Reviews & Analysis

The correct location and structure of centromeric chromatin is essential for accurate chromosome segregation. This Review brings together recent findings relating to the centromeric histone H3 variant, CENP-A, and discusses possible models for the establishment and propagation of centromeric chromatin.

Recent studies have shown that there is enormous variation in the number of chemosensory receptor genes among the genomes of different organisms. Much of the variation can be explained by adaptation, but random duplication and deletion of genes also have important roles.

Recent studies have advanced our understanding of gene classes that tend to undergo duplication, and how natural selection acts on them. The co-option of pre-existing, secondary protein functions is emerging as a widespread feature in the evolution of genetic novelty through gene duplication.

Selectionists and neutralists invoke different theories to explain the emergence of evolutionary innovation. Our recent understanding of molecular phenotypes makes it possible to reconcile these two views by proposing that neutral variants prepare the ground for adaptive mutations to occur.

It is increasingly clear that genetic factors contribute to the different manifestation of human diseases between males and females. Genotype-by-sex interactions on disease risk might be common in humans; ignoring such effects in searches for disease-associated genes may result in important loci being missed.

Although centromeres are generally known for their involvement in attaching chromosomes to microtubules, more diverse roles for these chromosomal regions are now becoming clear. Recent evidence implicates centromeres as central to crucial steps in meiotic chromosome segregation.

Recent genome-wide association studies have identified many genes associated with metabolic disorders. However, systems-biology approaches could give improved insights into the complex involvement of genetic and environmental factors.

The recent advent of cell type molecular fingerprinting has yielded initial insights into the evolutionary interrelationships of cell types between remote animal phyla, allowing the definition of some key principles of cell type diversification in animal evolution.

MicroRNAs exert their regulatory effects by potently repressing some targets, fine-tuning other targets or coordinately regulating target batteries. MicroRNA-mediated control can also be reversible. These regulatory themes underlie the exploitation of microRNA control in diverse biological circuits.

Current approaches for dissecting complex traits largely ignore epiallelic variation. To overcome this limitation the authors propose a quantitative approach to identifying the dynamic interplay between DNA sequence, chromatin and environmental contributions to the phenotype, across generations and developmental time points.

Histone mRNAs, the only cellular mRNAs that are not polyadenylated, end in a conserved stem–loop that performs the functions of the poly(A) tail in mRNA metabolism and that is required for cell-cycle regulation and regulating the balance of the production of variant and canonical histones.

Epistasis is fundamental to the structure and function of genetic pathways and to the evolutionary dynamics of complex genetic systems. High-throughput functional genomics, systems-level approaches and advances in molecular evolution are spurring renewed interest in understanding and quantifying epistatic interactions.

For decades, mutant mice have been used to model human disease and to functionally annotate the mammalian genome. Advances in generating mutants on a large scale — through both forward and reverse genetic approaches — have accelerated progress, as documented by this history of mouse mutagenesis.

Social insects have been so successful because individuals cooperate, bringing direct benefit to the community and indirect benefit to themselves. The genetic and molecular basis of this cooperativity, and of the conflict that often underlies it, is beginning to be uncovered.

Many biological processes are regulated by circadian rhythms, which keep them in time with the Earth's 24-hour light–dark cycle. Elucidating the genetic control of circadian rhythms will help to understand the many diseases that can result when the clock goes wrong.

What makes us human? This question can only be approached by integrating disparate disciplines, from molecular comparisons of genetic and genomic differences in humans and close evolutionary relatives, of organ-systems changes, and by considering the influence of the environment and culture.

In the past 16 years, there has been much excitement in the area of DNA vaccine development for a range of medical conditions. The recent licensure of DNA vaccines for veterinary use bodes well for applications in humans, in which progress has been slower.

Mitochondrial DNA reproduces asexually and is therefore susceptible to the accumulation of deleterious mutations. Recent results suggest that there is purifying selection against such mutations within the female germ line, which has important consequences for studies of evolution and human disease.

In addition to their roles in mRNA quality control, nonsense-mediated mRNA decay (NMD) factors are emerging as multitasking players in gene expression and genome integrity. These functions involve both the NMD process itself and pathways that are apparently unconnected to NMD.

Wiki pages and commenting Interconnected networks of databases and analytical tools will be needed to drive biological research in the twenty-first century. What should such a cyberinfrastructure look like? Which components are in place already? And how do we progress from here?