Biomedical subjects

Oliver Attie

Publications and source records attributed to Oliver Attie.

4 recordsLinked to original sources

PubMed2006

Co-evolution of the outer surface protein C gene (ospC) and intraspecific lineages of Borrelia burgdorferi sensu stricto in the northeastern United States.

Clinical and tick isolates of Borrelia burgdorferi sensu stricto, the bacterial agent of Lyme disease, from the northeastern United States were sequenced at 12 loci located on the main chromosome and 7 plasmids (lp54, cp26, cp9, lp17, lp25, lp28-2, and lp38). The outer surface protein C gene (ospC) showed the highest number (12) of major alleles (defined as alleles differing by 5% or more in nucleotide sequence) while other ORFs had only two to four major alleles. A non-recombining chromosomal marker, the rrs-rrlA ribosomal RNA spacer, was used to infer the intraspecific phylogeny among these B. burgdorferi isolates. We were thus able to analyze the multilocus genotypes in the context of a B. burgdorferi intraspecific phylogeny. Except for ospC, sequence variations at plasmid-borne loci showed broad inconsistency with the intraspecific phylogeny, supporting DNA exchanges mediated by plasmid transfers. The multilocus linkage frequently observed in B. burgdorferi populations is due more likely to a "founder effect" than to a lack of recombination. The exceptional phylogenetic consistency of ospC, in conjunction with its selectively maintained high intraspecific diversity, suggested a dominant role ospC plays in the initiation and maintenance of adaptive differentiation in B. burgdorferi.

Antigens, Bacterial↗

PubMed2006

Composition-modified matrices improve identification of homologs of saccharomyces cerevisiae low-complexity glycoproteins.

Yeast glycoproteins are representative of low-complexity sequences, those sequences rich in a few types of amino acids. Low-complexity protein sequences comprise more than 10% of the proteome but are poorly aligned by existing methods. Under default conditions, BLAST and FASTA use the scoring matrix BLOSUM62, which is optimized for sequences with diverse amino acid compositions. Because low-complexity sequences are rich in a few amino acids, these tools tend to align the most common residues in nonhomologous positions, thereby generating anomalously high scores, deviations from the expected extreme value distribution, and small e values. This anomalous scoring prevents BLOSUM62-based BLAST and FASTA from identifying correct homologs for proteins with low-complexity sequences, including Saccharomyces cerevisiae wall proteins. We have devised and empirically tested scoring matrices that compensate for the overrepresentation of some amino acids in any query sequence in different ways. These matrices were tested for sensitivity in finding true homologs, discrimination against nonhomologous and random sequences, conformance to the extreme value distribution, and accuracy of e values. Of the tested matrices, the two best matrices (called E and gtQ) gave reliable alignments in BLAST and FASTA searches, identified a consistent set of paralogs of the yeast cell wall test set proteins, and improved the consistency of secondary structure predictions for cell wall proteins.

Algorithms↗

PubMed2005

Efficient sorting of genomic permutations by translocation, inversion and block interchange.

MOTIVATION: Finding genomic distance based on gene order is a classic problem in genome rearrangements. Efficient exact algorithms for genomic distances based on inversions and/or translocations have been found but are complicated by special cases, rare in simulations and empirical data. We seek a universal operation underlying a more inclusive set of evolutionary operations and yielding a tractable genomic distance with simple mathematical form. RESULTS: We study a universal double-cut-and-join operation that accounts for inversions, translocations, fissions and fusions, but also produces circular intermediates which can be reabsorbed. The genomic distance, computable in linear time, is given by the number of breakpoints minus the number of cycles (b-c) in the comparison graph of the two genomes; the number of hurdles does not enter into it. Without changing the formula, we can replace generation and re-absorption of a circular intermediate by a generalized transposition, equivalent to a block interchange, with weight two. Our simple algorithm converts one multi-linear chromosome genome to another in the minimum distance.

Algorithms↗

PubMed2004

Genetic exchange and plasmid transfers in Borrelia burgdorferi sensu stricto revealed by three-way genome comparisons and multilocus sequence typing.

Comparative genomics of closely related bacterial isolates is a powerful method for uncovering virulence and other important genome elements. We determined draft sequences (8-fold coverage) of the genomes of strains JD1 and N40 of Borrelia burgdorferi sensu stricto, the causative agent of Lyme disease, and we compared the predicted genes from the two genomes with those from the previously sequenced B31 genome. The three genomes are closely related and are evolutionarily approximately equidistant ( approximately 0.5% pairwise nucleotide differences on the main chromosome). We used a Poisson model of nucleotide substitution to screen for genes with elevated levels of nucleotide polymorphisms. The three-way genome comparison allowed distinction between polymorphisms introduced by mutations and those introduced by recombination using the method of phylogenetic partitioning. Tests for recombination suggested that patches of high-density nucleotide polymorphisms on the chromosome and plasmids arise by DNA exchange. The role of recombination as the main mechanism driving B. burgdorferi diversification was confirmed by multilocus sequence typing of 18 clinical isolates at 18 polymorphic loci. A strong linkage between the multilocus sequence genotypes and the major alleles of outer-surface protein C (ospC) suggested that balancing selection at ospC is a dominant force maintaining B. burgdorferi diversity in local populations. We conclude that B. burgdorferi undergoes genome-wide genetic exchange, including plasmid transfers, and previous reports of its clonality are artifacts from the use of geographically and ecological isolated samples. Frequent recombination implies a potential for rapid adaptive evolution and a possible polygenic basis of B. burgdorferi pathogenicity.

Amino Acid Sequence↗