Review Articles in 2007

Relatively little is known about what underlies mutation rate variation at an empirical level, particularly in multicellular eukaryotes. The authors review theoretical and empirical results to provide a framework for future studies of why and how mutation rate evolves in multicellular species.

Numerous inherited diseases, with a surprisingly diverse range of phenotypes, are being found to arise from mutations that affect translation. Studies of these diseases are beginning to provide new insights into the functions of the protein synthesis machinery and its regulators.

Spatial and temporal patterns of metazoan DNA replication are emerging as being dynamically regulated by tissue-specific and developmental cues, and by epigenetic modifications. These features might allow coordination with transcription and chromatin assembly, and enable changes in gene expression patterns.

Expression signatures have tremendous power to identify new cancer subtypes and to predict clinical outcomes. Using these signatures as surrogate phenotypes researchers can link diverse experimental systems to dissect the complexity of tumorigenesisin vivo.

A key challenge in gene therapy is vector targeting to specific cells, while avoiding effects on other tissues. Several strategies have been developed recently to enable targeting of the main viral vectors, moving them a step closer to clinical use.

RNA-binding proteins orchestrate the post-transcriptional co-regulation of subsets of mRNAs that encode functionally related proteins, thereby contributing to the coordination of gene expression in eukaryotes. Understanding the dynamics of such ribonucleoprotein structures might provide insights into some complex diseases and the regulation of gene expression during development.

REST can act as a hub for the recruitment of multiple chromatin-modifying enzymes. Research into its function and that of its corepressors has provided new insight into how chromatin-modifying proteins cooperate to regulate gene expression, and how alterations in this function cause disease.

Malaria is a major cause of mortality in the developing world. Genetics and genomics are now greatly assisting our understanding of this disease, through linkage and association studies of the malaria parasite,Plasmodium.

The popularity ofCaenorhabditis elegans as a model organism is paralleled by the range of resources that are available to worm researchers. This Review provides a guide to existing C. elegansresources, and highlights areas for future development.

The positioning of individual genes within the nucleus affects their expression levels. The inner face of the nuclear envelope is key to this method of regulating expression, with active genes preferentially locating to nuclear pores in a manner that might be heritable.

Powerful tools for carrying out large-scale genetic-interaction screens have made budding yeast a leading model system for understanding gene networks. Studies in yeast also provide a basis for extending our understanding to networks in more complex eukaryotes.

The transcription regulation networks that control gene expression consist of a series of recurring logical wiring patterns — network motifs. By understanding the properties of these simple motifs we can start to understand the complexity of whole networks.

Although they do not get cancer naturally, genetically manipulatedDrosophila melanogasterare a useful model for studying tumours. Recent results highlight the importance of asymmetric cell division and proper spindle alignment for preventing stem cells from giving rise to tumours.

Genome-wide analyses of transcriptional output in eukaryotes have revealed an unanticipated transcriptome complexity. These findings imply a complex, interleaved genomic organization, in which individual sequences carry multiple and overlapping informational content. The authors discuss the evidence for, and functional and evolutionary consequences of, this organization.

Genome-wide discovery and characterization of core promoters has revealed that most mammalian genes are transcribed from multiple promoters, each of them starting from multiple nucleotide positions, not directed by a TATA box. The authors propose a new classification of promoters.

Animal models are crucial for understanding the pathogenesis of human disease and provide a system in which to develop and test new therapies. The zebrafish offers unique advantages over other vertebrates and is therefore rapidly emerging as a model organism for a wide range of human diseases, both genetic and acquired, and for therapeutic drug discovery and development.

One promising way of attempting to understand the complexity of biological processes is to model them mathematically. Such models can help predict the wider biological effects of local interactions and are now producing testable hypotheses about the workings of developmental systems.

Genome-wide technologies, functional experimentation in model systems and clinical validation are beginning to identify genetic and epigenetic alterations that underlie metastatic disease. These genetic determinants are distinct from those that mediate malignant transformation and can be classified into metastasis initiation, metastasis progression and metastasis virulence genes.

Reduction in gene flow between varieties is part of the process of speciation. One underappreciated reason for such a reduction is hybrid necrosis — when the hybrid offspring have phenotypes that resemble the results of pathogen attack and environmental stress.

How do stem cells keep the genes that drive differentiation in a repressed state, while maintaining the ability to express them in the future? Increasing evidence indicates that distinctive epigenetic traits underlie this unique aspect of stem-cell biology.