Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole-genome sequencing to perform an unbiased comprehensive screen to discover the somatic mutations in a sample from an individual with sAML and genotyped the loci containing these mutations in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we found suggestive evidence of an increased risk of progression to sAML associated with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3' end of introns, and the alterations in U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis.     

Genomic revelations of a mutualism: the pea aphid and its obligate bacterial symbiont

The symbiosis of the pea aphid Acyrthosphion pisum with the bacterium Buchnera aphidicola APS represents the best-studied insect obligate symbiosis. Here we present a refined picture of this symbiosis by linking pre-genomic observations to new genomic data that includes the complete genomes of the eukaryotic and prokaryotic symbiotic partners. In doing so, we address four issues central to understanding the patterns and processes operating at the A. pisum/Buchnera APS interface. These four issues include: (1) lateral gene transfer, (2) host immunity, (3) symbiotic metabolism, and (4) regulation.     

Preliminary assessment of velvet ant (Hymenoptera: Mutillidae) diversity in the deserts of southern California

The deserts of southern California house a diverse and unique insect fauna. Velvet ants (Hymenoptera: Mutillidae) are common in these deserts. Velvet ants are important to ecosystem health, particularly in desert environments, because they are parasitic on the bees and wasps that help maintain overall ecosystem function. The goal of this study was to measure velvet ant diversity across the deserts of southern California. We made preliminary collections from 10 sites in a variety of areas in the western Sonoran Desert (Colorado Desert), the Mojave Desert, and the Great Basin Desert. We measured β-diversity using Sørensen’s similarity index to compare velvet ant richness and relative abundance between different sites. To determine how accurate our similarity estimates were, and to gain an understanding of actual velvet ant diversity, we also compared velvet ant richness of 2 sites (Algodones Sand Dunes and Deep Canyon) using data obtained from the examination of museum specimens borrowed from over 12 museums across the West. Comparisons of velvet ant faunas between sites revealed low similarities (0.167–0.75 species richness only; 0.022–0.67 both abundance and richness). Low similarity values indicate that a rich velvet ant fauna exists in the deserts of southern California.     

The draft genome of the parasitic nematode Trichinella spiralis

Genome evolution studies for the phylum Nematoda have been limited by focusing on comparisons involving Caenorhabditis elegans. We report a draft genome sequence of Trichinella spiralis, a food-borne zoonotic parasite, which is the most common cause of human trichinellosis. This parasitic nematode is an extant member of a clade that diverged early in the evolution of the phylum, enabling identification of archetypical genes and molecular signatures exclusive to nematodes. We sequenced the 64-Mb nuclear genome, which is estimated to contain 15,808 protein-coding genes, at ～35-fold coverage using whole-genome shotgun and hierarchal map-assisted sequencing. Comparative genome analyses support intrachromosomal rearrangements across the phylum, disproportionate numbers of protein family deaths over births in parasitic compared to a non-parasitic nematode and a preponderance of gene-loss and -gain events in nematodes relative to Drosophila melanogaster. This genome sequence and the identified pan-phylum characteristics will contribute to genome evolution studies of Nematoda as well as strategies to combat global parasites of humans, food animals and crops.     

Understanding recent trends in marriage

This article explores recent trends in marriage. Following consistent falls in marriage rates in the last quarter of the 20th century the early years of this century have seen some relatively large fluctuations in marriage numbers and rates. This article illustrates some of the recent trends in marriage. One innovation is that it presents marriage data by month, controlled for the effect of peak marriage days in the week. It also discusses a recent legislative change, affecting those subject to immigration control that wish to marry, which may be one of many factors affecting latest marriage trends. Readers should bear in mind that the 2005 data shown in the article are provisional.     

The never-ending story of peptide O-xylosyltransferase

In a journey lasting 40 years from the first reports on its activity in the 1960s to its purification and the cloning of relevant complementary DNAs, peptide O-xylosyltransferase has finally arrived at the same point as many other enzymes. This enzyme, whose systematic name is UDP--D-xylose:proteoglycan core protein -D-xylosyltransferase (EC 2.4.2.26), catalyses the first step in the biosynthesis of chondroitin, dermatan and heparan sulphates in the endoplasmic reticulum and/or the cis-Golgi cisternae. Analyses of their primary structure show that peptide O-xylosyltransferases are members of glycosyltransferase family 14 and so are homologous to 1,6-N-acetylglucosaminyltransferases involved in O-glycan and poly-N-acetyllactosamine branching. Furthermore, vertebrates appear to have two rather similar genes encoding xylosyltransferase I and xylosyltransferase II, but enzymatic activity was only detected for a recombinant form of the first isoform. On the other hand, Caenorhabditis and Drosophila have each only one peptide O-xylosyltransferase gene. In the worm sqv-6 mutant, a mutation of the xylosyltransferase gene is associated with defective vulval morphogenesis, indicative of the importance of the glycosaminoglycan chains of proteoglycans in animal development. There remain, however, open questions, for instance, on the enzymes intracellular localisation and structure-function relationships.Received 11 July 2003; received after revision 4 September 2003; accepted 24 September 2003