Highways of gene sharing in prokaryotes

The extent to which lateral genetic transfer has shaped microbial genomes has major implications for the emergence of community structures. We have performed a rigorous phylogenetic analysis of > 220,000 proteins from genomes of 144 prokaryotes to determine the contribution of gene sharing to current prokaryotic diversity, and to identify highways of sharing between lineages. The inferred relationships suggest a pattern of inheritance that is largely vertical, but with notable exceptions among closely related taxa, and among distantly related organisms that live in similar environments.

Inherent size constraints on prokaryote gene networks due to "accelerating" growth

Networks exhibiting accelerating growth have total link numbers growing faster than linearly with network size and either reach a limit or exhibit graduated transitions from nonstationary-to-stationary statistics and from random to scale-free to regular statistics as the network size grows. However, if for any reason the network cannot tolerate such gross structural changes then accelerating networks are constrained to have sizes below some critical value. This is of interest as the regulatory gene networks of single-celled prokaryotes are characterized by an accelerating quadratic growth and are size constrained to be less than about 10,000 genes encoded in DNA sequence of less than about 10 megabases. This paper presents a probabilistic accelerating network model for prokaryotic gene regulation which closely matches observed statistics by employing two classes of network nodes (regulatory and non-regulatory) and directed links whose inbound heads are exponentially distributed over all nodes and whose outbound tails are preferentially attached to regulatory nodes and described by a scale-free distribution. This model explains the observed quadratic growth in regulator number with gene number and predicts an upper prokaryote size limit closely approximating the observed value. (c) 2005 Elsevier GmbH. All rights reserved.

The BAR domain proteins: Molding membranes in fission, fusion, and phagy

The Bin1/amphiphysin/Rvs167 (BAR) domain proteins are a ubiquitous protein family. Genes encoding members of this family have not yet been found in the genomes of prokaryotes, but within eukaryotes, BAR domain proteins are found universally from unicellular eukaryotes such as yeast through to plants, insects, and vertebrates. BAR domain proteins share an N-terminal BAR domain with a high propensity to adopt alpha-helical structure and engage in coiled-coil interactions with other proteins. BAR domain proteins are implicated in processes as fundamental and diverse as fission of synaptic vesicles, cell polarity, endocytosis, regulation of the actin cytoskeleton, transcriptional repression, cell-cell fusion, signal transduction, apoptosis, secretory vesicle fusion, excitation-contraction coupling, learning and memory, tissue differentiation, ion flux across membranes, and tumor suppression. What has been lacking is a molecular understanding of the role of the BAR domain protein in each process. The three-dimensional structure of the BAR domain has now been determined and valuable insight has been gained in understanding the interactions of BAR domains with membranes. The cellular roles of BAR domain proteins, characterized over the past decade in cells as distinct as yeasts, neurons, and myocytes, can now be understood in terms of a fundamental molecular function of all BAR domain proteins: to sense membrane curvature, to bind GTPases, and to mold a diversity of cellular membranes.

Protein disulfide isomerase: the structure of oxidative folding

Cellular functions hinge on the ability of proteins to adopt their correct folds, and misfolded proteins can lead to disease. Here, we focus on the proteins that catalyze disulfide bond formation, a step in the oxidative folding pathway that takes place in specialized cellular compartments. In the endoplasmic reticulum of eukaryotes, disulfide formation is catalyzed by protein disulfide isomerase (PDI); by contrast, prokaryotes produce a family of disulfide bond (Dsb) proteins, which together achieve an equivalent outcome in the bacterial periplasm. The recent crystal structure of yeast PDI has increased our understanding of the function and mechanism of PDI. Comparison of the structure of yeast PDI with those of bacterial DsbC and DsbG reveals some similarities but also striking differences that suggest directions for future research aimed at unraveling the catalytic mechanism of disulfide bond formation in the cell.