Too much of a good thing: mechanisms of gene action in Down syndrome

The molecular mechanisms underlying the specific traits in individuals with Down syndrome (DS) have been postulated to derive either from nonspecific perturbation of balanced genetic programs, or from the simple, mendelian-like influence of a small subset of genes on chromosome 21. However, these models do not provide a comprehensive explanation for experimental or clinical observations of the effects of trisomy 21. DS is best viewed as a complex genetic disorder, where the specific phenotypic manifestations in a given individual are products of genetic, environmental and stochastic influences. Mouse models that recapitulate both the genetic basis for and the phenotypic consequences of trisomy provide an experimental system to define these contributions.     

XREFdb: cross-referencing the genetics and genes of mammals and model organisms

XREFdb supports the investigation of protein function in the context of information available through work in multiple organisms. In addition to facilitating the association of functional data among known genes from multiple organisms, XREFdb has developed strategies that provide access to information associated with as-yet unstudied genes. The database organizes protein similarity and genetic map positional information from diverse sources in the public domain to facilitate investigator evaluation of potential functional significance. XREFdb is found at URL www.ncbi.nlm.nih.gov/XREFdb     

The colanic acid gene cluster of Salmonella enterica has a complex history

The colanic acid gene cluster of Salmonella enterica LT2 was sequenced and compared with that of Escherichia coli K-12. The two clusters are similar with divergence slightly higher than average for genes of the two species. The cluster was divided into four blocks by GC content and seems likely to have transferred from a higher GC content species to the ancestor of E. coli and S. enterica. All 19 genes of K-12 and 13 genes of LT2 appear to have undergone random genetic drift with amelioration of the GC content. However, in the case of S. enterica, we believe that the six genes of the GDP-fucose pathway group were replaced relatively recently by genes closely related to those of the original donor species. Two repetitive elements were observed: a bacterial interspersed mosaic element in the intergenic region between wzx and wcaK in K-12 only and a RSA (repetitive sequence element) sequence between wcaJ and wzx in LT2 only.     

Variation of the Ribosomal Operon 16S-23S Gene Spacer Region in Representatives of Salmonella enterica Subspecies

The 16S-23S spacer regions of two ribosomal operons (rrnA and rrnE) have been sequenced in seven representatives of the Salmonella enterica subspecies. Isolated nucleotide substitutions were found at the same sites as in Escherichia coli but the number of polymorphic sites was much larger, as could be expected for a more heterogeneous species. Still, as in E. coli, most of the variation found was due to insertions and/or deletions affecting blocks of nucleotides generally located at equivalent regions of the putative secondary structure for both species. Isolated polymorphic sites generated phylogenetic trees generally consistent with the subspecies structure and the accepted relationships among the subspecies. However, the sequences of rrnE put subspecies I closer to E. coli K-12 than to the other S. enterica subspecies. The distribution of polymorphisms affecting blocks of nucleotides was much more random, and the presence of equivalent sequences in distantly related subspecies, and even in E. coli, could reflect relatively frequent horizontal transfer. The smallest 16S-23S spacers in other genera of the family Enterobacteriaceae were also sequenced. As expected, the level of variation was much larger. Still, the phylogenetic tree inferred is consistent with those of 16S rRNA or housekeeping genes.     

Escherichia coli Clone Sonnei (Shigella sonnei) Had a Chromosomal O-Antigen Gene Cluster Prior to Gaining Its Current Plasmid-Borne O-Antigen Genes

O antigen is part of the lipopolysaccharide present in the outer membrane of gram-negative bacteria. The surface-exposed O antigen is subject to selection by the host immune system, which may account for the maintenance of many different O-antigen forms. Characteristically, all genes specific to O-antigen synthesis are clustered in a region close to the his and gnd genes on the chromosome of Escherichia coli and related species. Shigella sonnei, essentially a clone of E. coli (E. coli clone Sonnei), is an important human pathogen and is unusual in that its O-antigen gene cluster is located on a plasmid. Our results suggest that it once had a normal chromosomal O-antigen gene cluster which has been largely deleted. We suggest that the O antigen encoded by the plasmid-borne genes offered a selective advantage in adapting to a new environment and that the chromosomal O-antigen genes were eventually inactivated. We also identified, by PCR and sequencing, a potential ancestor of E. coli Sonnei among the 166 known E. coli serotype strains.