An enduring problem in biology is explaining how novel functions of genes originated and those diverge between species. Despite detailed studies on the functional evolution a few proteins, molecular mechanisms by which protein have evolved are almost entirely unknown. Here, we show that polyalanine tract homeodomain transcription factor HoxA11 arose stem-lineage mammals as an autonomous repress...

Crystals of baculovirus-expressed adeno-associated virus serotype 1 (AAV1) capsids have been grown in the rhombohedral space group R32 (unit-cell parameters a = 254.7 A, alpha = 62.3 degrees) and shown to diffract X-rays to at least 2.5 A resolution. The diffraction data were subsequently processed and reduced with an overall R(sym) of 12.3% and a completeness of 89.0%. Based on the unit-cell v...

Human proteins containing polyalanine tracts tend to have runs of other amino acids and their open reading frames (ORFs) display a biased codon usage. Their alanine, glycine, proline, and histidine content strongly correlates with the GC content of the third codon base, suggesting that the compositional specificity of these proteins is dictated to a great extent by the evolution of their ORFs.

OBJECTIVES Severe congenital diarrhea occurs in approximately half of patients with Aristaless-Related Homeobox (ARX) null mutations. The cause of this diarrhea is unknown. In a mouse model of intestinal Arx deficiency, the prevalence of a subset of enteroendocrine cells is altered, leading to diarrhea. Because polyalanine expansions within the ARX protein are the most common mutations found in...

Stochastic search algorithms can be used to perform rapid six-dimensional molecular-replacement searches. A molecular-replacement procedure has been developed that uses an evolutionary algorithm to simultaneously optimize the orientation and position of a search model in a unit cell. Here, the performance of this algorithm and its dependence on search model quality and choice of target function...

We compare two recently proposed methods for the characterization of phase transitions in small systems. The validity and usefulness of these approaches are studied for the cases of the q=4 and q=5 Potts model, i.e., systems where a thermodynamic limit and exact results exist. Guided by this analysis we then discuss the helix-coil transition in polyalanine, an example of structural transitions ...

This report describes a 6 year old girl with late onset central hypoventilation syndrome due to a heterozygous polyalanine repeat expansion mutation in the PHOX2B gene. This report aims to increase the awareness of this condition among physicians to allow earlier clinical and genetic diagnosis and management of cases of unexplained hypoventilation.

In this issue of Neuron, Todd et al. (2013) reveal that noncanonical repeat associated non-AUG (RAN) translation occurs on nonexpanded (CGG)30-50 and premutation (CGG)59-160 repeats, associated with the FMR1 gene, suggesting that the polyglycine and polyalanine products might have natural and pathogenic roles.