Higher Gene Duplicabilities for Metabolic Proteins Than for Nonmetabolic Proteins in Yeast and <Emphasis Type="Italic">E. coli</Emphasis>

Although the evolutionary significance of gene duplication has long been appreciated, it remains unclear what factors determine gene duplicability. In this study we investigated whether metabolism is an important determinant of gene duplicability because cellular metabolism is crucial for the survival and reproduction of an organism. Using genomic data and metabolic pathway data from the yeast (Saccharomyces cerevisiae) and Escherichia coli, we found that metabolic proteins indeed tend to have higher gene duplicability than nonmetabolic proteins. Moreover, a detailed analysis of metabolic pathways in these two organisms revealed that genes in the central metabolic pathways and the catabolic pathways have, on average, higher gene duplicability than do other genes and that most genes in anabolic pathways are single-copy genes.Reviewing Editor: Dr. Rüdiger Cerff     

The metabolic basis of Candida albicans morphogenesis and quorum sensing

Candida albicans is a polymorphic fungus that has the ability to rapidly switch between yeast and filamentous forms. The morphological transition appears to be a critical virulence factor of this fungus. Recent studies have elucidated the signal transduction pathways and quorum sensing molecules that affect the morphological transition of C. albicans. The metabolic mechanisms that recognize, and respond to, such signaling molecules and promote the morphological changes at a system level, however, remain unknown. Here we review the metabolic basis of C. albicans morphogenesis and we discuss the role of primary metabolic pathways and quorum sensing molecules in the morphogenetic process. We have reconstructed, in silico, the central carbon metabolism and sterol biosynthesis of C. albicans based on its genome sequence, highlighting the metabolic pathways associated with the dimorphic transition and virulence as well as pathways involved in the biosynthesis of important quorum sensing molecules.     

Cross-talk in plant hormone signalling: what Arabidopsis mutants are telling us

Genetic screens have been extremely useful in identifying genes involved in hormone signal transduction. However, although these screens were originally designed to identify specific components involved in early hormone signalling, mutations in these genes often confer changes in sensitivity to more than one hormone at the whole-plant level. Moreover, a variety of hormone response genes has been identified through screens that were originally designed to uncover regulators of sugar metabolism. Together, these facts indicate that the linear representation of the hormone signalling pathways controlling a specific aspect of plant growth and development is not sufficient, and that hormones interact with each other and with a variety of developmental and metabolic signals. Following the advent of arabidopsis molecular genetics we are beginning to understand some of the mechanisms by which a hormone is transduced into a cellular response. In this Botanical Briefing we review a subset of genes in arabidopsis that influence hormonal cross-talk, with emphasis on the gibberellin, abscisic acid and ethylene pathways. In some cases it appears that modulation of hormone sensitivity can cause changes in the synthesis of an unrelated hormone, while in other cases a hormone response gene defines a node of interaction between two response pathways. It also appears that a variety of hormones may converge to regulate the turnover of important regulators involved in growth and development. Examples are cited of the recent use of suppressor and enhancer analysis to identify new nodes of interaction between these pathways.     

The soma-germline communication: implications for somatic and reproductive aging

Aging is characterized by a functional decline in most physiological processes, including alterations in cellular metabolism and defense mechanisms. Increasing evidence suggests that caloric restriction extends longevity and retards age-related diseases at least in part by reducing metabolic rate and oxidative stress in a variety of species, including yeast, worms, flies, and mice. Moreover, recent studies in invertebrates – worms and flies, highlight the intricate interrelation between reproductive longevity and somatic aging (known as disposable soma theory of aging), which appears to be conserved in vertebrates. This review is specifically focused on how the reproductive system modulates somatic aging and vice versa in genetic model systems. Since many signaling pathways governing the aging process are evolutionarily conserved, similar mechanisms may be involved in controlling soma and reproductive aging in vertebrates.     

Metabolome analysis during the morphological transition of Candida albicans

Candida albicans is an opportunistic pathogen of humans with significant mortality in severely immunocompromised patients. The ability to switch from yeast to hyphal morphology and vice versa, in response to various environmental cues, is believed to be a critical virulence factor of this fungus. However, the mechanisms that recognize such environmental signals and trigger the morphological change at a system level are still not clearly understood. Therefore, we have compared the metabolite profiles of C. albicans cells growing under different hyphae-inducing conditions to the metabolite profiles of growing yeast cells. Surprisingly our results suggest an overall downregulation of cellular metabolism during the yeast to hyphal morphological transition. Among the metabolic pathways involved in the central carbon metabolism, we have found seventeen that were significantly downregulated in all three hyphae-inducing conditions. This indicates that these central carbon metabolic pathways are likely to be intrinsically involved in the downstream effects of the morphogenetic process.     

