Reviews & Analysis

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.

Some structures, such as mammalian forelimbs and bird wings, are obviously homologous, but the basis of this is often elusive as the developmental genes involved are not homologous. The author argues that it is instead the gene regulatory networks that are homologous.

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.

Cells use a range of increasingly well understood epigenetic mechanisms to keep transposable elements under control. These silencing mechanisms have been co-opted during the course of evolution to contribute to key aspects of chromosome biology and gene regulation.

Epigenetic modifications provide a possible link between the environment and disease-causing alterations in gene expression. Evidence from animal studies increasingly supports this theory, including recent findings of epigenetically mediated transgenerational alterations in phenotype that are caused by environmental exposure.

Epigenetic modifications are key players in the regulation of fly and yeast telomeres, and recent studies indicate that the same applies in mammalian cells. These findings have implications for our understanding of the roles of telomeres in ageing and cancer.

Successful gastrulation depends on a complex pattern of signalling and gene expression in the early embryo. Uniquely in mammals, this involves both embryonic and extraembryonic tissue. This Review examines how lineages are specified and cell movements are co-ordinated in the early mouse embryo.

Recent technological advances allow epigenetic alterations in cancer to be studied across the whole genome. These approaches are being used to answer key outstanding questions about cancer biology, and to provide new avenues for diagnostics, prognostics and therapy.

Evo–devo has inherited its model organisms from developmental biology. New models must now be chosen to study important phenomena that the original models do not represent. The authors discuss the best criteria for choosing new models.

RNA interference is a potentially powerful therapeutic tool, and several clinical trials are already under way. A detailed mechanistic understanding is helping to optimize the efficacy and safety of RNAi-based treatments, and expanding delivery options promise to broaden its range of applications.

Light influences plant development through extensive transcriptome remodelling. Recent genetic and genome-wide studies have identified crucial components of the hierarchies of transcription factors that control light-regulated transcriptional networks, providing insights into signal integration and the generation of organ-specific responses.

It has long been thought that mutations in regulatory sequences contribute significantly to adaptive evolution, and now empirical evidence is starting to confirm this. But are there qualitative differences between the contributions of regulatory and coding mutations to phenotypic evolution?

Standardization and mass production have been invaluable in biological software, but what about accommodating the specific needs of different experiments? The authors propose a method for generating such customized software infrastructures from existing parts.

The emerging field of community genetics integrates genetics and community ecology. Recently developed tools for studying the genetic bases of the co-adaptive process and co-speciation have the potential to revolutionize how co-evolution is studied, how genes are functionally annotated and how conservation genetics strategies are implemented.

Theories of how sex evolved are now being explored experimentally, particularly regarding the roles of epistasis and drift. Although a generalizable theory remains elusive, new models, including theories that involve genetic architecture and robustness, are helping to understand the available evidence.