Review Articles in 2010

Zinc finger nucleases (ZFNs) are versatile tools for making precise modifications to genomes, and their use is now established in a range of model systems. ZFNs are also showing potential in human gene therapy, and several clinical trials are underway.

Evolutionary developmental biology is being advanced by quantitative methods for studying morphology. This Review considers such approaches and emerging insights into interactions between genetic and non-genetic factors, as well as the evolutionary constraints that influence shape.

Are humans evolving? Applying evolutionary biology tools to large-scale medical and epidemiological data sets shows that traits in many human populations are experiencing natural selection and have the genetic potential to respond to it.

How do new gene and protein functions emerge? The authors argue that the effect of mutations on protein structure and activity, the trade-offs of these mutations, and any buffering mechanisms influence whether a given protein function can evolve and the mechanism by which this process is likely to occur.

MicroRNAs are post-transcriptional regulatory molecules that control many developmental and cellular processes. Recent studies have revealed that microRNAs themselves are subject to sophisticated control at various levels, including biogenesis, function and decay. Such regulation greatly contributes to the specific functions of microRNAs.

Accumulating evidence suggests that core promoter recognition complexes have active roles in generating specific transcriptional programmes during development. Other new roles for components of these complexes have also been identified, such as maintaining gene expression states across cell divisions.

Most of the human genome consists of non-protein-coding DNA. This article describes the progress made in annotating this non-coding portion of the genome by combining data from comparative and functional genomics analyses.

The recent availability of sequence data from many yeast species has provided important insights into our understanding of the evolutionary mechanisms in this organism and other eukaryotes. This progress is discussed here, with a focus on the evolution of diverse yeast genome architectures and the multiphyletic origins of yeast among fungi.

Our understanding of the evolution and molecular basis of plant–pathogen interactions has recently been advanced by bringing together genetic and genomic studies of both plants and pathogens. Insights into the strategies used by plants to recognize pathogens may lead to novel agricultural applications.

Which pressures shape the evolution of genomes and phenomes? Using data from comparative genomics and systems biology, the authors analyse this vast field, highlighting the variety of forces at work in addition to some universal themes.

A huge range of genome-scale data sets — including genomic, epigenomic and transcriptomic information — are now available, and it is widely acknowledged that combining several data sets can provide important biological insights. However, there are practical, conceptual and computational challenges to data integration.

Genotype imputation is an important tool for genome-wide association studies as it increases power, aids in fine-mapping of associations and facilitates meta-analyses. This Review provides a guide to and comparison of imputation methods and discusses association testing using imputed data.

The recent sequencing of the genomes of diverse bacteria at different stages of host adaptation is leading to the revision of concepts in microbial evolutionary genomics that were based on studies of laboratory strains. New insights into genetic changes and selective pressures are emerging.

Genome-wide association studies have explained only a small fraction of the genetic basis of complex diseases. This Review argues that rare variants could have a substantial effect on genetic predisposition to common disease, and the authors outline discovery strategies based on whole-genome sequencing for identifying these genetic risk factors.

The authors discuss the evolutionary dynamics of antibiotic resistance in bacteria in relation to the complex interplay between population genetic factors and the spatial and temporal pattern of antibiotic use.

Cohesin and condensin are best known for their roles in mitosis, but these complexes achieve remarkable functional diversity and specificity. Recent studies have demonstrated their involvement in genome organization, gene expression, organismal development and meiosis.

Advances in the synthetic biology field are allowing an expansion beyond small gene networks towards larger biological programs that hold promise for a wide range of applications, including biosensing, therapeutics and the production of biofuels, pharmaceuticals and biomaterials.

Most genome-wide association (GWA) studies have been performed in populations of European descent. This Review discusses the substantial potential and the challenges of extending consideration of GWA studies to diverse worldwide populations.

A view is emerging of the primary cilium as a nexus for developmental signalling pathways. Cilia seem to be specialized for hedgehog signal transduction, and their formation is regulated by other signalling pathways. These findings have implications for human diseases that involve cilia dysfunction.

The rapid induction of specific sets of genes is required for cells to respond to external cues. Transcription of eukaryotic inducible genes is controlled at multiple steps, including activator recruitment and polymerase pausing, and is influenced by chromatin remodelling and signal transduction.