Yeast orthologues associated with glycerol transport and metabolism

Glycerol is a key compound in the regulation of several metabolic pathways in Saccharomyces cerevisiae. From this yeast most of the genes involved in glycerol consumption, production and transport are now available. Some of the mechanisms involving glycerol metabolism and transport are common to other yeasts. This work presents a search for GPD1/2, GUT1, GUP1/2 and FPS1 orthologues in a series of hemiascomycetous yeasts. All the genes cloned were able to complement S. cerevisiae mutant phenotypes and presented a high degree of similarity to the corresponding genes in this yeast. A phylogenetic analysis is presented. The allocation of GUP genes in the membrane bound O-acyl transferases (MBOAT) family is suggested as more consistent than their inclusion in the TC-DB/glycerol uptake family.     

Biodiversity in sulfur metabolism in hemiascomycetous yeasts

The evolution of the metabolism of sulfur compounds among yeast species was investigated. Differences between species were observed in the cysteine biosynthesis pathway. Most yeast species possess two pathways leading to cysteine production, the transsulfuration pathway and the O-acetyl-serine (OAS) pathway, with the exception of Saccharomyces cerevisiae and Candida glabrata, which only display the transsulfuration pathway, and Schizosaccharomyces pombe, which only have the OAS pathway. An examination of the components of the regulatory network in the different species shows that it is conserved in all the species analyzed, as its central component Met4p was shown to keep its functional domains and its partners were present. The analysis of the presence of genes involved in the catabolic pathway shows that it is evolutionarily conserved in the sulfur metabolism and leads us to propose a role for two gene families which appeared to be highly conserved. This survey has provided ways to understand the diversity of sulfur metabolism products among yeast species through the reconstruction of these pathways. This diversity could account for the difference in metabolic potentialities of the species with a biotechnological interest.     

Unraveling the mystery of cancer metabolism in the genesis of tumor-initiating cells and development of cancer

Robust anaerobic metabolism plays a causative role in the origin of cancer cells; however, the oncogenic metabolic genes, factors, pathways, and networks in genesis of tumor-initiating cells (TICs) have not yet been systematically summarized. In addition, the mechanisms of oncogenic metabolism in the genesis of TICs are enigmatic. In this review, we discussed multiple cancer metabolism-related genes (MRGs) that are overexpressed in TICs and are responsible for inducing pluripotent stem cells. Moreover, we summarized that oncogenic metabolic genes and onco-metabolites induce metabolic reprogramming, which switches normal mitochondrial oxidative phosphorylation to cancer anaerobic metabolism, triggers epigenetic, genetic, and environmental alterations, drives the generation of TICs, and boosts the development of cancer. Importantly, cancer metabolism is controlled by positive and negative metabolic regulators. Positive oncogenic metabolic regulators, including key oncogenic metabolic genes, onco-metabolites, hypoxia, and an acidic environment, promote oncogenic metabolic reprogramming and anaerobic metabolism. However, dysfunction of negative metabolic regulators, including defects in p53, PTEN, and LKB1-AMPK-mTOR pathways, enhances cancer metabolism. Loss of the metabolic balance results in oncogenic metabolic reprogramming, genesis of TICs, and tumorigenesis. Collectively, this review provides new insight into the role and mechanism of these oncogenic metabolisms in the genesis of TICs and tumorigenesis. Accordingly, targeting key oncogenic genes, onco-metabolites, pathways, networks, and the acidic cancer microenvironment appears to be an attractive strategy for novel anti-tumor treatment.     

Simon Labbé's work on iron and copper homeostasis

Iron and copper have a wealth of functions in biological systems, which makes them essential micronutrients for all living organisms. Defects in iron and copper homeostasis are directly responsible for diseases, and have been linked to impaired development, metabolic syndromes and fungal virulence. Consequently, it is crucial to gain a comprehensive understanding of the molecular bases of iron- and copper-dependent proteins in living systems. Simon Labbé maintains parallel programs on iron and copper homeostasis using the fission yeast Schizosaccharomyces pombe (Schiz. pombe) as a model system. The study of fission yeast transition-metal metabolism has been successful, not only in discerning the genes and pathways functioning in Schiz. pombe, but also the genes and pathways that are active in mammalian systems and for other fungi.     

Genome sequence of the lignocellulose-bioconverting and xylose-fermenting yeast Pichia stipitis

Xylose is a major constituent of plant lignocellulose, and its fermentation is important for the bioconversion of plant biomass to fuels and chemicals. Pichia stipitis is a well-studied, native xylose-fermenting yeast. The mechanism and regulation of xylose metabolism in P. stipitis have been characterized and genes from P. stipitis have been used to engineer xylose metabolism in Saccharomyces cerevisiae. We have sequenced and assembled the complete genome of P. stipitis. The sequence data have revealed unusual aspects of genome organization, numerous genes for bioconversion, a preliminary insight into regulation of central metabolic pathways and several examples of colocalized genes with related functions. The genome sequence provides insight into how P. stipitis regulates its redox balance while very efficiently fermenting xylose under microaerobic conditions.