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Biomedical subjects

J F Peden

Publications and source records attributed to J F Peden.

5 recordsLinked to original sources

Complete genome sequence of Neisseria meningitidis serogroup B strain MC58.

The 2,272,351-base pair genome of Neisseria meningitidis strain MC58 (serogroup B), a causative agent of meningitis and septicemia, contains 2158 predicted coding regions, 1158 (53.7%) of which were assigned a biological role. Three major islands of horizontal DNA transfer were identified; two of these contain genes encoding proteins involved in pathogenicity, and the third island contains coding sequences only for hypothetical proteins. Insights into the commensal and virulence behavior of N. meningitidis can be gleaned from the genome, in which sequences for structural proteins of the pilus are clustered and several coding regions unique to serogroup B capsular polysaccharide synthesis can be identified. Finally, N. meningitidis contains more genes that undergo phase variation than any pathogen studied to date, a mechanism that controls their expression and contributes to the evasion of the host immune system.

Antigenic Variation

Simple sequence repeats in the Helicobacter pylori genome.

We describe an integrated system for the analysis of DNA sequence motifs within complete bacterial genome sequences. This system is based around ACeDB, a genome database with an integrated graphical user interface; we identify and display motifs in the context of genetic, sequence and bibliographic data. Tomb et aL (1997) previously reported the identification of contingency genes in Helicobacter pylori through their association with homopolymeric tracts and dinucleotide repeats. With this as a starting point, we validated the system by a search for this type of repeat and used the contextual information to assess the likelihood that they mediate phase variation in the associated open reading frames (ORFs). We found all of the repeats previously described, and identified 27 putative phase-variable genes (including 17 previously described). These could be divided into three groups: lipopolysaccharide (LPS) biosynthesis, cell-surface-associated proteins and DNA restriction/modification systems. Five of the putative genes did not have obvious homologues in any of the public domain sequence databases. The reading frame of some ORFs was disrupted by the presence of the repeats, including the alpha(1-2) fucosyltransferase gene, necessary for the synthesis of the Lewis Y epitope. An additional benefit of this approach is that the results of each search can be analysed further and compared with those from other genomes. This revealed that H. pylori has an unusually high frequency of homopurine:homopyrimidine repeats suggesting mechanistic biases that favour their presence and instability.

Base Sequence

DNA sequence evolution: the sounds of silence.

Silent sites (positions that can undergo synonymous substitutions) in protein-coding genes can illuminate two evolutionary processes. First, despite being silent, they may be subject to natural selection. Among eukaryotes this is exemplified by yeast, where synonymous codon usage patterns are shaped by selection for particular codons that are more efficiently and/or accurately translated by the most abundant tRNAs; codon usage across the genome, and the abundance of different tRNA species, are highly co-adapted. Second, in the absence of selection, silent sites reveal underlying mutational patterns. Codon usage varies enormously among human genes, and yet silent sites do not appear to be influenced by natural selection, suggesting that mutation patterns vary among regions of the genome. At first, the yeast and human genomes were thought to reflect a dichotomy between unicellular and multicellular organisms. However, it now appears that natural selection shapes codon usage in some multicellular species (e.g. Drosophila and Caenorhabditis), and that regional variations in mutation biases occur in yeast. Silent sites (in serine codons) also provide evidence for mutational events changing adjacent nucleotides simultaneously.

Animals