![]() ![]() The genetic code offers a convenient (and universal) mechanism for specifying polar versus non-polar amino acids: a purine at base two of a codon virtually guarantees the selection of a polar amino acid, while a pyrimidine in the second base tends to guarantee a non-polar amino acid. The membrane components of the cell are largely composed of proteins containing non-polar amino acids whereas by contrast, water-soluble proteins (such as those present at the center of the cell) have mostly polar amino acids on their surface. One way of looking at it is that the cell embodies an entropy gradient, with a high-entropy aqueous environment in the center, and a low-entropy (which is to say, highly structured) envelope, encompassing a membrane and structural components, at the periphery. ![]() High-level overviewĪ key characteristic of cellular life is encapsulation: cells have an inside, and an outside, with durable structures separating the two. In the present study, we aim for a top-down bioinformatics investigation of moonlighting genes, in which we look for high-level clues and pan-genomic causes and effects. Of note is that many genes involved in moonlighting are ancient, highly conserved genes, again pointing to underlying processes that are fundamental-perhaps even primordial, in some sense. GAPDH, enolase, DnaK, GroEL, Ef-Tu, superoxide dismutase) serve in moonlighting roles across diverse hosts? Because the same proteins are often found in moonlighting roles across phyla, it seems likely that the phenomenon is made possible by processes that are fundamental to all life. Many fundamental questions remain unanswered: How do these genes acquire multiple functions? How do they gain access to the exterior of the cell, in the absence of secretion-system partners? Why do some metabolic enzymes get secreted while many others do not? And how is it that the same proteins (e.g. The manually curated MoonProt database now lists over 300 such genes, spanning host organisms that range from bacteria to yeast, protists, archeons, plants, and mammals. Such examples include gene products with well-known cytosolic roles that somehow end up on the surface of the cell, or are excreted into culture media. In the 30 years since glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was found to have a secondary role on the cell surface of pathogenic streptococci 2, many other examples of moonlighting have been uncovered. To our knowledge, no secretion-system partners have been identified for these proteins. Paradoxically, these proteins often have a cytosolic location as well as being found on the exterior of the cell. Moonlighting genes are genes that encode proteins having multiple distinct and often unrelated functions 1. Evolutionary and other implications of these findings are discussed. This leads to high potential for escape of moonlighting proteins to the cell surface. On the basis of this and other findings, we offer a model in which we propose that moonlighting gene products are likely to escape the cell through gaps in the cell wall and membrane, at wall/membrane construction sites and we propose that antisense ORFs produce “membrane-sticky” protein products, effectively binding moonlighting-gene DNA to the cell membrane in porous areas where intensive cell-wall/cell-membrane construction is underway. We also find that moonlighting genes tend to co-locate with genes involved in cell wall, cell membrane, or cell envelope production. We find that moonlighting genes harbor putative antisense open reading frames (ORFs) rich in codons for non-polar amino acids. In this study, we present a simple bioinformatics probe that allows us to rank genes by antisense translation potential, and we show that this probe enriches, reliably, for moonlighting genes across a variety of organisms. Their ubiquity and functional diversity raise many questions as to their origins, evolution, and role in the cell cycle. These genes occur across all domains of life. The area under each section of the plot represents the entropy change associated with heating the substance through an interval Δ T.Moonlighting genes encode for single polypeptide molecules that perform multiple and often unrelated functions. \): Heat capitity/temperature as a function of temperature ![]()
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