidy

Abstract Using a phylogenetic model of evolution after genome duplication (i.e., polyploidy) and 12 yeast genomes with a shared genome duplication, I show that the loss of duplicate genes after that duplication occurred in three phases. First, losses that occurred immediately after the event were biased toward genes functioning in DNA repair and organellar functions. Then, the main group of duplicate losses appear to have been shaped by a requirement to maintain balance in protein levels: There is a strong statistical association between the number of protein interactions a gene's product is involved in and its propensity to have remained in duplicate. Moreover, when duplicated genes with interactions were lost, it was more common than expected for both members of an interaction pair to have been lost on the same branch of the phylogeny. Finally, in the third phase of the resolution process, overretention of duplicated enzymes carrying high flux and of duplicated genes involved in transcriptional regulation became dominant. I speculate that initial retention of such genes by a requirement to maintain gene dosage set the stage for the later functional changes that then maintained these duplicates for long periods

Patterns of gene conversion in duplicated yeast histones suggest strong selection on a coadapted macromolecular complex

We find evidence for interlocus gene conversion in five duplicated histone genes from six yeast species. The sequences of these duplicated genes, surviving from the ancient genome duplication, show phylogenetic patterns inconsistent with the well-resolved orthology relationships inferred from a likelihood model of gene loss after the genome duplication. Instead, these paralogous genes are more closely related to each other than any is to its nearest ortholog. In addition to simulations supporting gene conversion, we also present evidence for elevated rates of radical amino acid substitutions along the branches implicated in the conversion events. As these patterns are similar to those seen in ribosomal proteins that have undergone gene conversion, we speculate that in cases where duplicated genes code for proteins that are a part of tightly interacting complexes, selection may favor the fixation of gene conversion events in order to maintain high protein identities between duplicated copies

Increased glycolytic flux as an outcome of whole-genome duplication in yeast

Correction to: Molecular Systems Biology 3:129. doi:10.1038/msb4100170; published online 31 July 200

Functional Partitioning of Yeast Co-Expression Networks after Genome Duplication

Several species of yeast, including the baker's yeast Saccharomyces cerevisiae, underwent a genome duplication roughly 100 million years ago. We analyze genetic networks whose members were involved in this duplication. Many networks show detectable redundancy and strong asymmetry in their interactions. For networks of co-expressed genes, we find evidence for network partitioning whereby the paralogs appear to have formed two relatively independent subnetworks from the ancestral network. We simulate the degeneration of networks after duplication and find that a model wherein the rate of interaction loss depends on the “neighborliness” of the interacting genes produces networks with parameters similar to those seen in the real partitioned networks. We propose that the rationalization of network structure through the loss of pair-wise gene interactions after genome duplication provides a mechanism for the creation of semi-independent daughter networks through the division of ancestral functions between these daughter networks

A Conserved Mammalian Protein Interaction Network

Physical interactions between proteins mediate a variety of biological functions, including signal transduction, physical structuring of the cell and regulation. While extensive catalogs of such interactions are known from model organisms, their evolutionary histories are difficult to study given the lack of interaction data from phylogenetic outgroups. Using phylogenomic approaches, we infer a upper bound on the time of origin for a large set of human protein-protein interactions, showing that most such interactions appear relatively ancient, dating no later than the radiation of placental mammals. By analyzing paired alignments of orthologous and putatively interacting protein-coding genes from eight mammals, we find evidence for weak but significant co-evolution, as measured by relative selective constraint, between pairs of genes with interacting proteins. However, we find no strong evidence for shared instances of directional selection within an interacting pair. Finally, we use a network approach to show that the distribution of selective constraint across the protein interaction network is non-random, with a clear tendency for interacting proteins to share similar selective constraints. Collectively, the results suggest that, on the whole, protein interactions in mammals are under selective constraint, presumably due to their functional roles.A˚.P.B. is supported by Ga˚lo¨stiftelsen Stipendium fo¨r ho¨gre utlandsstudier. C.M.H. is supported by a National Library of Medicine Biomedical and Health Informatics Training Fellowship [LM007089-19]. G.C.C. is supported by the Reproductive Biology Group of the Food for the 21st Century program at the University of Missouri. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Altered patterns of gene duplication and differential gene gain and loss in fungal pathogens

<p>Abstract</p> <p>Background</p> <p>Duplication, followed by fixation or random loss of novel genes, contributes to genome evolution. Particular outcomes of duplication events are possibly associated with pathogenic life histories in fungi. To date, differential gene gain and loss have not been studied at genomic scales in fungal pathogens, despite this phenomenon's known importance in virulence in bacteria and viruses.</p> <p>Results</p> <p>To determine if patterns of gene duplication differed between pathogens and non-pathogens, we identified gene families across nine euascomycete and two basidiomycete species. Gene family size distributions were fit to power laws to compare gene duplication trends in pathogens <it>versus </it>non-pathogens. Fungal phytopathogens showed globally altered patterns of gene duplication, as indicated by differences in gene family size distribution. We also identified sixteen examples of gene family expansion and five instances of gene family contraction in pathogenic lineages. Expanded gene families included those predicted to be important in melanin biosynthesis, host cell wall degradation and transport functions. Contracted families included those encoding genes involved in toxin production, genes with oxidoreductase activity, as well as subunits of the vacuolar ATPase complex. Surveys of the functional distribution of gene duplicates indicated that pathogens show enrichment for gene duplicates associated with receptor and hydrolase activities, while euascomycete pathogens appeared to have not only these differences, but also significantly more duplicates associated with regulatory and carbohydrate binding functions.</p> <p>Conclusion</p> <p>Differences in the overall levels of gene duplication in phytopathogenic species <it>versus </it>non-pathogenic relatives implicate gene inventory flux as an important virulence-associated process in fungi. We hypothesize that the observed patterns of gene duplicate enrichment, gene family expansion and contraction reflect adaptation within pathogenic life histories. These adaptations were likely shaped by ancient, as well as contemporary, intimate associations with monocot hosts.</p

Author Correction: Genome-Guided Phylo-Transcriptomic Methods and the Nuclear Phylogenetic Tree of the Paniceae Grasses

The original version of this Article contained an error in the title of the paper, where the word “Phylogenetic” was incorrectly given as “Phylogentic”. This has now been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Information file

Distinct C4 sub-types and C3 bundle sheath isolation in the Paniceae grasses.

Funder: U.S. Department of Agriculture; Id: http://dx.doi.org/10.13039/100000199Funder: University of Missouri; Id: http://dx.doi.org/10.13039/100007165In C4 plants, the enzymatic machinery underpinning photosynthesis can vary, with, for example, three distinct C4 acid decarboxylases being used to release CO2 in the vicinity of RuBisCO. For decades, these decarboxylases have been used to classify C4 species into three biochemical sub-types. However, more recently, the notion that C4 species mix and match C4 acid decarboxylases has increased in popularity, and as a consequence, the validity of specific biochemical sub-types has been questioned. Using five species from the grass tribe Paniceae, we show that, although in some species transcripts and enzymes involved in multiple C4 acid decarboxylases accumulate, in others, transcript abundance and enzyme activity is almost entirely from one decarboxylase. In addition, the development of a bundle sheath isolation procedure for a close C3 species in the Paniceae enables the preliminary exploration of C4 sub-type evolution