Stem cells

p53 induces differentiation of mouse embryonic stem cells by suppressing Nanog expression. Lin, T. et al. Nature Cell Biol. 26 December 2004 (10.1038/ncb1211)

Responding effectively to DNA damage is particularly important in embryonic stem (ES) cells. However, ES cells do not undergo efficient apoptosis or cell-cycle arrest in response to DNA damage. Lin and colleagues show that the tumour suppressor p53 triggers ES-cell differentiation by inhibiting expression of Nanog. This renders them susceptible to apoptosis and cell-cycle arrest, providing a mechanism to avoid the potentially disastrous consequences of DNA damage.

Sex chromosome evolution

A gradual process of recombination restriction in the evolutionary history of the sex chromosomes in dioecious plants. Nicolas, M. et al. PLoS Biol. 3, e4 (2004)

Mammalian sex chromsomes are thought to have evolved through gradual loss of recombination between a pair of initially homologous autosomes, leaving a small pseudoautosomal region (PAR) that retains the ability to recombine. Nicolas et al. studied X-linked genes in plants that use an X–Y sex-determination system. Patterns of divergence of these genes from their Y-chromosome homologues indicated that sex chromosomes evolved through similar mechanisms in dioecious plants and mammals.

Human disease genetics

Loss-of-function mutation in tryptophan hydroxylase-2 identified in unipolar major depression. Zhang, X. et al. Neuron 45, 11–16 (2005)

Decreased serotonin levels are implicated in several neuropsychiatric disorders, but the genetic basis of this is unclear. Zhang and colleagues identified a SNP in a gene required for serotonin synthesis — tryptophan hydroxylase 2 — resulting in a protein with reduced function. Among patients with unipolar major depression, 9 out of 87 carried this SNP, compared with 3 out of 219 in a control group, implicating defective serotonin synthesis as a major risk factor for unipolar depression and related conditions.

Molecular evolution

The rate of DNA evolution: effects of body size and temperature on the molecular clock. Gillooly, J. F. et al. Proc. Natl Acad. Sci. USA 102, 140–145 (2005)

The assumption that underlies the classical 'molecular clock' is that molecular evolution occurs at a universally constant rate. This study investigates the causes of the observed heterogeneity in the rate of molecular evolution. The authors' model, which is validated experimentally, indicates that the molecular clock ticks at different rates depending on metabolic status, and could explain rate variation among genes, taxa or temperatures. Importantly, this model supports the existence of a single molecular clock.